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. 2020 Jun 29;27(1):909–916. doi: 10.1080/10717544.2020.1778815

Functionalized MoS2-nanoparticles for transdermal drug delivery of atenolol

Kai Zhang a, Yanling Zhuang b, Weidan Zhang a, Yali Guo c, Xiaochang Liu d,e,✉
PMCID: PMC8216476  PMID: 32597334

Abstract

Molybdenum disulfide (MoS2) has excellent photothermal conversion abilities, an ultra-high specific surface area, and has been extensively explored for use in biomedicine. However, the high toxicity associated with MoS2 has limited its biological applications for in vivo photothermal therapy and drug delivery systems. Herein, we have developed cationic hydroxyethyl cellulose (JR400) surface-modified MoS2 nanoparticles (NPs) that are responsive to near-infrared (NIR) laser irradiation as a transdermal drug delivery system (TDDS). Herein, we confirmed the preparation of hexagonal phase MoS2 with robust surface modification with JR400. The flower-like morphology of the NPs had an average diameter of 355 ± 69.3 nm limiting the absorption of the NPs through the stratum corneum. With the ability to efficiently load 90.4 ± 0.3% of the model drug atenolol (ATE), where 1 g of JR400-MoS2 NPs was able to load 3.6 g ATE, we assayed the controlled release capacity in vitro skin penetration studies. These JR400-MoS2 NPs showed further enhancement under NIR stimulation, with a 2.3-fold increase in ATE skin penetration. Furthermore, we verified in vivo that these JR400-MoS2 NPs do not cause skin irritation suggesting that they are promising new TDDS candidates for small molecule drugs.

Keywords: Molybdenum disulfide, transition-metal dichalcogenides, cationic hydroxyethyl cellulose, transdermal drugs, drug release, biomedicine

1. Introduction

Molybdenum disulfide (MoS2) is a typical transition-metal dichalcogenide with a layered structure consisting of individual S-Mo-S layers weakly bound by Van der Waals forces (Chen et al., 2015; Dhall et al., 2015; Wang et al., 2019). The remarkable physicochemical properties of MoS2 has led to extensive research and applications in a wide variety of fields, including photochemistry, optoelectronics, catalysis, hydrogen storage, and biomedicine (Zhu et al., 2013; Qiao et al., 2016; Zhang et al., 2016). MoS2 has been widely investigated for applications in drug delivery systems because of its ultra-high specific surface area (Liu et al., 2014; Yin et al., 2014; Wang et al., 2015; Wu et al., 2018; Zhang et al., 2018). Liu et al. used MoS2 nanosheets paired with a PEG carrier to load a variety of therapeutic molecules, where the drug loading ratio of the MoS2 nanosheets was superior to graphene oxide (Liu et al., 2014). Additionally, the release of the loaded drug molecules from the MoS2 is inducible using 808-nm near-infrared (NIR) laser irradiation (Yin et al., 2014). The excellent photothermal performance of MoS2 has inspired further use in photothermal therapies (Wang et al., 2015; Liu et al., 2016; Huang et al., 2017; Zhang et al., 2017; Fu et al., 2018). Wang et al. evaluated a MoS2/Bi2S3 composite as a photothermal therapy agent (Wang et al., 2015). Chou et al. developed MoS2-based NIR photothermal agents comprising Ce-MoS2 nanosheets that offered higher photothermal performance than graphene and gold nanorods (GNRs) (Chou et al., 2013). However, the toxicity of MoS2 has presented challenges for its use in photothermal therapy and drug delivery in vivo. Yu et al. found that 20 mg/L chitosan-functionalized MoS2 micro-sheets exhibited cytotoxicity in the gills and liver of adult zebrafish (Yu et al., 2018). Furthermore, nano-MoS2 and MoS2 nanosheets exfoliated with t-Bu-Li and n-Bu-Li have been found to be cytotoxic (Chng et al., 2014; Wu et al., 2019). To date, the in vivo toxicity of MoS2 remains a critical barrier for its use in biomedical applications.

Toxicity of MoS2 can be mitigated by developing biomedical applications that can be used ex vivo. Transdermal drug delivery systems (TDDSs) are an innovative approach to delivering drugs into the blood at a controlled rate via the skin. TDDSs avoid the first-pass effect and improve patient compliance because they are applied topically (Labouta et al., 2011; Anselmo & Mitragotri, 2014; Pastore et al., 2015; Liu et al., 2017a, 2017b; Charoensumran & Ajiro, 2020). Materials larger than 45 nm are stopped at the stratum corneum (SC) of untreated intact human skin, allowing for sustained and controlled drug release (Labouta et al., 2011). MoS2 is expected to be an outstanding TDDS material, but, to the best of our knowledge, has yet to be reported in the literature.

Herein, we aimed to overcome the toxicity of MoS2 in biomedical applications by developing an innovative TDDS using three-dimensional (3D) flower-like MoS2 nanoparticles (NPs) produced via a simple hydrothermal approach (Zhang et al., 2015). Cationic hydroxyethyl cellulose (JR400) was electrostatically bound to the negatively charged surface of the MoS2 NPs, increasing its colloidal stability and biocompatibility (Liu et al., 2006; Ran et al., 2019). The MoS2 NPs coated with JR400 (JR400-MoS2 NPs) were further characterized using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). We chose to load the J400-MoS2 NPs with the model drug atenolol (ATE), a β1-adrenergic receptor blocking agent prescribed for hypertension. The drug load efficacy and photothermal conversion effect were evaluated, and the controlled release capacity of JR400-MoS2 NPs was demonstrated in in vitro drug release and skin penetration assays.

2. Materials and methods

2.1. Materials

Ammonium molybdate tetrahydrate and thiourea were obtained from Shanghai Macklin Biochemical Co. Ltd. (Shanghai, PR China). Cationic hydroxyethyl cellulose (JR400, Mw = 8,000,000 g/mol) was purchased from Shandong Usolf Chemical Technology Co. Ltd. (Linyi, PR China). Atenolol (HPLC grade, 98%) was purchased from Rhawn Chemical Technology Co. Ltd. (Shanghai, PR China). HPLC grade methanol and phosphoric acid were used throughout. All other chemicals were reagent grade and obtained commercially. All chemicals were used as received without any further purification. Ultrapure water was purified by a Milli-Q system (18.2 MΩ).

2.2. Synthesis of JR400-MoS2 NPs

A facile and straightforward hydrothermal method was used to synthesize flower-like MoS2 NPs (Zhang et al., 2015). In detail, 1.24 g of ammonium molybdate tetrahydrate and 2.28 g of thiourea were dissolved in 36 mL of ultrapure water under vigorous stirring for 30 min to form a homogeneous solution. The mixture was transferred into a 50-mL Teflon-lined stainless-steel autoclave and heated at 220 °C for 6 h. After unassisted cooling to room temperature, the products were collected by centrifugation and washed with ultrapure water and absolute ethanol several times, then dried in a vacuum at 60 °C.

Afterward, 1.0 g of the obtained flower-like MoS2 NPs was stirred into 200 mL of aqueous containing 0.2 g of JR400. The suspension was ultrasonicated for 1 h, then heated at 80 °C for 4 h. The product was separated by centrifugation and then washed with deionized water and absolute ethanol several times. After vacuum drying at 60 °C for 24 h, we obtained the JR400-MoS2 NPs (black powder).

2.3. Characterization of JR400-MoS2 NPs

Spectrum of JR400-MoS2 NPs was collected using the KBr pellets method with ATR-FTIR spectroscopy (Perkin Elmer 2000, ‎Waltham, MA). The crystalline structure of JR400-MoS2 NPs was studied using Rigaku SmartLab X-Ray Diffraction with Cu Kα radiation. The microstructure of the samples was investigated using TEM (JEOL-2100F, Akishima, Japan), which was operated at 200 kV. The particle size and zeta potential were measured using dynamic light scattering (DLS, Melvin 2000). The colloidal stability was analyzed by zeta potential and sedimentation volume ratio. The sedimentation volume ratio was determined by the ratio of the height after (Hu) and before (H0) the sedimentation.

2.4. Photothermal conversion performance

JR400-MoS2 NPs were suspended in water at varying concentrations from 0.1 to 1.0 mg/mL for irradiation with an 808-nm laser (0.5 W/cm2) to measure the photothermal effects. The laser power density was also varied between 0.2 and 1.0 W/cm2. The thermal stability of the JR400-MoS2 NPs at 0.5 mg/mL was determined by NIR-stimulation (0.5 W/cm2) for 5 min over three on-off cycles. The temperature of the solution was measured by a magnetic stirrer equipped with a temperature probe.

2.5. Drug loading

ATE was loaded onto the surface of JR400-MoS2 NPs by mixing different concentrations of the drug with 0.5 mg/mL JR400-MoS2 NPs in 5 mL of phosphate-buffered saline (PBS) (pH = 7.0). The mixture was stirred for 2 h and incubated at 32 °C for 24 h. The free drug was removed by centrifugation at 5000 r/min for 10 min, and the JR400-MoS2-ATE NPs were washed with ultrapure water three times. The JR400-MoS2-ATE NPs were dried at 60 °C for 24 h under vacuum and stored at room temperature. The drug loading was calculated by the concentration of free drug in the supernatant, as analyzed by HPLC. Drug loading efficiency and drug loading percent were calculated using the following equations:

Drug loading efficiency=the amount of loading drugthe amount of NPs ×100%
Drug loading percent=the amount of loading drugthe amount of total drug×100%

2.6. In vitro drug release and skin permeation experiments

2.6.1. Preparation of the donor solution

A donor solution was prepared by adding 25 mg JR400-MoS2-ATE into 50 mL PBS. In order to form a uniform suspension, the mixture was stirred for 1 h, followed by sonication for 15 min. The suspension was added into the donor chamber of a two-chamber diffusion cell immediately after preparation.

2.6.2. In vitro drug release experiments

Drug release was assayed using a two-chamber diffusion cell separated by a 0.22-μm cellulose microporous membrane. 4.0 mL of JR400-MoS2-ATE solution was added into the donor chamber, and an equal volume of PBS (pH 7.4) containing 15% PEG400 (PBS-PEG400) was added into the receptor chamber. Both chambers were continuously stirred with a magnetic stirrer at 600 rpm and kept at 32 °C. 2.0 mL from receptor chamber was collected at 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 28, 32, 36, and 48 h, and then replaced with the same volume of fresh PBS-PEG400. The donor solution was irradiated with laser (0.5 W/cm2) for 5 min after sampling.

2.6.3. In vitro skin permeation experiments

Male Wistar rats (180–220 g, 6–8 weeks old) were supplied by Liaoning Changsheng (Liaoning, China). Full-thickness skin was prepared as follows: (1) the rat was anesthetized with urethane (20% w/v, 6 mL/kg, i.p.), and the abdominal hair was shaved off. (2) Abdominal skin was excised after the rat was sacrificed. (3) The adhering subcutaneous tissues were carefully removed. All the procedures were performed in accordance with the NIH Guidelines for the Care and Use of Laboratory Animals and were approved by the Animal Ethics Committee of Shenyang Medical College.

The two-chamber diffusion cell was used for the permeation experiments. The skin was mounted between the two chambers with SC facing the donor solution and epidermis facing the receptor solution. Sample collection and drug concentration measurements were performed in the same manner as drug release study, except that sample collection was conducted at 2, 4, 6, 8, 12, 24, 28, 32, 36, and 48 h with NIR-stimulation after every sampling. The cumulative drug skin penetration amount was calculated using the drug concentration in the receptor solution, taking the effect of sampling into account.

2.6.4. HPLC analysis of the drug

The drug concentration was determined by Hitachi HPLC (Tokyo, Japan), which consisted of a Pump L-2130, AutoSampler L-2200, UV-detector L-2420, and C18 reversed-phase column (200 × 4.6 mm, 5 μm, ODS-2 Waters, Milford, MA). The mobile phase for the ATE was a mixture of methanol, water, and phosphoric acid solution (70:30:0.1, v/v). The column temperature was 25 °C, the flow rate was set at 0.7 mL/min, and the free drug was detected at a wavelength of 275 nm.

2.7. In vivo skin erythema study

A Mexameter® (MX 16, Courage & Khazaka Co., Cologne, Germany) was used to measure the biocompatibility of JR400-MoS2 NPs by measuring the erythema index (EI) of the skin. Rabbits were used to assess potential skin irritation caused by JR400-MoS2 NPs compared with a 10% (w/v) aqueous solution of sodium dodecyl sulfate (SDS) as the positive control. The dorsal skin of the rabbits was shaved and divided into three separate sections, each with an area of 2.5 cm × 2.5 cm. The initial EI values of the chosen sections were measured as a baseline value (EI0) before topical application of 500 μL of PBS, JR400-MoS2 NPs, or 10% SDS in their respective sections. The application sites were covered with double-layer gauze in order to prevent perturbation. After 8 h, the excess solutions were removed, and the predefined sections were gently cleaned with cotton wool swabs. The EIt was measured at set intervals and ΔEI was calculated by subtracting EI0 from EIt. This experiment was performed in quadruplicate.

2.8. Statistical analysis

Results are reported as the mean ± SD. The data were subjected to analysis of variance (ANOVA) using the SPSS 16.0 software (SPSS Inc., Chicago, IL). Significance levels are reported for p< .05.

3. Results and discussion

3.1. Synthesis and characterization of JR400-MoS2 NPs

Flower-like MoS2 NPs were synthesized using a previously reported hydrothermal process using ammonium molybdate tetrahydrate and thiourea precursors to produce polyacrylamide (PAM) modified MoS2 NPs (Wang et al., 2019). NPs were subsequently surface modified with JR400 (Figure 1), a water-soluble cellulose derivative that is currently used in skincare products (Li et al., 2012).

Figure 1.

Figure 1.

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Schematic showing the assembly of JR400-MoS2 NPs and their application for the controlled release of ATE via transdermal administration.

The JR400 surface modification was evaluated using ATR-FTIR spectroscopic analysis (Figure 2). The peaks present at 2875 cm–1, 2974 cm–1, and 3409 cm–1 were attributed to the symmetrical stretching vibrations of the C–H bond, asymmetrical stretching vibrations of the C–H bond, and stretching vibration of the O–H band from the JR400 molecule, respectively, indicating that the MoS2 NPs were readily surface-modified with JR400.

Figure 2.

Figure 2.

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ATR-FTIR spectra of JR400-MoS2 NPs.

The XRD patterns exhibited five well-resolved diffraction peaks at 2θ = 14.4°, 32.7°, 39.5°, 49.8°, and 58.3°, which can be assigned to the (002), (100), (103), (105), and (110) diffraction planes, respectively (Figure 3). These planes correspond to the hexagonal phase of MoS2 (JCPDS no. 37-1492) (Tang et al., 2013). No other diffraction peaks were observed; thus, a hexagonal phase of MoS2 was prepared.

Figure 3.

Figure 3.

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The XRD pattern of the JR400-MoS2 NPs corresponding with the hexagonal phase of MoS2.

The grain size, morphology, and structure of the JR400-MoS2 NPs were investigated using scanning electron microscopy (SEM), TEM, and high-resolution TEM (HRTEM) (Figure 4). The SEM images indicated that the JR400-MoS2 NPs formed via irregular curling and winding of the thin MoS2 nanosheets (Figure 4(a)). The structure was studied in more detail using TEM and HRTEM. TEM revealed the NPs had a flower-like morphology (Figure 4(b)), consistent with the SEM images. HRTEM showed that the NPs were made from overlapping MoS2 nanosheets, matching previous reports in the literature (Tang et al., 2012). The lattice spacing of the MoS2 (002) plane was observed in the enlarged HRTEM image (Figure 4(c)), where the 0.63-nm lattice spacing was consistent with the XRD results.

Figure 4.

Figure 4.

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(a) SEM, (b) TEM, and (c) HRTEM images were used to visualize the grain size, morphology, and structure of the JR400-MoS2 NPs.

The JR400-MoS2 NPs had an average diameter of 355 ± 69.3 nm (PDI = 0.259), as obtained by DLS, similar to the size obtained by HRTEM image (Figure 4(c)). Generally, particles larger than 45 nm are stopped by the SC of skin (Labouta et al., 2011). Thus, the potential in vivo toxicity of JR400-MoS2 NPs is significantly reduced as it cannot translocate into the bloodstream. Furthermore, the JR400-MoS2 NPs could be used in TDDS for the controlled release of the drug across the SC.

The colloidal stability of JR400-MoS2 NPs and MoS2 NPs was explored using zeta potential, sedimentation volume ratio, and dispersion times. The zeta potential of the MoS2 NPs was measured to be –14.64 ± 1.72 mV, while the zeta potential of JR400 MoS2 NPs was found to be significantly more negative at –25.52 ± 2.15 mV, indicating that the JR400 functionalization increases the stability of the particle (Khafaji et al., 2019). After five days of sedimentation, the Hu/H0 of JR400-MoS2 NPs and MoS2 NPs were 0.95 ± 0.03 and 0.22 ± 0.12, respectively (Figure 5). The results were probably related to hydroxyl groups in JR400, which could form hydrogen bond with water. Overall, modifying the surface of the MoS2 NPs with JR400 made them more stable in water.

Figure 5.

Figure 5.

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The colloidal stability of JR400-MoS2 NPs: sedimentation volume ratio (Hu/H0) versus time.

3.2. Photothermal conversion performance study

The photothermal properties of NP drug carriers have been reported to have a substantial effect on drug release (Yin et al., 2014). Previous studies have shown MoS2 exhibits absorption at 808 nm (Yang et al., 2018). The conversion efficiency of the JR400-MoS2 NPs was studied by changing the power density of the laser and concentration of the MoS2 NPs. The temperature of the 1.0 mg/mL JR400-MoS2 NP solutions increased rapidly to 86.6 °C during the 5 min of irradiation, while the control samples exhibited minimal changes under the same conditions (Figure 6(a)). The temperature increase was dependent on the concentration of NPs, as well as the power density of the laser (Figure 6(a,b)). Considering the enhanced effect on drug release and overall skin irritation, an NP concentration of 0.5 mg/mL and a power density of 0.5 W/cm2 were used for the in vitro experiments. The conversion stability was confirmed by conducting three on–off cycles (Figure 6(c)). Overall, the JR400-MoS2 NPs exhibited outstanding photothermal conversion ability.

Figure 6.

Figure 6.

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The heating curves of (a) JR400-MoS2 NPs of various concentrations under laser power of 0.5 W/cm2, (b) 0.5 mg/mL JR400-MoS2 NPs treated with varying laser power, and (c) temperature of the JR400-MoS2 NP solution (0.5 W/cm2, 0.5 mg/mL) over three laser cycles.

3.3. Drug loading

MoS2 nanosheets have been used as drug delivery systems, but the multilayer structure has led to compromised drug loading efficiency. The porous structure of the 3D flower-like MoS2 increases the number of drug loading sites (Yang et al., 2018). Using ATE as a model drug, higher drug concentrations yielded greater loading, with a 4:1 mass ratio of ATE to JR400-MoS2 NPs led to optimal drug loading efficiency (Figure 7). At this ratio, 1.0 g of JR400-MoS2 NPs was able to load 3.6 g of ATE, resulting in a drug loading efficiency of 361.6 ± 1.0% with 90.4 ± 0.3% of the initial drug loaded onto the NPs. An optimized concentration of 0.5 mg/mL JR400-MoS2 NPs with 2.0 mg/mL ATE was selected.

Figure 7.

Figure 7.

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Drug loading efficiency achieved as a function of the mass ratio of ATE to JR400-MoS2 NPs.

3.4. Drug release experiments

The release of ATE from the JR400-MoS2 NPs was investigated using a classic transdermal drug release study with a two-chamber diffusion cell (Sun et al., 2012). Without NIR irradiation of the JR400-MoS2 NPs, only 139.4 ± 18.17 μg/cm2 ATE was released within 48 h (Figure 8(a)). However, NIR-stimulation at 0.5 W/cm2 for 5 min caused a significant increase releasing 340.12 ± 17.84 μg/cm2 of the drug, indicating that NIR stimulation was beneficial for the release of ATE. Moreover, the use of NIR-stimulation significantly increased the release of ATE in 36 h. These results demonstrate the potential for a controllable JR400-MoS2 NP drug delivery system.

Figure 8.

Figure 8.

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(a) In vitro drug release of ATE from JR400-MoS2 NPs with (blue) and without (red) NIR stimulation. The concentration of ATE was determined via diffusion through a 0.22 μm cellulose microporous membrane. (b) In vitro skin penetration of ATE released from the JR400-MoS2 NPs with (blue) and without (red) NIR stimulation.

Nanoparticle drug delivery systems commonly use NIR stimulation to facilitate drug release. Shao et al. presented a polymeric microcapsule drug delivery system involving water-soluble antitumor drug encapsulation and GNR functionalization, where low power NIR radiation was applied to trigger the release of the drug (Shao et al., 2015). Similarly, Koning et al. developed a thermosensitive liposome drug delivery system that released the drug upon hyperthermia (Koning et al., 2010). The drug loading capacity of the JR400-MoS2 NPs was high in comparison with these other reported NPs and is expected to allow for a more sustained release of drugs.

3.5. Skin penetration study

An in vitro skin penetration assay is one way to predict drug penetration in vivo and has been validated by in vitro–in vivo correlation studies (Elmowafy et al., 2019). The amount of skin penetration in the NIR-stimulated group was 125.11 ± 8.58 μg/cm2, which was 2.3 times higher than the control, indicating that JR400-MoS2 NPs are suitable for TDDS applications (Figure 8(b)).

Transdermal penetration of small molecule drugs involves two critical steps: (1) drug release from the matrix and (2) percutaneous absorption. JR400-MoS2 NPs were not able to pass through the intact skin because of their relatively large particle, but they can easily control drug released into the matrix. Intercellular lipids of the SC are the main barrier to the penetration of drugs across the skin. The diffusion coefficient of intercellular lipids of SC could be increased by rising temperature of the skin, which could increase the mobility of the intercellular lipid (Liu et al., 2017). JR400-MoS2 NPs showed excellent photothermal conversion ability and an increased diffusion coefficient for both the drug and the intercellular lipids, resulting in increased percutaneous drug absorption (Haine et al., 2017; Teodorescu et al., 2017).

3.6. In vivo skin erythema study

Visual observation of erythema is widely used to evaluate the skin irritant potential of substances. However, this method has been criticized as imprecise and subjective. A noninvasive in vivo skin erythema measurement was used to monitor irritation caused by the JR400-MoS2 NPs. As shown in Figure 9, the ΔEI increased significantly after the topical application of 10% SDS, serving as an established positive control. Application of the JR400-MoS2 NPs suspended in water did not increase ΔEI, indicating high biocompatibility.

Figure 9.

Figure 9.

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Biocompatibility of JR400-MoS2 NPs: in vivo skin erythema study of 10% SDS, water, and JR400-MoS2 NPs.

4. Conclusions

JR400-functionalized MoS2 NPs were synthesized as a TDDS for ATE, a β1-adrenergic receptor blocking agent prescribed for hypertension. The ultra-high specific surface area of the JR400-functionalized MoS2 NPs allowed for efficient binding of ATE with 90% loading efficiency. NIR stimulation enhanced drug release and facilitated drug skin penetration. The application of JR400-MoS2 NPs as a TDDS shows the potential to mitigate issues associated with the toxicity of MoS2 use in vivo and allows for the controlled release of ATE. To our knowledge, this is the first demonstration of a functional MoS2-based TDDS. The promising results showed herein warrant further studies to evaluate the in vivo application of JR400-MoS2 NPs based TDDSs.

Funding Statement

This work was supported by Specialized Research Fund for Introducing Talents of Hebei Agricultural University (No. YJ201908), Liaoning Science and Technology [No. 20180550409], and Shenyang Medical College of Science and Technology Fund Project [No. 20186073].

Ethical approval

All the procedures were performed in accordance with the NIH Guidelines for the Care and Use of Laboratory Animals and were approved by the Animal Ethics Committee of Shenyang Medical College.

Disclosure statement

The authors declare no competing interests.

References

  1. Anselmo AC, Mitragotri S. (2014). An overview of clinical and commercial impact of drug delivery systems. J Control Release 190:15–28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Charoensumran P, Ajiro H. (2020). Controlled release of testosterone by polymer–polymer interaction enriched organogel as a novel transdermal drug delivery system: effect of limonene/PG and carbon-chain length on drug permeability. React Funct Polym 148:104461. [Google Scholar]
  3. Chen K, Wan X, Xie W, et al. (2015). Lateral built-in potential of monolayer MoS2-WS2 in-plane heterostructures by a shortcut growth strategy. Adv Mater Weinheim 27:6431–7. [DOI] [PubMed] [Google Scholar]
  4. Chng ELK, Sofer Z, Pumera M. (2014). MoS2 exhibits stronger toxicity with increased exfoliation. Nanoscale 6:14412–18. [DOI] [PubMed] [Google Scholar]
  5. Chou SS, Kaehr B, Kim J, et al. (2013). Chemically exfoliated MoS2 as near-infrared photothermal agents. Angew Chem Int Ed Engl 52:4160–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dhall R, Neupane MR, Wickramaratne D, et al. (2015). Direct bandgap transition in many-layer MoS2 by plasma-induced layer decoupling. Adv Mater Weinheim 27:1573–8. [DOI] [PubMed] [Google Scholar]
  7. Elmowafy M, Shalaby K, Ali HM, et al. (2019). Impact of nanostructured lipid carriers on dapsone delivery to the skin: in vitro and in vivo studies. Int J Pharm 572:118781. [DOI] [PubMed] [Google Scholar]
  8. Fu C, Tan L, Ren X, et al. (2018). Interlayer expansion of 2D MoS2 nanosheets for highly improved photothermal therapy of tumors in vitro and in vivo. Chem Commun (Camb) 54:13989–92. [DOI] [PubMed] [Google Scholar]
  9. Haine AT, Koga Y, Hashimoto Y, et al. (2017). Enhancement of transdermal protein delivery by photothermal effect of gold nanorods coated on polysaccharide-based hydrogel. Eur J Pharm Biopharm 119:91–5. [DOI] [PubMed] [Google Scholar]
  10. Huang B, Wang D, Wang G, et al. (2017). Enhancing the colloidal stability and surface functionality of molybdenum disulfide (MoS2) nanosheets with hyperbranched polyglycerol for photothermal therapy. J Colloid Interface Sci 508:214–21. [DOI] [PubMed] [Google Scholar]
  11. Khafaji M, Zamani M, Vossoughi M, Iraji zad A. (2019). Doxorubicin/cisplatin-loaded superparamagnetic nanoparticles as a stimuli-responsive co-delivery system for chemo-photothermal therapy. Int J Nanomedicine 14:8769–86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koning GA, Eggermont AMM, Lindner LH, Hagen TLMT. (2010). Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors. Pharm Res 27:1750–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Labouta HI, El-Khordagui LK, Kraus T, Schneider M. (2011). Mechanism and determinants of nanoparticle penetration through human skin. Nanoscale 3:4989–99. [DOI] [PubMed] [Google Scholar]
  14. Li H, Hou W, Li X. (2012). Interaction between xanthan gum and cationic cellulose JR400 in aqueous solution. Carbohydr Polym 89:24–30. [DOI] [PubMed] [Google Scholar]
  15. Liu T, Chao Y, Gao M, et al. (2016). Ultra-small MoS2 nanodots with rapid body clearance for photothermal cancer therapy. Nano Res 9:3003–17. [Google Scholar]
  16. Liu XM, Gao W, Maziarz EP, et al. (2006). Detailed characterization of cationic hydroxyethylcellulose derivatives using aqueous size-exclusion chromatography with on-line triple detection. J Chromatogr A 1104:145–53. [DOI] [PubMed] [Google Scholar]
  17. Liu C, Quan P, Li S, et al. (2017a). A systemic evaluation of drug in acrylic pressure sensitive adhesive patch in vitro and in vivo: the roles of intermolecular interaction and adhesive mobility variation in drug controlled release. J Control Release 252:83–94. [DOI] [PubMed] [Google Scholar]
  18. Liu X, Quan P, Li S, et al. (2017b). Time dependence of the enhancement effect of chemical enhancers: molecular mechanisms of enhancing kinetics. J Control Release 248:33–44. [DOI] [PubMed] [Google Scholar]
  19. Liu T, Wang C, Gu X, et al. (2014). Drug delivery with PEGylated MoS2 nano-sheets for combined photothermal and chemotherapy of cancer. Adv Mater 26:3433–40. [DOI] [PubMed] [Google Scholar]
  20. Pastore MN, Kalia YN, Horstmann M, Roberts MS. (2015). Transdermal patches: history, development and pharmacology. Br J Pharmacol 172:2179–209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Qiao X, Hu F, Hou D, Li D. (2016). PEG assisted hydrothermal synthesis of hierarchical MoS2 microspheres with excellent adsorption behavior. Mater Lett 169:241–5. [Google Scholar]
  22. Ran F, Zou Y, Xu Y, et al. (2019). Fe3O4 @MoS2 @PEI-facilitated enzyme tethering for efficient removal of persistent organic pollutants in water. Chem Eng J 375:121947. [Google Scholar]
  23. Shao J, Xuan M, Si T, et al. (2015). Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release. Nanoscale 7:19092–8. [DOI] [PubMed] [Google Scholar]
  24. Sun L, Cun D, Yuan B, et al. (2012). Formulation and in vitro/in vivo correlation of a drug-in-adhesive transdermal patch containing azasetron. J Pharm Sci 101:4540–8. [DOI] [PubMed] [Google Scholar]
  25. Tang G, Sun J, Wei C, et al. (2012). Synthesis and characterization of flowerlike MoS2 nanostructures through CTAB-assisted hydrothermal process. Mater Lett 86:9–12. [Google Scholar]
  26. Tang G, Wang Y, Chen W, et al. (2013). Hydrothermal synthesis and characterization of novel flowerlike MoS2 hollow microspheres. Mater Lett 100:15–18. [Google Scholar]
  27. Teodorescu F, Quéniat G, Foulon C, et al. (2017). Transdermal skin patch based on reduced graphene oxide: a new approach for photothermal triggered permeation of ondansetron across porcine skin. J Control Release 245:137–46. [DOI] [PubMed] [Google Scholar]
  28. Wang J, Zhu M, Chen Z, et al. (2019). Polyacrylamide modified molybdenum disulfide composites for efficient removal of graphene oxide from aqueous solutions. Chem Eng J 361:651–9. [Google Scholar]
  29. Wang S, Chen Y, Li X, et al. (2015). Injectable 2D MoS2-integrated drug delivering implant for highly efficient NIR-triggered synergistic tumor hyperthermia. Adv Mater 27:7117–22. [DOI] [PubMed] [Google Scholar]
  30. Wang S, Li X, Chen Y, et al. (2015). A facile one-pot synthesis of a two-dimensional MoS2/Bi2S3 composite theranostic nanosystem for multi-modality tumor imaging and therapy. Adv Mater 27:2775–82. [DOI] [PubMed] [Google Scholar]
  31. Wu B, Chen L, Wu X, et al. (2019). Differential influence of molybdenum disulfide at the nanometer and micron scales in the intestinal metabolome and microbiome of mice. Environ Sci Nano 6:1594–606. [Google Scholar]
  32. Wu J, Bremner DH, Niu S, et al. (2018). Functionalized MoS2 nanosheet-capped periodic mesoporous organosilicas as a multifunctional platform for synergistic targeted chemo-photothermal therapy. Chem Eng J 342:90–102. [Google Scholar]
  33. Yang H, Zhao J, Wu C, et al. (2018). Facile synthesis of stable colloidal MoS2 nanoparticles for combined tumor therapy. Chem Eng J 351:548–58. [Google Scholar]
  34. Yin W, Yan L, Yu J, et al. (2014). High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared photothermal-triggered drug delivery for effective cancer therapy. ACS Nano 8:6922–33. [DOI] [PubMed] [Google Scholar]
  35. Yu Y, Yi Y, Li Y, et al. (2018). Dispersible MoS2 micro-sheets induced a proinflammatory response and apoptosis in the gills and liver of adult zebrafish. RSC Adv 8:17826–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zhang A, Li A, Zhao W, et al. (2018). An efficient and self-guided chemo-photothermal drug loading system based on copolymer and transferrin decorated MoS2 nanodots for dually controlled drug release. Chem Eng J 342:120–32. [Google Scholar]
  37. Zhang X, Huang X, Xue M, et al. (2015). Hydrothermal synthesis and characterization of 3D flower-like MoS2 microspheres. Mater Lett 148:67–70. [Google Scholar]
  38. Zhang Y, Chen P, Wen F, et al. (2016). Fe3O4 nanospheres on MoS2 nanoflake: electrocatalysis and detection of Cr (VI) and nitrite. J Electroanal Chem 761:14–20. [Google Scholar]
  39. Zhang Y, Xiu W, Sun Y, et al. (2017). RGD-QD-MoS2 nanosheets for targeted fluorescent imaging and photothermal therapy of cancer. Nanoscale 9:15835–45. [DOI] [PubMed] [Google Scholar]
  40. Zhu C, Zeng Z, Li H, et al. (2013). Single-layer MoS2-based nanoprobes for homogeneous detection of biomolecules. J Am Chem Soc 135:5998–6001. [DOI] [PubMed] [Google Scholar]

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