Table 2.
A brief summary of the application of nano-based DDS in selected cancers.
| Studying Group [Ref.] | NPs Description |
Targeting Mechanism | Target | Drug(s) | Cancer Model | Results of Findings |
|---|---|---|---|---|---|---|
| Kim et al. (2016) [96] | Exosome | Specific endocytosis and/or fusion with plasma membranes |
No data | PTX | 3LL-M27 cells; MDCKWT and resistant MDCKMDR1 cancer cells; pulmonary metastases in Lewis lung carcinoma (LLC) mouse model |
The incorporation of PTX into exosomes significantly increased drug accumulation levels in both sensitive and resistant cancer cells; a significant (p < 0.05) inhibition of metastases growth by exoPTX treatment was demonstrated |
| Iannazzo et al. (2017) [97] | QDs | Active targeting |
Biotin receptors | DOX | A549 cells | Improved delivery of conventional chemotherapeutics by using QDs as nanocarrier |
| Zhao et al. (2017) [98] | Micelles | Passive targeting |
EPR | PTX and DOX |
A549 cells | A fixed and high drug loading content of 24.2% (PTX~14.8% and DOX~9.4%) with a precise ratio of PTX and DOX to realize the synchronized and controlled release |
| Xie et al. (2019) [99] | PMs | Not mentioned |
No data | PTX and ligustrazine |
A549 cell lines; xenograft tumor mice model |
Strong inhibition on tumor metastasis; enhance the accumulation of drugs at tumor sites; tumor volume ratios were 26.47% ± 8.23 for blank control, 21.43% ± 9.45 for free PTX, 14.65% ± 8.13 for dequalinium (DQA) modified PTX plus ligustrazine micelles, respectively |
| Zou et al. (2019) [100] | SeNPs | Specific endocytosis |
CD44 receptor | PTX | A549 cell lines; A549 tumor-bearing mice |
Greater uptake of PTX in A549 cells; negligible toxicity; PTX and HA-Se@PTX at 4 μg/mL PTX dose dramatically inhibited the proliferation of A549 cells and the cell viability rates were 64.8, and 34.5%, respectively |
| Wu et al. (2019) [101] | Dendrimers | Coating with targeting cancer cell membrane proteins |
No data | DOX and icotinib | H1975, HCC827, and B16 cell lines; H1975 tumor-bearing mice |
High stability; superior targeting ability; minimal side effects; at the physiological pH 7.4, only 30.1% of the DOX and 27.3% of icotinib were released from the dendrimers within 48 h; the H1975 cell membrane-coated dendrimers resulted in 87.56% tumor inhibition, with the tumor weight 8.75-fold less compared to that of the PBS control group |
| Huang et al. (2019) [102] | PMs | Active targeting |
CD133 and CD44 receptor | Gefitinib | H446 and A549 cell lines; xenograft tumor mice model | The drug loading of the nanomicelles in each group was 7–9% and the encapsulation efficiency was ~80%; exhibited greater therapeutic efficacy against lung cancer-initiating cells than single-target |
| Zhang et al. (2019) [103] | Polymeric NPs | Specific endocytosis |
Epidermal growth factor receptor (EGFR) | Homoharringtonine (HHT) | BEAS-2B, A549, and NCI-H226 cell lines; A549 tumor bearing mice | Better therapeutic efficacy and fewer side effects; targeted recognition and stimuli response; the IC50 of the nanomedicine is 5.1 nM, while the IC50 of free HHT reaches up to 23.2 nM, a 4.5-fold increase |
| He et al. (2020) [104] | PMs | Not mentioned |
No data | PTX | A549 cells; A549 tumor bearing mice | Enhanced the retention of drugs in the tumor; sustained drug release property; the IC50 values of the PTX micelles at 24 h with no ambroxol (Ax) or combined with 100 μM Ax were 87.09 ± 4.12 ng/mL and 1.14 ± 0.08 ng/mL, respectively |
| Liang et al. (2020) [105] | NLCs | Specific endocytosis |
Glucose | PTX and GEM | LTEP-a-2, L929, and A549 cell lines; A549 tumor bearing mice | Targeted intracellular sequential drug release; the tumor volume in dual-drugs-loaded NLCs group was 2.6-fold smaller than those treated with the free drug combination |
| Zhang et al. (2015) [106] | Nanocrystals | Not mentioned |
No data | PTX | MDA-MB-231/Luc cells; MDA-MB-231/Luc tumor bearing mice | PEGylated PTX nanocrystals significantly enhanced the antitumor effect in treating in situ tumor or metastatic tumor bearing mice after intravenous administration |
| Guven et al. (2017) [107] | CNTs | Passive targeting |
EPR | Cisplatin | MCF-7 and MDA-MB-231 tumor bearing mice | A prolonged circulation time compared to free cisplatin which EPR effects resulting in significantly more cisplatin accumulation in tumors |
| Li et al. (2017) [108] | PLNs | Active targeting |
Human epidermal growth factor receptor-2 (HER-2) | Salinomycin | BT-474 ALDH+ and ALDH- cell; MDA-MB-361 ALDH+ and ALDH- cells; BT-474 tumor bearing mice |
Achieved the best therapeutic efficacy, resulting in a 79% decrease in tumor volume, whereas salinomycin obtained only moderate therapeutic efficacy (43% decrease) |
| Le et al. (2017) [109] | Viral NPs | Not mentioned |
No data | DOX | MDA-MB-231 cells; MDA-MB-231 tumor bearing mice | DOX-loaded viral NPs demonstrated efficacy in MDA-MB-231 cell although at lower efficacy than free DOX |
| Jiang et al. (2018) [110] | SiNPs | Not mentioned |
No data | DOX | EMT-6 and MCF -7 cell lines; EMT-6 tumor bearing mice | The tumor size and weight of DOX loaded SiNPs group was 2-fold and 1.7-fold smaller than that of free DOX group, and 4-fold and 2-fold smaller than that of PBS group |
| Zheng et al. (2019) [111] | SLNs | pH sensitivity |
No data | DOX | MCF cells lines; MCF/ADR DOX-resistant cells; MCF/ADR tumor bearing mice |
RGD-DOX-SLNs showed 5.58 fold higher area under the plasma concentration-time curve (AUC) compared with DOX solution; terminal half life (T1/2) and peak concentration (Cmax) of RGD-DOXSLNs was 10.85 h and 39.12 ± 2.71 L/kg/h |
| Fang et al. (2019) [112] | Polymeric NPs | Active targeting |
CD44 receptor | DTX | 4T1-Luc cells lines; 4T1-Luc tumor bearing mice | Drug loading efficiency (76.3−80.4%); steady in a nonreducing environment while was destabilized under 10 mM glutathione releasing ~90% of the DTX within 24 h; selective cellular uptake |
| Li et al. (2019) [113] | Liposome | Passive targeting |
EPR | Poria cocos extract and DOX | MCF cells lines; MCF/ADR DOX-resistant cells; MCF/ADR tumor bearing mice |
Higher safety; sensitized DOX to kill cells in drug-resistant tumors; the release rates of poria cocos extract from the liposome were > 70% within 6–8 h, while DOX was released completely after 12 h |
| Lei et al. (2019) [114] | MOFs | Passive targeting |
EPR | DOX | 4T1, MDA-MB-231, MCF-7, and ZR-75-30 cell lines; 4T1 tumor bearing mice | Good safety profile; highly effective antitumor ability |
| Dancy et al. (2020) [115] | Polymeric NPs | Active targeting |
Fibroblast growth factor–inducible 14 (Fn14) receptor | PTX | 231-Luc cell lines; 231-Luc tumor-bearing mice; 231-Br-Luc tumor-bearing mice |
Tumor cell–specific uptake; long blood circulation time; excellent tumor tissue penetration; the average tumor doubling time in the NPs treated mice was 32 days compared to 17 and 20 days for saline- or Abraxane-treated mice, respectively |
| Han et al. (2020) [116] | Liposomes | Specific endocytosis |
ERs | PTX | MCF-7 cell lines; MCF-7 tumor bearing mice |
Encapsulation efficiency of 88.07 ± 1.25%; prolonged half-life of the drug; the elimination half-lives of PTX and PTX liposomes were 1.79 and 20.98 h, respectively |
| Zafar et al. (2020) [117] | LNCs | Passive targeting |
EPR | DTX and THQ | MCF-7 and MDA-MB-231 cell lines; Ehrlich ascites carcinoma bearing mice |
Encapsulation efficiency of DTX and THQ were found to be 86.79 ± 3.79% and 95.17 ± 1.61%, respectively; controlled drug release; re-sensitized cancer cells to DTX; a 2.85-folds decrease in tumor volume was observed with LNCs treated group compared to control group |
| Xu et al. (2020) [118] | PMs | Active targeting |
Sialic acid residues | DOX | MCF-7/ADR cell lines; MCF-7/ADR tumor bearing mice | MDR reversal; good stability in neutral environment; ~50% MCF-7/ADR cells were killed with DOX micelles treated compared to ~15% cells death induced by free DOX |
| Guo et al. (2020) [91] | RNA NPs | Active targeting |
EGFR | PTX | MDA-MB-231 cell lines; MDA-MB-231 tumor bearing mice | Undetectable toxicity or immune stimulation; the in vitro cell apoptosis assay revealed that 45.1% of the cells underwent apoptosis after 24 h treatment with RNA NPs, in comparison to free PTX (24.6%) |
| Teijeiro-Valiño et al. (2018) [119] | Polymeric NPs | Active targeting |
CD44 receptor | DTX | A549 lung cancer cells; orthotopic lung cancer model; PC patient derived xenograft model | Dual targeting properties (to the tumor and to the lymphatics); a dramatic accumulation of DTX in the tumor (37-fold the one achieved with Taxotere®) |
| Lin et al. (2019) [120] | Liposome | Specific endocytosis |
EGFR | GEM and HIF1α-siRNA | PANC-1 cell lines; PANC-1 tumor bearing mice | Increased targeting specificity of liposome carrier; increased the total amount of apoptosis cells; GE-GML/siRNA showed 4-fold reduction in tumor compared to control group |
| Madamsetty et al. (2019) [121] | NDs | Passive targeting |
EPR | DOX | BxPC3, 6741 and PANC-1 cell lines; orthotopic PDAC xenograft model | A considerable improvement over free drug; no abnormalities of major organs; NDs alone showed no cytotoxicity at doses up to 25 μg/mL, irrespective of whether the cells were grown in the absence or presence of FBS |
| Massey et al. (2019) [122] | Polymeric NPs | Not mentioned |
No data | PTX | AsPC1, PANC-1, MIA PaCa-2, and HPAF-II cell lines | NPs administration (10 mg/kg) significantly (P << 0.05) inhibited tumor growth, even in pre-exposed mice as determined by significant (P << 0.05) inhibition of bioluminescence counts ideal properties for nano-scale drug delivery; |
| Madamsetty et al. (2019) [123] | NDs | Passive targeting |
EPR | Irinotecan and curcumin | AsPC-1 and PANC-1 cells; orthotopic PDAC xenograft model | Exerted immunomodulatory effects; dual payload |
| Sun et al. (2020) [124] | PMs | Passive targeting |
EPR | NLG919 and PTX | PANC02 and H7 cell lines; PANC02 tumor bearing mice; 4T1 BC model | Improved tumor inhibition effect; more immunoactive tumor microenvironment; micelles showed a more favorable release kinetics of PTX, and only 35% of PTX was slowly released within 72 h |
| Etman et al. (2020) [125] | Polymeric NPs | Specific endocytosis |
Lactoferrin (Lf) and CD44 receptors | Quinacrine (QC) | PANC-1 cell lines; orthotopic PC model | pH triggered release; the loading efficiency of the dual coated formulation was 19.5 ± 1.9% compared to 23.6 ± 2.4% for uncoated formulation. |
| Elechalawar et al. (2020) [126] | Au NPs | Active targeting |
EGFR | GEM | PANC-1, AsPC-1, CAF-19, and HPDE cell lines | Enhanced cellular uptake and cytotoxicity to pancreatic cancer cells (PCCs) |
| Han et al. (2020) [127] | MNPs | Active targeting |
No data | GEM | PANC-1 and HUVEC cell lines; PANC-1 tumor bearing mice | Targeted delivery and effective accumulation; the GEM-loaded MNPs exhibited higher cytotoxicity at pH 6.5 than that at pH 7.4, which might be attributed to pH-dependent enhanced cellular uptake |
| Zhai et al. (2018) [128] | APO | Specific endocytosis |
Transferrin receptor 1 (TfR1) and heparan sulfate proteoglycan | Vincristine sulfate (VCR) | bEnd.3, HUVEC, and U87MG cell lines; U87MG tumor bearing mice | Higher glioma localization; the VCR encapsulation efficiency was approximately 39.8 ± 0.9%; treatment with this NPs significantly prolonged the median survival time (35 days), which was 1.8 and 1.6-fold higher than that of physiological saline and free VCR, respectively |
| Guo et al. (2018) [129] | PMs | Specific endocytosis |
IL-13R | CMS | BT325 cell lines; Luc-BT325 tumor bearing mice | BBB penetration; targeting glioma cells; the apoptosis rate of BT325 cells induced by the PMs nearly 80% |
| Zou et al. (2018) [130] | Polymeric NPs | Specific endocytosis |
Lipoprotein receptor related protein receptor | DOX and lexiscan (Lex) | U87MG tumor bearing mice | Improved blood circulation time; BBB penetration; the biodistribution of nanomedicines demonstrated that orthotopic brain tumor accumulation was 21.9 fold higher than that of free DOX controls |
| Meng et al. (2019) [131] | PMs | Not mentioned |
No data | DOX | HBMEC and C6 cell lines; GBM-bearing mice model | The drug encapsulation efficiency and loading capacity in DOX BO-PMs were (95.69 ± 0.49)% and (14.62 ± 0.39)%, respectively; enhanced the transport efficiency of DOX across the BBB; exhibited a quick accumulation in the brain tissues |
| Wang et al. (2019) [132] | Nanoemulsion | Active targeting |
CD44 and nucleolin | Shikonin (SKN) and DTX | U87 cell lines; orthotopic luciferase-transfected-U87 bearing nude mice | BBB penetration; overwhelming inhibition of the orthotopic luciferase-transfected-U87 glioma-bearing nude mice; after incubating cells for 8 h, the nanoemulsion induced apoptosis in 71.3 ± 4.2% of U87 cells |
| Younis et al. (2019) [133] | Polymeric NPs | Not mentioned |
No data | Iguratimod (IGU) | U87, U118, and U251 cell lines; xenograft tumor mice model | Without any visible organ toxicity; significant inhibition of tumor growth; cross BBB |
| Caban-Toktas et al. (2020) [134] | Polymeric NPs | Not mentioned |
No data | R-flurbiprofen and PTX | RG2 cell lines; Rat RG2 glioma tumor model | Reduced inflammation in the peri-tumoral area; enhanced anti-tumoral activity against glioma |
| Zhang et al. (2018) [135] | Polymeric NPs | Specific endocytosis |
Asialoglycoprotein receptors (ASGP-R) | Triptolide (TP) | SMMC7721 and A549 cells; HCC xenograft mouse model; orthotopic HCC mice model | Sustained release; targeted delivery; high liver tumor accumulation in vivo |
| Yao et al. (2019) [136] | Liposome | Not mentioned |
No data | Sorafenib (Sf) and VEGF-siRNA | HepG2 cells; H22 tumor-bearing mice | Improved anti-tumor efficiency |
| Han et al. (2019) [137] | Polymeric NPs | Not mentioned |
No data | Polymeric SN38 prodrugs (pSN38) and apatinib (Apa) | Huh-7, LM3, and HepG2 cell lines; HCC xenograft mouse model |
Reduced drug resistance; the sequential release of both encapsulated drugs |
| Zhang et al. (2019) [138] | MSNs | Specific endocytosis | CD44 receptor | DOX and berberine (BER) | HepG2, H22, HL-7702, HCC cells, and NIH-3T3 cell lines; H22 tumor-bearing mice | Efficient tumor-inhibiting effects; decreased regrowth activity; the apoptotic rates of DOX+BER and DOX+BER loaded MSNs were 34.93 and 48.10%, respectively |
| Xu et al. (2019) [139] | Oxide NPs | Specific endocytosis | CD44 receptor | DOX and Cu (DDC)2 | MCF-7 and HepG2 cell lines; mouse models of ectopic hepatocellular carcinoma | Improved stability; specific targeting of HCC; good synergistic effect; the tumor volume and tumor weight of the oxide NPs treated group reduced to 60.32% and 60.39% compared to the control group, respectively |
| Tang et al. (2020) [140] | Liposomes | Active targeting |
Folate receptor (FR) | DOX | 4T1 cell lines; H22 and Eca9706 tumor-bearing mice | High drug load capacity; effectively taken up by cancer cells; no obvious toxicity |
| Hefnawy et al. (2020) [141] | Polymeric NPs | Active targeting |
ASGP-R | DOX | Hep-G2 cell lines; HCC-bearing rats |
Improved intracellular drug delivery and uptake; enhanced safety profile; the ability of the NPs system to enhance the intracellular uptake of the drug by 4-fold and 8-fold after 4 h and 24 h of incubation, respectively |