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International Journal of Nanomedicine logoLink to International Journal of Nanomedicine
. 2018 Apr 17;13:2321–2336. doi: 10.2147/IJN.S164355

Global trends in nanomedicine research on triple negative breast cancer: a bibliometric analysis

Ramon Handerson Gomes Teles 1, Herick Fernando Moralles 2, Márcia Regina Cominetti 1,✉
PMCID: PMC5910795  PMID: 29713164

Abstract

Nanotechnology has emerged as a promising tool in the clinic to combat several difficult-to-manage diseases, such as cancer, which is the second leading cause of death worldwide. Chemotherapeutic drugs present several limitations such as undesired side effects, low specificity, resistance, and high relapse rates. Triple negative breast cancer (TNBC) is caused by cells that lack specific receptors in their membrane, such as estrogen (ER+) and progesterone (PR+) receptors, or by cells that do not express the amplification of human epidermal growth factor receptor-2 (HER-2+). This cancer type has poor prognosis, high relapse rates, and no targeted therapies. Thus, this study aimed to investigate the trends of nanotechnology research in TNBC and compare the contribution of research from different regions, institutions, and authors. A search of the studies published between 2012 and 2017, related to nanotechnology and TNBC, with different keyword combinations, was performed in the Scopus database. The keywords found in this search were grouped into four clusters, in which “breast cancer” was the most mentioned (1,133 times) and the word “MCF-7 cell line” is one of the latest hotspots that appeared in the year 2016. A total of 1,932 articles, which were cited 26,450 times, were identified. The USA accounted for 28.36% of the articles and 27.61% of the citations; however, none of its centers appeared in the list of 10 most productive ones in terms of publications. The journals Biomaterials and International Journal of Nanomedicine had the highest number of publications. The USA and China had the highest number of articles produced and cited; however, the highest average citation per article was from Singapore. The studies focused on the research of antineoplastic agents in animal models and cell culture, and these were the most used topics in research with nanotechnology and TNBC.

Keywords: oncology, breast cancer, nanotechnology, nanomedicine, bibliometric

Introduction

Cancer is a term that refers to the rapid growth and division of abnormal cells in a part of the body.1 These cells promote alterations in primary tissue and have the ability to invade different parts of the body and spread to other organs2 originating metastasis, which constitutes a challenge in cancer treatment.3 There are >100 types of cancers, and different risk factors contribute to the development of cancers in different sites.4 Cancer is the second cause of death and its main risk factor is aging. This fact is alarming, since a double of the population older than 65 years is expected to be affected in the next 20 years, increasing from 616 million to 1,157 billion worldwide.5

The most incident type of cancer is the non-melanoma skin for both sexes, followed by prostate cancer in men and breast cancer in women, which affects women the most worldwide.1 Breast tumors are categorized into three main classes: those in which cells have estrogen receptor (ER+) or progesterone receptor (PR+), those in which cells have human epidermal growth factor receptor-2 (HER-2+) with or without ER+, and the triple negative breast cancer (TNBC) defined by the absence of these receptors.6,7

TNBC affects 9%–16% of the population worldwide, has a poor prognosis related to cure and survival, has high relapse rates, and has no targeted therapies.8 Basically, breast cancer treatment constitutes surgery, chemotherapy, and radiotherapy.9 There is an urgent need for chemotherapeutics that act selectively to inhibit neoplastic cell growth, leaving the non-tumor cells intact.10 However, the majority of the drugs used in chemotherapy are mutagenic and cause damage to DNA from the tumor and non-tumor cells, leading to the death of rapidly dividing cells, which is associated with the collateral effects observed in patients.11

Aiming to improve the efficacy to decrease toxicity and increase the bioavailability of chemotherapy medication, nanotechnology has emerged as an important option.12,13 Nanoparticles accumulate preferentially in the tumors due to the presence of well defined characteristics in tumors mass, such as the defective vasculature and poor lymphatic drainage, resulting in an increase in permeation and retention effect.14,15 For antitumor treatment, nanoparticles may serve as carriers of compounds with higher selectivity for primary tumor and metastases, reducing the drug resistance and side effects.16 In TNBC, gold nanoparticles conjugated with folic acid have shown significantly higher cell entry rates in both in vitro and in vivo models, indicating that folate receptors can be used as targeted therapies for TNBC.17 This pattern was also observed with fructose-coated nanoparticles showing high selectivity (100-fold) for breast cancer cells compared to normal cells.18–20

This review aims to provide an update of the scientific production related to nanoparticles for breast cancer treatment, mainly for the triple negative subtype, during the period between 2012 and 2017.

Materials and methods

Literature search was performed in August 2017 in Scopus database, using the keywords (nanotechnology OR nanomedicine OR nanoparticle OR drug carrier) AND (triple negative breast cancer OR TNBC OR breast cancer), and was confined to articles published in journals related to Biotechnology, Pharmacology, Toxicology and Pharmaceutics, and Medicine areas, published in the period ranging from 2012 to 2017, and written in English language.

The results regarding authors who are publishing in the field were analyzed through tools in Scopus database. Impact factor (IF) of the journals was analyzed using InCites Journal Citation Reports from Thomson Reuters. VOSviewer version 1.6.0 software (Leiden University, Leiden, the Netherlands) was used to analyze the relationship between the most cited references and the most productive authors to generate the map and clusters visualization. STATA software and Microsoft Excel 2013 were used to calculate the cumulative volume and to predict paper trends using polynomial multiple regression models. GraphPad Prism 5 and RSudio 1.1.383 were used to create graphics.

Results

General information

The initial number of identified studies using the keyword combination was 4,676. After exclusions, the final number was 1,932, as demonstrated in the flow chart depicted in Figure 1.

Figure 1.

Figure 1

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Flow chart of studies used in the analysis.

Notes: *Document type includes only the articles published in journals. Conference papers, short surveys, editorials, notes, letters, book chapters, and articles in press were excluded. Source type includes only journals. Conference proceedings, book series, and books were excluded from the results.

In the period ranging from 2012 to 2017, 1,932 papers were published by 7,666 authors on the theme in 425 journals using 14,614 keywords (Table 1). There was a growth in the annual number of papers, from 200 in 2012 to 1,757 in 2016, with a projection of 2,256 for 2017 and 2,798 for 2018. In this period, the increase in the number of publications can be represented by the polynomial regression model: y=21.93 x2−87,939.19x+88,163,841.66, with y being the year and x being the cumulative volume of papers (Figure 2).

Table 1.

General information on articles related to nanotechnology and triple negative breast cancer published in the period from 2012 to 2017

Articles 1,932
Articles per author 0.252
Author per article 3.97
Coauthor per article 6.8
Sources (journals) 425
Keywords 3,966
Authors 7,666
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Figure 2.

Figure 2

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Cumulative volume of articles related to nanotechnology and triple negative breast cancer: global trends for 2030.

For the prediction model, functional specification, linear, logarithmic, polynomial, and exponential equations were tested. Hence, the choice of a second-order polynomial model for Figures 2 and 3A and B was based on the maximization of the R2 goodness-of-fit coefficient of the available historical data, from 2012 to 2017, which served as the basis for choosing the model with the highest R2.

Figure 3.

Figure 3

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Prediction of the number of publications in the field of nanotechnology and triple negative breast cancer expected until 2030 from (A) India, (B) China, and (C) the USA. (D) Quantity of publications related to nanotechnology and triple negative breast cancer by country during the period 2012–2017.

Countries

The most productive country in terms of publication, using the keywords already mentioned, was the USA with 548 papers, representing 28.36% of total publications (Figure 3A). After this, China and India occupied second and third positions, respectively, with 494 (25.56%; Figure 3B) and 257 (13.30%) papers (Figure 3C). The choice of the functional specification for Figure 3A followed the same R2 maximization logic; consequently, for the USA, the best specification was linear. This displays that India, China, and the USA show a growing trend in publications. However, the USA has a steady rate, while India and China are growing at increasing rates; thus, the expectation is that by 2018, China (which has the steepest growth rate) will exceed the USA in the number of publications. The top 10 countries that published more articles from 2012 to 2017 are shown in Figure 3D.

The papers were cited 26,450 times. The citation frequency was 13.69 times per paper. Singapore was the country that had the highest average of article citations (27 times). The number of citations of all papers from the USA was 7,304, comprising 27.61% of the total citations. China was in the second position with 7,126. The top 10 most cited countries are shown in Figure 4.

Figure 4.

Figure 4

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Total and average article citations per country of papers in the area of nanotechnology and triple negative breast cancer during the period 2012–2017.

Institutes

The institute with the largest number of publications and citations in the area of nanotechnology and TNBC during the period was the Chinese Academy of Sciences, with 99 papers and 1,832 citations, comprising 5.12% of the total literature, and being the most cited institute. There are five other Chinese institutes in top 10 of the most cited publications and 2 are from Iran (Table 2). The USA was the country that was the most cited; however, the US institutes do not appear among the top 10 that published the most in the field. The M.D. Anderson Cancer Center from the University of Texas with 25 publications and 693 citations and the Harvard Medical School with 18 publications and 616 citations were the American institutes that published the most in the area.

Table 2.

Main affiliations of authors publishing in the area of nanotechnology and triple negative breast cancer

Institute Documents Citations
Chinese Academy of Sciences 99 1,832
Tehran University of Medical Sciences 56 468
Ministry of Education China 43 460
Sichuan University 38 923
Tabriz University of Medical Sciences 36 256
University of Toronto 32 131
Perking University 29 513
National University of Singapore 28 786
Shenyang Pharmaceutical University 27 427
National Center for Nanoscience and Technology, Beijing 27 489
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Journals

The top 10 journals published 625 papers in the area of TNBC and nanotechnology, comprising 32.34% of the total. Biomaterials (IF 8.402; 2016) had the largest number of publications with 120 papers and was the most cited journal with 4,180 citations, followed by International Journal of Nanomedicine (IF 4.300; 2016) with 113 papers and 1,332 citations and International Journal of Pharmaceutics (IF 3.649; 2016) with 70 documents and 970 citations. The top 10 journals publishing in the area are shown in Table 3.

Table 3.

Top 10 journals published in the area of nanotechnology and triple negative breast cancer

Journal Impact factor (2016) Documents Citations
Biomaterials 8.402 120 4,018
International Journal of Nanomedicine 4.300 113 1,332
International Journal of Pharmaceutics 3.649 70 970
Journal of Controlled Release 7.786 61 1,198
Colloids and Surfaces B Biointerfaces 3.887 61 869
Molecular Pharmaceutics 4.440 60 1,201
Nanomedicine Nanotechnology Biology and Medicine 5.720 36 550
PLoS One 2.806 36 370
Nanomedicine 4.727 34 269
Journal of Biomedical Nanotechnology 4.521 34 322
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Authors, patents, and clinical trials

The top 10 most productive authors had a total of 160 papers, contributing to 8.3% of all publications in the field. In the period ranging from 2012 to 2017, “Li, Yaping” from Shanghai Institute of Materia Medica (China) produced most papers in the area, with 23 articles. His most cited paper is entitled “Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer” (2014) with 56 citations. “Atyabi, F” and “Yu, Hainjun” published 18 articles each. Furthermore, during the same period, >9,000 patents were filed; thus, the patents filed by the 10 authors who published the most were searched. Of these, four authors filed patents. “Ferrari, Mauro” was the most productive with 10 patents. The top 10 authors in this area are shown in Table 4, and a list of their patents is shown in Table 5.

Table 4.

Top 10 authors in the area of nanotechnology and triple negative breast cancer

Author Affiliation Documents (total)
h-Index (total)
Most cited article (total)
Citations of the most cited paper Citations (total) by documents
References
Documents (5 years) h-Index (5 years) Most cited article (5 years) Citations (5 years) by documents
Li, Yaping Shanghai Institute of Materia Medica, Chine Academy of Sciences, State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai, China 174 44 Li Y-P, et al. PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats. J Control Release. 2001;71(2):203–211 336 6,439 by 5,004 21
23 15 Tang S, et al. Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer. Biomaterials. 2014;35(23):6047–6059 56 524 by 490 22
Atyabi, F Tehran University of Medical Sciences, Nanotechnology Research Centre, Tehran, Iran 189 34 Dinarvand R, et al. Polylatide-co-glycolide nanoparticles for controlled delivery of anticancer agents. Int J Nanomed. 2011;6:877–895 154 3,862 by 3,104 23
18 8 Taheri A, et al. The in vivo antitumor activity of LHRH targeted methotrexate-human serum albumin nanoparticles in 4T1 tumor-bearing Balb/c mice. Int J Pharm. 2012;431(1–2):183–189 26 155 by 142 24
Yu, Hainjun Shanghai Institute of Materia Medica, Chinese Academy of Sciences, State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai, China 82 24 Duan X, et al. Smart pH-sensitive and temporal-controlled polymeric micelles for effective combination therapy of doxorubicin and disulfiram. ACS Nano. 2013;7(7):5858–5869 156 1,949 by 1,495 25
18 12 Tang S, et al. Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer. Biomaterials. 2014;35(23):6047–6059 56 437 by 374 22
Zhang, Z Shanghai Institute of Materia Medica, Chinese Academy of Sciences, State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai, China 116 31 He Q, et al. In vivo biodistribution and urinary excretion of mesoporous sílica nanoparticles: effects of particle size PEGylation. Small. 2011;7(2):271–280 262 3,624 by 2,855 26
17 12 Tang S, et al. Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer. Biomaterials. 2014;35(23):6047–6059 56 431 by 368 22
Yin, Qi Shanghai Institute of Materia Medica, Chinese Academy of Sciences, State Key Laboratory of Drug Research, Shanghai, China 69 27 Gao Y, et al. Controlled intracellular release of doxorubicin in multidrug-resistant cancer cells by tuning the shell-pore sizes of mesoporous sílica nanoparticles. ACS Nano. 2011;5(12):9788–9798 197 2,082 by 1,620 27
16 10 Tang S, et al. Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer. Biomaterials. 2014;35(23):6047–6059 56 387 by 338 22
Akbarzadeh, Abolfazl Tabriz University of Medical Sciences, Department of Medical Nanotechnology, Tabriz, Iran 141 25 Akbarzadeh A, et al. Liposome: classification preparation, and applications. Nanoscale Res Lett. 2013;8(1):1–8 295 2,202 by 1,365 28
14 6 Ghasemali S, et al. Inhibitory effects of β-cyclodextrin-helenalin complexes on H-TERT gene expression in the T47D breast cancer cell line – results of real time quantitative PCR. Asian Pac J Cancer Prev. 2013;14(11):6949–6953 36 115 by 94 29
Wang, Wueqing Peking University, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing, China 118 27 Dai J, et al. pH-sensitive nanoparticles for improving the oral bioavailability of cyclosporine A. Int J Pharm. 2004;280(1–2):229–240 123 2,064 by 1,667 30
14 8 Wang Z, et al. The use of a tumor metastasis targeting peptide to deliver doxorubicin-containing liposomes to highly metastatic cancer. Biomaterials. 2012;33(33):8451–8460 64 271 by 250 31
Zhang, Qiang Peking University, State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China 109 22 Zhang Y, et al. The eradication of breast cancer and cancer stem cells using octreotide modified paclitaxel active targeting micelles and salinomycin passive targeting micelles. Biomaterials. 2012;33(2):679–691 104 1,413 by 1,201 32
14 7 Feng Q, et al. Synergistic inhibition of breast cancer by co-delivery of VEGF siRNA and paclitaxel via vapreotide-modified core-shell nanoparticles. Biomaterials. 2014;35(18):5028–5038 57 245 by 234 33
Dinarvand, Rassoul Tehran University of Medical Sciences, Nanotechnology Research Center, Tehran, Iran 294 37 Ganjali MR, et al. Schiff’s bases and crown ethers as supramolecular sensing materials in the construction of potentiometric membrane sensors. Sensors. 2008;8(3):1645–1703 169 5,580 by 4,455 34
13 7 Taheri A, et al. The in vivo antitumor activity of LHRH targeted methotrexate-human serum albumin nanoparticles in 4T1 tumor-bearing Balb/c mice. Int J Pharm. 2012;431(1–2):183–189 26 129 by 123 24
Ferrari, Mauro Methodist Hospital Houston, Department of Nanomedicine, Houston, USA 450 65 Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005;5(3):161–171 2,700 17,952 by 11,803 35
13 10 Xu R, et al. Na injectable nanoparticle generator enhances delivery of cancer therapeutics. Nat Biotechnol. 2016;34(4):414–418 62 336 by 253 36
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Table 5.

Patents filed by the top 10 authors in the area of nanotechnology and triple negative breast cancer

Inventors Patent name Applicant Date of filing Patent office Patent number
Li, Yaping (Pudong Shanghai, CN); Chen, Lingli (Pudong Shanghai, CN); Zheng, Zhaolei (Pudong Shanghai, CN); Zhang, Zhiwen (Pudong Shanghai, CN); Gu, Wangwen (Pudong Shanghai, CN) Irinotecan hydrochloride composite phospholipid composition, preparation method and use thereof Shanghai Institute of Materia Medica, Chinese Academy Sciences
Shanghai Jingfeng Pharmaceutical CO., LTDA		 March 6, 2015 United States Patent and Trademark Office Pre-Granted Publication United Kingdom Patent Application United States Patent and Trademark Office Pre-Granted Publication US20170087146
GB20160016625 20150306
Gillman, Kevin W (Madison, CT); Goodrich, Jason (Wallingford, CT); Boy, Kenneth M (Durham, CT); Zhang, Yunhui (Glastonbury, CT); Mapelli, Claudio (Lawrenceville, NJ); Poss, Michael A (Lawrenceville, NJ); Sun, Li-Qiang (Glastonbury, CT); Zhao, Qian (Wallingford, CT); Mull, Eric (Guilford, CT); Gillis, Eric P (Cheshire, CT); Scola, Paul Michael (Glastonbury, CT) Immunomodulators Bristol-Myers Squibb Company November 11, 2015 US20160137696
Dinarvand, Rassoul (Tehran, IR); Derakhshan, Mohammad Ali (Tehran, IR); Rahbarizadeh, Fatemeh (Tehran, IR); Majidi, Reza Faridi (Tehran, IR); Borujeni, Azade Taheri (Tehran, IR); Rezayat, Seyed Mahdi (Tehran, IR) Multi-mode cancer targeted nanoparticulate system and a method of synthesizing the same Dinarvand; Rassoul
Derakhshan; Mohammad Ali
Rahbarizadeh; Fatemeh
Majidi; Reza Faridi
Borujeni; Azade Taheri
Rezayat; Seyed Mahdi		 January 11, 2012 United States Patent and Trademark Office Pre-Granted Publication US20130178603
Mi, Yu (Houston, TX); Ferrari, Mauro (Houston, TX) Micro/nano composite drug delivery formulations and uses thereof The Methodist Hospital (Houston, TX, USA) August 25, 2016 United States Patent and Trademark Office Pre-Granted Publication US20170056327
Shen, Haifa (Houston, TX); Ferrari, Mauro (Houston, TX); Shen, Jian (Houston, TX); Zhang, Mingzhen (Houston, TX) Polycation-functionalized nanoporous silicon carrier for systemic delivery of gene silencing agents The Methodist Hospital (Houston, TX, USA) December 11, 2015 United States Patent and Trademark Office Pre-Granted Publication US20160369269
Ferrari, Mauro (Houston, TX); Tasciotti, Ennio (Houston, TX); Sakamoto, Jason (Houston, TX) Multistage delivery of active agents Ferrari; Mauro
Tasciotti; Ennio
Sakamoto; Jason		 May 29, 2015 United States Patent and Trademark Office Pre-Granted Publication US20160051481
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We also performed a search on the current scenario of clinical trials in the area of TNBC and nanotechnology using the same combination of keywords described in the section “Materials and methods”. The search resulted in 12 studies (Table 6). One study was excluded since it did not involve nanotechnology. Of the remaining 11 studies, 2 have their results reported. Two of them were related to the use of Abraxane® in a combined regimen with carboplatin or carboplatin and bevacizumab. Abraxane is a nanoparticle containing albumin-bound paclitaxel and bevacizumab in an anti-vascular endothelial growth factor antibody.

Table 6.

Clinical trials in the area of nanotechnology and triple negative breast cancer

Study title Status Interventions First posted Sponsors/collaborators Principal investigators
Carboplatin and paclitaxel albumin-stabilized nanoparticle formulation before surgery in treating patients with locally advanced or inflammatory triple negative breast cancer Recruiting Drug: carboplatin Drug: paclitaxel albumin-stabilized nanoparticle formulation Other: laboratory biomarker analysis February 3, 2012 City of Hope Medical Center National Cancer Institute Yuan Yuan Stephen C Koehler
A trial of nanoparticle albumin-bound paclitaxel (nab-paclitaxel, abraxane®) with or without mifepristone for advanced, glucocorticoid receptor-positive, triple negative breast cancer Recruiting Drug: mifepristone
Other: placebo
Drug: nab-paclitaxel		 June 2, 2016 University of Chicago Rita Nanda
Gini Fleming
Study to evaluate CORT125134 in combination with nab-paclitaxel in patients with solid tumors Recruiting Drug: CORT125134 with nab-paclitaxel May 5, 2016 Corcept Therapeutics Thaddeus S Block
Paclitaxel albumin-stabilized nanoparticle formulation and bevacizumab followed by bevacizumab and erlotinib hydrochloride in treating patients with metastatic breast cancer Active, not recruiting Drug: paclitaxel albumin-stabilized nanoparticle formulation
Biologic: bevacizumab
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis		 August 13, 2008 National Cancer Institute University of Washington Jennifer Specht
Paclitaxel albumin-stabilized nanoparticle formulation in treating older patients with locally advanced or metastatic breast cancer Active, not recruiting Drug: paclitaxel albumin-stabilized nanoparticle formulation Other: questionnaire administration November 1, 2011 National Cancer Institute City of Hope Medical Center Arti Hurria
Veliparib in treating patients with malignant solid tumors that do not respond to previous therapy Active, not recruiting Other: laboratory biomarker analysis
Other: pharmacologic study
Drug: veliparib		 May 4, 2009 National Cancer Institute Shannon Puhalla
Neoadjuvant pembrolizumab(Pbr)/Nab-paclitaxel followed by pbr/epirubicin/cyclophosphamide in TNBC Not yet recruiting Drug: pembrolizumab
Drug: nab-paclitaxel
Drug: epirubicin
Drug: cyclophosphamide		 September 21, 2017 Merck Sharp & Dohme Corp.
Celgene Corporation
Institut fuer Frauengesundheit		 Peter A Fasching
Phase II study with abraxane, bevacizumab and carboplatin in triple negative metastatic breast cancer Completed* Drug: abraxane
Drug: bevacizumab
Drug: carboplatin		 May 28, 2007 Duke University Genentech, Inc.
Celgene Corporation		 Kimberly Blackwell
AZD2281 plus carboplatin to treat breast and ovarian cancer Completed Drug: AZ2281+carboplatin October 3, 2011 National Cancer Institute Jung-Min Lee
An efficacy study of trabectedin in the treatment of participants with specific subtypes of metastatic breast cancer Completed Drug: dexamethasone Drug: trabectedin December 24, 2007 Johnson & Johnson Pharmaceutical Research and Development, LLC PharmaMar Not mentioned
Study of abraxane and carboplatin as first-line treatment for triple negative metastatic breast cancer Terminated* Drug: abraxane Drug: carboplatin September 22, 2010 Duke University
Celgene Corporation		 Kimberly L Blackwell
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Note:

*

Studies that have results.

The results regarding the safety and tolerability for the clinical trial using Abraxane and carboplatin were not presented, according to the report provided, due to insufficient accrual for the study. However, 60% of patients (6/10) presented serious adverse effects, such as anemia, alterations in neutrophil count, gastrointestinal disorders, and allergic reactions, after treatment. All the patients (10/10) had other adverse effects such as nausea, edema, and pain. This study was terminated.

The study using Abraxane with carboplatin and bevacizumab involved 41 women with TNBC in stage IV or inoperable stage III. Results of 39 patients were provided. Of them, 18% had complete response, 69% had partial response, 8% presented stable disease, and only 5% had progressive disease. The duration of progression-free disease was 15 months; however, 53.66% and 100% of the participants had serious adverse effects and other adverse effects, respectively.

Overall, the scenario on TNBC and nanotechnology is not greatly encouraging currently. As in traditional chemotherapy, adverse effects of the regimens seem to be the main cause of concern. Notwithstanding, further research and the introduction of different nanosystems are pivotal for the improvement of therapeutic options for TNBC.

Articles

The top 10 most cited articles had 2,224 citations, representing 8.4% of the total citations. The paper entitled “Preclinical development and clinical translation of PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile” (2012) published in Science Translational Medicine by HrKach J et al was the most cited, with 445 citations. The top 10 most cited articles are shown in Table 7.

Table 7.

Top 10 cited papers in the area of nanotechnology and triple negative breast cancer

Authors and journal Article Main results Total citations Average citations per year References
Hrkach J, et al. Science Translational Medicine. 2012;4(128):128ra39 Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile Docetaxel encapsulated in polymeric nanoparticle exhibited enhanced tumor accumulation and prolonged tumor growth suppression in low doses also, compared to that typically used in the clinic 445 88.2 37
Ohno S-I, et al. Molecular Therapy. 2013;21(1):185–191 Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells Exosomes can efficiently deliver miRNA to EGFR-expressing breast cancer cells, also can be used therapeutically to target EGFR- expressing cancerous tissues with acid drugs 291 70.5 38
Danhier F, Breton AL, Préat V. Molecular Pharmaceutics. 2012;9(11):2961–2973 RGD-based strategies to target alpha(v) beta (3) integrin in cancer therapy and diagnosis This review aims to highlight the position of RGD-based nanoparticles in cancer therapy and imaging 283 55.4 39
Ge J, et al. Nature Communications. 2014;5:4596 A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation Graphene quantum dots can be used as photodynamic agents allowing imaging and providing a highly efficient cancer therapy 219 71.7 40
Yuan H, Fales AM, Vo-Dinh T. Journal of the American Chemical Society. 2012;134(28):11358–11361 TAT peptide-functionalized gild nanostars: enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance The entrance of TAT-peptide-functionalized gold nanostars in the cells is increased after photothermolysis, enhancing its intracellular delivery and action 212 41.4 41
Cheng L, et al. Biomaterials. 2012;33(7):2215–2222 Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy Multifunctional nanoparticles under application of near-infrared laser irradiation promotes photothermal therapeutic efficacy with 100% tumor elimination in in vivo model 208 41.4 42
King HW, Michael MZ, Gleadle JM. BMC Cancer. 2012;12:421 Hypoxic enhancement of exosome release by breast cancer cells Hypoxia promotes the release of exosomes by breast cancer cells mediated by HIF-1α 166 32.4 43
Amoozgar Z, Yeo T. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2012;4(2):219–233 Recent advances in stealth coating of nanoparticle drug delivery systems This review aims to disseminate strategies to improve the action of nanoparticles using different synthesis methods and to present general characteristics about it 156 31.0 44
Pecot CV, et al. Nature Communications. 2013;4:2427 Tumour angiogenesis regulation by the miR-200 family miR-200 inhibits angiogenesis in several cancer types through direct and indirect mechanisms by targeting interleukin-8 and CXCl1 secreted by tumor endothelial and cancer cells 126 31.2 45
She W, et al. Biomaterials. 2013;34(9):2252–2264 Dendronized heparin-doxorubicin conjugate-based nanoparticle as pH-responsive drug delivery system for cancer therapy The nanoparticles were shown to effectively kill cancer cells in vitro, showed strong antitumor activity, showed high antiangiogenesis effects, and induced apoptosis in vivo 118 29.0 46
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Abbreviation: HIF, hypoxia-inducible factor.

Hotspots

Keywords of 1,932 articles were analyzed in VOSviewer. Of 14,614 keywords, 145 were used >85 times in titles and abstracts of all papers. Keywords were classified into four clusters formed in the software VOSviewer: “Drugs”, “Animal Models”, “Human cell lines”, and “Properties”. In the cluster “Drugs”, the most used keywords were “breast cancer” (1,133 times), “drug delivery system” (666 times), and “antineoplasic agent” (544 times).

In the cluster “Animal Models”, the most used keywords were “unclassified drug” (685 times), “in vitro study” (584 times), and “particle size” (551 times). In the cluster “Human cell lines”, the more frequently used keywords were “human” (1,481 times), “humans” (1,340 times), and “chemistry” (855 times). In the cluster “Properties”, the most common keywords were “female” (1,023 times), “nonhuman” (802 times), and “animals” (793 times). Keywords and association lines are shown in Figure 5 and listed in Table S1.

Figure 5.

Figure 5

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Association line of keywords from papers in the area of nanotechnology and triple negative breast cancer.

Several drugs are used in TNBC treatment, and results of clinical studies demonstrated that TNBC patients have different responses to them.47 However, the chemotherapeutic drug widely reported in nanomedicine for the treatment of TNBC was “doxorubicin” (395 times), and the most common carrier nanosystem was “liposome/liposomes” (279 times). Accordingly, during the past few years, various nanomaterials have been developed for the detection and treatment of breast cancer. These nanoparticles are made up of a variety of materials including lipids, polymers, silica, protein/peptides, oligonucleotides, and metals such as gold, silver, and iron.48 We found in this review that the main materials used in the formulations were “macrogol” (191 times), “macrogol derivate” (177 times), and “polyethylene glycols” (265 times).

VOSviewer applied colors to keywords based on the year that they appeared in the literature. Keywords in red appeared early, followed by yellow and green colors, while keywords in blue appeared later. The average year of cluster appearance was close to each other. The cluster “Drugs” had the more recently used keyword “antineoplasic agent” (544 times cited, year of appearance 2014). The cluster “Animal models” had “Breast cancer cell lines” (231 times cited, 2015), the cluster “Human cell lines” had “MCF-7 cell lines” (165 times cited, 2016), and the cluster “Properties” had “Bagg albino mouse” (193 times cited, 2015) as the more recently used keywords (Figure 6). The density map shows the citation concentration areas for keywords (Figure 7).

Figure 6.

Figure 6

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Average year map of keywords.

Figure 7.

Figure 7

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Density map of keywords.

Conclusion

Nanotechnology cancer field has the potential for improving therapeutic efficacy, creating methods for detection, and targeting different cancer stages. Development of various nanomaterials and nanotechnology had allowed the improvement of cancer biomarkers area with high precision and sensibility that was not the case some years ago. In this study, the global scientific production from the period ranging from 2012 to 2017 related to the nanotechnology applied to TNBC research was analyzed quantitatively and qualitatively. Results showed an increase in the cumulative volume of papers worldwide and a tendency to continue growing in terms of publication numbers. Research has focused on the search for drug carrier systems for the treatment of breast cancer in in vitro studies using the MCF-7 cell line and animal models, specifically Bagg albino mouse. Thus, through the study of the quantitative aspects of the production and dissemination of the knowledge generated in the time interval observed through bibliometric analysis, it was possible to trace the research profiles of different countries, centers, and researchers, offering an important analysis of the scientific production, behavior, and development in this field of research.

Supplementary material

Table S1.

List of keywords generated by VOSviewer

Id Cluster Links Total link strength Ocurrences Avg. pub. year
Antibiotics, antineoplasic 1 142 2,748 91 2014.32
Antineoplasic agent 1 145 15,216 544 2014.86
Antineoplastic agents 1 145 12,789 466 2014.52
Antineoplastic agents, phytogenic 1 144 3,049 110 2014.37
Breast cancer 1 145 25,473 1,133 2014.20
Cancer 1 145 2,299 111 2014.31
Cancer chemotherapy 1 145 3,622 135 2014.11
Cancer therapy 1 145 3,606 150 2014.02
Chemistry, pharmaceutical 1 140 2,597 89 2014.53
Chemotherapy 1 145 3,395 132 2014.67
Docetaxel 1 142 3,174 128 2014.39
Doxorubicin 1 145 10,337 395 2014.38
Drug carrier 1 145 12,086 427 2014.87
Drug carriers 1 145 13,199 478 2014.49
Drug delivery 1 145 5,533 226 2014.32
Drug delivery system 1 145 17,825 666 2014.43
Drug delivery systems 1 145 8,691 318 2014.51
Drug efficacy 1 145 8,873 299 2014.26
Drug formulation 1 145 6,652 237 2014.35
Drug resistance 1 145 2,946 93 2014.90
Drug resistance, neoplasm 1 145 3,199 110 2014.90
Drug safety 1 137 2,056 85 2014.24
Drug targeting 1 145 3,707 137 2014.07
Encapsulation 1 142 2,966 104 2014.22
Epidermal growth receptor 2 1 145 2,759 129 2014.37
Liposome 1 145 3,933 165 2014.10
Liposomes 1 144 2,916 114 2014.18
Macrogol 1 145 5,495 191 2014.18
Macrogol derivate 1 144 5,737 177 2015.06
Micelle 1 145 4,475 149 2014.53
Micelles 1 144 4,104 137 2014.53
Molecularly targeted therapy 1 145 2,453 86 2014.37
Multigrud resistance 1 144 2,708 93 2014.69
Nanocarrier 1 145 5,136 179 2014.50
Nanomedicine 1 145 4,366 179 2014.36
Nanotechnology 1 145 3,660 200 2014.15
Neoplasms 1 145 4,503 198 2014.15
Paclitaxel 1 145 6,411 277 2014.26
Polyethylene glycols 1 145 7,772 265 2014.51
Polymer 1 145 4,412 163 2014.44
Polymers 1 145 4,078 149 2014.62
Antineoplastic activity 2 145 12,103 411 2014.35
Biocompatibility 2 145 3,250 129 2014.44
Breast cancer cell line 2 144 6,465 231 2015.23
Cancer cell 2 145 6,297 267 2013.88
Cancer cell culture 2 143 3,361 150 2013.12
Cell strain MCF-7 2 141 1,972 90 2012.83
Cell survival 2 145 9,525 352 2014.43
Cell viability 2 145 7,251 267 2014.50
Chitosan 2 144 2,019 91 2014.87
Concentration response 2 145 2,310 86 2014.05
Confocal microscopy 2 144 2,658 99 2014.35
Cytotoxicity 2 145 10,253 406 2014.37
Drug conjugation 2 145 3,059 103 2014.53
Drug cytotoxicity 2 145 5,914 204 2014.47
Drug release 2 145 9,809 338 2014.57
Drug stability 2 145 3,688 135 2014.22
Drug synthesis 2 145 3,459 132 2014.37
Drug uptake 2 145 3,290 109 2014.45
Endocytosis 2 145 3,664 125 2014.46
Flow cytometry 2 145 4,128 158 2914.37
Fluorescence microscopy 2 145 2,217 89 2014.13
Human cell 2 145 20,170 787 2014.32
Hydrogen ion concentration 2 145 2,670 89 2014.37
IC50 2 143 3,263 103 2015.41
In vitro study 2 145 16,554 584 2014.39
Infrared spectroscopy 2 143 2,917 122 2014.70
Internalization 2 145 3,244 112 2014.53
Nanoencapsulation 2 145 5,072 175 2014.21
Particle size 2 145 14,569 551 2014.48
pH 2 145 4,373 154 2014.63
Physical chemistry 2 145 2,814 103 2014.48
Polyglactin 2 145 2,349 87 2014.11
Scanning electron microscopy 2 144 2,429 111 2014.59
Surface property 2 145 2,998 113 2014.47
Synthesis 2 145 3,766 138 2014.72
Transmission electron microscopy 2 145 5,382 227 2014.34
Unclassified drug 2 145 16,929 685 2014.13
Zeta potential 2 145 6,990 253 2014.44
Apoptosis 3 145 9,513 354 2014.65
Breast cancer cells 3 145 2,200 105 2014.30
Breast neoplasms 3 145 18,161 729 2014.37
Breast tumor 3 145 4,316 182 2014.31
Cell culture 3 145 3,973 169 2014.63
Cell death 3 145 5,057 193 2014.63
Cell line, tumor 3 145 21,152 814 2014.33
Cell proliferation 3 145 6,910 263 2014.48
Cells 3 145 5,212 226 2914.90
Chemistry 3 145 22,331 855 2015.02
Cytology 3 145 4,356 187 2015.14
Diseases 3 145 9,406 400 2014.87
Dose response 3 145 2,356 87 2014.91
Drug effects 3 145 15,154 527 2015.11
Gene expression 3 142 2,240 96 2014.54
Genetics 3 145 4,557 178 2014.98
Gold 3 143 3,108 161 2014.73
Gold nanoparticle 3 144 2,840 148 2014.28
Human 3 145 33,652 1,481 2014.47
Humans 3 145 31,754 1,340 2014.39
MCF-7 cell line 3 145 8,507 308 2014.82
MCF-7 cell lines 3 143 4,219 165 2016.04
MCF-7 cells 3 145 10,907 419 2014.75
Metabolism 3 145 13,700 530 2014.99
Metal nanoparticle 3 144 2,822 146 2014.90
Metal nanoparticles 3 143 3,623 191 2014.61
Nanoparticle 3 145 20,739 856 2014.54
Nanoparticles 3 145 21,557 918 2014.55
Pathology 3 145 12,505 474 2014.92
Procedures 3 145 9,188 368 2015.16
Protein expression 3 145 5,090 200 2014.33
RNA, small interfering 3 143 2,303 86 2014.43
Small interfering RNA 3 145 2,952 120 2014.33
Tumor cell line 3 145 16,200 584 2014.95
Ultrastructure 3 144 3,356 129 2015.16
Animal 4 145 16,923 563 2014.90
Animal cell 4 145 7,522 262 2014.27
Animal experimente 4 145 17,049 571 2014.31
Animal model 4 145 15,890 524 2014.33
Animal tissue 4 145 8,724 293 2014.27
Animals 4 145 22,161 793 2014.29
Bagg albino mouse 4 145 6,713 193 2015.00
Cancer inhibition 4 145 7,263 231 2014.35
Drug distribuition 4 145 5,077 157 2014.28
Drug screening 4 145 5,716 180 2014.83
Female 4 145 25,711 1,023 2014.41
In vivo study 4 145 11,108 360 2014.31
Magnetic resonance imaging 4 142 2,176 87
Magnetite nanoparticle 4 144 2,027 90 2014.50
Magnetite nanoparticles 4 142 2,119 95 2014.35
Male 4 145 4,262 151 2014.26
Mice 4 145 14,860 517 2014.18
Mice, inbred balb c 4 145 8,385 256 2014.44
Mice, nude 4 145 6,470 194 2014.43
Mouse 4 145 19,679 679 2014.42
Nonhuman 4 145 21,738 802 2014.20
Nuclear magnetic resonance imaging 4 144 2,582 113
Nude mouse 4 145 5,420 149 2014.97
Rat 4 145 3,456 124 2014.43
Rats 4 143 2,374 91 2014.24
Tissue distribuition 4 145 3,387 114 2014.39
Treatment outcome 4 144 2,351 91 2014.37
Tumor growth 4 145 2,848 93 2014.22
Tumor volume 4 145 4,774 153 2014.52
Tumor xenograft 4 145 4,757 154 2014.24
Tumors 4 145 5,707 218 2014.76
Xenograft model antitumor assays 4 145 4,978 150 2014.41
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Acknowledgments

We acknowledge Camila Umbelino Carvalho e Fernando Vieira da Silva for helping us in programming language and performing graphs in software RSudio 1.1.383. This work was supported by São Paulo Research Foundation (FAPESP grants #2017/19504-0 and 2018/06003-5).

Footnotes

Author contributions

All three authors have made substantial contributions to the acquisition, analysis and interpretation of the data in this study. All authors also critically revised the manuscript. The authors agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Table S1.

List of keywords generated by VOSviewer

Id Cluster Links Total link strength Ocurrences Avg. pub. year
Antibiotics, antineoplasic 1 142 2,748 91 2014.32
Antineoplasic agent 1 145 15,216 544 2014.86
Antineoplastic agents 1 145 12,789 466 2014.52
Antineoplastic agents, phytogenic 1 144 3,049 110 2014.37
Breast cancer 1 145 25,473 1,133 2014.20
Cancer 1 145 2,299 111 2014.31
Cancer chemotherapy 1 145 3,622 135 2014.11
Cancer therapy 1 145 3,606 150 2014.02
Chemistry, pharmaceutical 1 140 2,597 89 2014.53
Chemotherapy 1 145 3,395 132 2014.67
Docetaxel 1 142 3,174 128 2014.39
Doxorubicin 1 145 10,337 395 2014.38
Drug carrier 1 145 12,086 427 2014.87
Drug carriers 1 145 13,199 478 2014.49
Drug delivery 1 145 5,533 226 2014.32
Drug delivery system 1 145 17,825 666 2014.43
Drug delivery systems 1 145 8,691 318 2014.51
Drug efficacy 1 145 8,873 299 2014.26
Drug formulation 1 145 6,652 237 2014.35
Drug resistance 1 145 2,946 93 2014.90
Drug resistance, neoplasm 1 145 3,199 110 2014.90
Drug safety 1 137 2,056 85 2014.24
Drug targeting 1 145 3,707 137 2014.07
Encapsulation 1 142 2,966 104 2014.22
Epidermal growth receptor 2 1 145 2,759 129 2014.37
Liposome 1 145 3,933 165 2014.10
Liposomes 1 144 2,916 114 2014.18
Macrogol 1 145 5,495 191 2014.18
Macrogol derivate 1 144 5,737 177 2015.06
Micelle 1 145 4,475 149 2014.53
Micelles 1 144 4,104 137 2014.53
Molecularly targeted therapy 1 145 2,453 86 2014.37
Multigrud resistance 1 144 2,708 93 2014.69
Nanocarrier 1 145 5,136 179 2014.50
Nanomedicine 1 145 4,366 179 2014.36
Nanotechnology 1 145 3,660 200 2014.15
Neoplasms 1 145 4,503 198 2014.15
Paclitaxel 1 145 6,411 277 2014.26
Polyethylene glycols 1 145 7,772 265 2014.51
Polymer 1 145 4,412 163 2014.44
Polymers 1 145 4,078 149 2014.62
Antineoplastic activity 2 145 12,103 411 2014.35
Biocompatibility 2 145 3,250 129 2014.44
Breast cancer cell line 2 144 6,465 231 2015.23
Cancer cell 2 145 6,297 267 2013.88
Cancer cell culture 2 143 3,361 150 2013.12
Cell strain MCF-7 2 141 1,972 90 2012.83
Cell survival 2 145 9,525 352 2014.43
Cell viability 2 145 7,251 267 2014.50
Chitosan 2 144 2,019 91 2014.87
Concentration response 2 145 2,310 86 2014.05
Confocal microscopy 2 144 2,658 99 2014.35
Cytotoxicity 2 145 10,253 406 2014.37
Drug conjugation 2 145 3,059 103 2014.53
Drug cytotoxicity 2 145 5,914 204 2014.47
Drug release 2 145 9,809 338 2014.57
Drug stability 2 145 3,688 135 2014.22
Drug synthesis 2 145 3,459 132 2014.37
Drug uptake 2 145 3,290 109 2014.45
Endocytosis 2 145 3,664 125 2014.46
Flow cytometry 2 145 4,128 158 2914.37
Fluorescence microscopy 2 145 2,217 89 2014.13
Human cell 2 145 20,170 787 2014.32
Hydrogen ion concentration 2 145 2,670 89 2014.37
IC50 2 143 3,263 103 2015.41
In vitro study 2 145 16,554 584 2014.39
Infrared spectroscopy 2 143 2,917 122 2014.70
Internalization 2 145 3,244 112 2014.53
Nanoencapsulation 2 145 5,072 175 2014.21
Particle size 2 145 14,569 551 2014.48
pH 2 145 4,373 154 2014.63
Physical chemistry 2 145 2,814 103 2014.48
Polyglactin 2 145 2,349 87 2014.11
Scanning electron microscopy 2 144 2,429 111 2014.59
Surface property 2 145 2,998 113 2014.47
Synthesis 2 145 3,766 138 2014.72
Transmission electron microscopy 2 145 5,382 227 2014.34
Unclassified drug 2 145 16,929 685 2014.13
Zeta potential 2 145 6,990 253 2014.44
Apoptosis 3 145 9,513 354 2014.65
Breast cancer cells 3 145 2,200 105 2014.30
Breast neoplasms 3 145 18,161 729 2014.37
Breast tumor 3 145 4,316 182 2014.31
Cell culture 3 145 3,973 169 2014.63
Cell death 3 145 5,057 193 2014.63
Cell line, tumor 3 145 21,152 814 2014.33
Cell proliferation 3 145 6,910 263 2014.48
Cells 3 145 5,212 226 2914.90
Chemistry 3 145 22,331 855 2015.02
Cytology 3 145 4,356 187 2015.14
Diseases 3 145 9,406 400 2014.87
Dose response 3 145 2,356 87 2014.91
Drug effects 3 145 15,154 527 2015.11
Gene expression 3 142 2,240 96 2014.54
Genetics 3 145 4,557 178 2014.98
Gold 3 143 3,108 161 2014.73
Gold nanoparticle 3 144 2,840 148 2014.28
Human 3 145 33,652 1,481 2014.47
Humans 3 145 31,754 1,340 2014.39
MCF-7 cell line 3 145 8,507 308 2014.82
MCF-7 cell lines 3 143 4,219 165 2016.04
MCF-7 cells 3 145 10,907 419 2014.75
Metabolism 3 145 13,700 530 2014.99
Metal nanoparticle 3 144 2,822 146 2014.90
Metal nanoparticles 3 143 3,623 191 2014.61
Nanoparticle 3 145 20,739 856 2014.54
Nanoparticles 3 145 21,557 918 2014.55
Pathology 3 145 12,505 474 2014.92
Procedures 3 145 9,188 368 2015.16
Protein expression 3 145 5,090 200 2014.33
RNA, small interfering 3 143 2,303 86 2014.43
Small interfering RNA 3 145 2,952 120 2014.33
Tumor cell line 3 145 16,200 584 2014.95
Ultrastructure 3 144 3,356 129 2015.16
Animal 4 145 16,923 563 2014.90
Animal cell 4 145 7,522 262 2014.27
Animal experimente 4 145 17,049 571 2014.31
Animal model 4 145 15,890 524 2014.33
Animal tissue 4 145 8,724 293 2014.27
Animals 4 145 22,161 793 2014.29
Bagg albino mouse 4 145 6,713 193 2015.00
Cancer inhibition 4 145 7,263 231 2014.35
Drug distribuition 4 145 5,077 157 2014.28
Drug screening 4 145 5,716 180 2014.83
Female 4 145 25,711 1,023 2014.41
In vivo study 4 145 11,108 360 2014.31
Magnetic resonance imaging 4 142 2,176 87
Magnetite nanoparticle 4 144 2,027 90 2014.50
Magnetite nanoparticles 4 142 2,119 95 2014.35
Male 4 145 4,262 151 2014.26
Mice 4 145 14,860 517 2014.18
Mice, inbred balb c 4 145 8,385 256 2014.44
Mice, nude 4 145 6,470 194 2014.43
Mouse 4 145 19,679 679 2014.42
Nonhuman 4 145 21,738 802 2014.20
Nuclear magnetic resonance imaging 4 144 2,582 113
Nude mouse 4 145 5,420 149 2014.97
Rat 4 145 3,456 124 2014.43
Rats 4 143 2,374 91 2014.24
Tissue distribuition 4 145 3,387 114 2014.39
Treatment outcome 4 144 2,351 91 2014.37
Tumor growth 4 145 2,848 93 2014.22
Tumor volume 4 145 4,774 153 2014.52
Tumor xenograft 4 145 4,757 154 2014.24
Tumors 4 145 5,707 218 2014.76
Xenograft model antitumor assays 4 145 4,978 150 2014.41
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Articles from International Journal of Nanomedicine are provided here courtesy of Dove Press

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