Aptamer-functionalized molybdenum disulfide nanosheets for tumor cell targeting and lysosomal acidic environment/NIR laser responsive drug delivery to realize synergetic chemo-photothermal therapeutic effects.

Molybdenum disulfide (MoS2), one representative 2D nanomaterial, has recently emerged as a unique platform in the biomedical field. However, its application in drug delivery systems should be further exploited. Here, we report a novel tumor cell targeting and lysosomal acidic environment/NIR laser dual responsive drug delivery system for synergetic chemo-photothermal treatment of cancer cells. The MoS2 nanosheets were loaded with chemotherapy drug doxorubicin (DOX) and coated with polydopamine (PDA) layer. Then, thiolated aptamer AS1411 and polyethylene glycol (PEG) were modified onto MoS2 nanosheets through Michael addition reaction to construct DOX@Apt-PEG-PDA-MoS2 nanosheets. The aptamer modification endowed the nanoplatform with targeting ability to breast cancer MCF-7 cells. MoS2 and PDA converted 808 nm NIR laser into heat and played the role of photothermal therapy (PTT). Tumor lysosomal acidic environment and NIR laser irradiation accelerated the release of DOX from the nanosheets. The nanocarrier Apt-PEG-PDA-MoS2 showed good biocompatibility, and DOX@Apt-PEG-PDA-MoS2 showed synergetic chemo-photothermal therapy effects with significantly enhanced anti-tumor efficacy, suggesting that this MoS2-based drug delivery platform is promising for targeted and synergetic treatment of cancer.

Cai S ，Yan J ，Xiong H ，Wu Q ，Xing H ，Liu Y ，Liu S ，Liu Z ... -  《-》

A multifunctional nanoplatform based on MoS(2)-nanosheets for targeted drug delivery and chemo-photothermal therapy.

Synergistic tumor treatment has recently attracted more and more attention due to its remarkable therapeutic effect. Herein, a multifunctional drug delivery system based on hyaluronic acid (HA) targeted dual stimulation responsive MoS2 nanosheets (HA-PEI-LA-MoS2-PEG, HPMP) for active interaction with CD44 receptor positive MCF-7 cells is reported. Melanin (Mel), a new type of photothermal agent and doxorubicin (DOX) are both loaded onto the HPMP nanocomposite and can be released by mild acid or hyperthermia. The prepared HPMP nanocomposite has a uniform hydrodynamic diameter (104 nm), a high drug loading (944.3 mg.g-1 HPMP), a remarkable photothermal effect (photothermal conversion efficiency: 55.3%) and excellent biocompatibility. The DOX release from HPMP@(DOX/Mel) can be precisely controlled by the dual stimuli of utilizing the acidic environment in the tumor cells and external laser irradiation. Meanwhile, loading of Mel onto the surface can enhance the photothermal effect of the MoS2 nanosheets. In vitro experiments showed that the HPMP@(DOX/Mel) nanoplatform could efficiently deliver DOX into MCF-7 cells and demonstrated enhanced cytotoxicity compared to that of the non-targeted nanoplatform. In vivo experiments in a breast cancer model of nude mice further confirmed that the HPMP@(DOX/Mel) significantly inhibited tumor growth under near infrared (NIR) laser irradiation, which is superior to any single therapy. In summary, this flexible nanoplatform, based on multi-faceted loaded MoS2 nanosheets, exhibits considerable potential for efficient pH/NIR-responsive targeted drug delivery and chemo-photothermal synergistic tumor therapy.

Yang Y ，Wu J ，Bremner DH ，Niu S ，Li Y ，Zhang X ，Xie X ，Zhu LM ... -  《-》

Dual-responsive molybdenum disulfide/copper sulfide-based delivery systems for enhanced chemo-photothermal therapy.

Molybdenum disulfide (MoS2)-based drug delivery systems have shown considerable potential in cancer nanomedicines. In this work, a multifunctional nanoplatform comprising MoS2 nanosheets decorated with copper sulfide (CuS) and further functionalized with polyethylene glycol (PEG) is reported. The resultant material has a particle size of approximately 115 nm, and can be loaded with doxorubicin (DOX) to a loading capacity of 162.3 mg DOX per g of carrier. Drug release is triggered by two stimuli (near infrared (NIR) irradiation and pH), and the carrier is shown to have excellent colloidal stability. The presence of both MoS2 and CuS leads to very high photothermal conversion efficiency (higher than with MoS2 alone). In vitro experiments revealed that the blank CuS-MoS2-SH-PEG carrier is biocompatible, but that the synergistic application of chemo-photothermal therapy (in the form of CuS-MoS2-SH-PEG loaded with DOX and NIR irradiation) led to greater cell death than either chemotherapy (CuS-MoS2-SH-PEG(DOX) but no NIR) or photothermal therapy (CuS-MoS2-SH-PEG with NIR). A cellular uptake study demonstrated that the nanoplatform can efficiently enter tumor cells, and that uptake is enhanced when NIR is applied. Overall, the functionalized MoS2 material developed in this work exhibits great potential as an efficient system for dual responsive drug delivery and synergistic chemo-photothermal therapy. The route employed in our work thus provides a strategy to enhance photothermal efficacy for transition metal dichalcogenide drug delivery systems.

Zhang X ，Wu J ，Williams GR ，Yang Y ，Niu S ，Qian Q ，Zhu LM ... -  《-》

Functionalized MoS(2)-nanosheets for targeted drug delivery and chemo-photothermal therapy.

Molybdenum disulfide (MoS2) has been extensively explored for biomedical applications due to its excellent photothermal conversion ability. In this paper, we report a nanoplatform based on folic acid (FA) targeted dual-stimuli responsive MoS2 nanosheets and explore this for the treatment of FA-receptor positive human breast cancer. The nanocomposites generated had a uniform diameter (ca. 133 nm), and could be loaded with the anti-cancer drug doxorubicin (DOX) to a high capacity (151.4 mg/g). The release of DOX was greatly accelerated at pH 5.0 as compared to pH 7.4. In addition, it was found that drug release is enhanced under near infrared laser (NIR) irradiation, showing that the composites can be used as dual responsive systems, with DOX release controllable through pH or NIR irradiation. MTT assays and confocal experiments showed that the MoS2-based nanoplatform could selectively target and kill FA-positive MDA-MB-231 cells (a human breast cancer cell line). The platform also allowed the combination of chemotherapy and photothermal therapy, which led to synergistic effects superior to either monotherapy. The functionalized MoS2 nanoplatform developed in this work hence could be a potent system for targeted drug delivery and synergistic chemo-photothermal cancer therapy.

Zhang X ，Wu J ，Williams GR ，Niu S ，Qian Q ，Zhu LM ... -  《-》

Functionalized MoS(2)-erlotinib produces hyperthermia under NIR.

Zhang C ，Zhang D ，Liu J ，Wang J ，Lu Y ，Zheng J ，Li B ，Jia L ... -  《JOURNAL OF NANOBIOTECHNOLOGY》