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.

Tumor microenvironment and NIR laser dual-responsive release of berberine 9-O-pyrazole alkyl derivative loaded in graphene oxide nanosheets for chemo-photothermal synergetic cancer therapy.

A berberine 9-O-pyrazole alkyl derivative, a chemical compound (called B3) previously synthesized by our group, shows anti-cancer activity. However, B3 lacks targeting cytotoxicity to cancer cells, leading to obvious toxic side effects on normal cells. To solve this problem, here, we prepared a drug delivery system, namely, AS1411-GO/B3 for tumor targeting, in which nano-graphene oxide (GO) sheets were employed as the drug carrier, and the aptamer AS1411 was conjugated onto GO for tumor targeting. GO also had a photothermal effect, which helped the release of B3 from GO as well as the thermal cytotoxicity to cells. We found that the release of B3 could respond to acid conditions, indicating that the tumor intracellular environment could promote the release of B3, thus allowing it to perform chemotherapy effects. This system could also release B3 in response to photothermal heating, moreover, combined photothermal therapy and chemotherapy to improve the anticancer activity was achieved. This AS1411-GO/B3 platform with chemo-photothermal synergetic therapy provides a very promising treatment for tumors.