Abstract

BackgroundThe construction of a multifunctional drug delivery system with a variety of advantageous features, including targeted delivery, controlled release and combined therapy, is highly attractive but remains a challenge.ResultsIn this study, we developed a MoS2-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving targeted delivery of camptothecin (CPT) and dual-stimuli-responsive drug release. HA was connected to MoS2 via a disulfide linkage, forming a sheddable HA shell on the surface of MoS2. This unique design not only effectively prevented the encapsulated CPT from randomly leaking during blood circulation but also significantly accelerated the drug release in response to tumor-associated glutathione (GSH). Moreover, the MoS2-based generated heat upon near-infrared (NIR) irradiation could further increase the drug release rate as well as induce photothermal ablation of cancer cells. The results of in vitro and in vivo experiments revealed that MoS2–SS–HA–CPT effectively suppressed cell proliferation and inhibited tumor growth in lung cancer cell-bearing mice under NIR irradiation via synergetic chemo-photothermal therapy.ConclusionsThe as-prepared MoS2–SS–HA–CPT with high targeting ability, dual-stimuli-responsive drug release, and synergistic chemo-photothermal therapy may provide a new strategy for cancer therapy.

Highlights

  • Cancer has already been proven to be a major threat to human health, with more than eight million cancerrelated deaths each year worldwide [1]

  • hyaluronic acid (HA) can form a shell on the surface of ­MoS2 nanosheets after HA coating, similar to graphene oxide (GO), and this shell can restrict the release of the loaded drug, which seriously reduces the therapeutic efficacy of the nanosheets [34]

  • The preparation of redox-sensitive ­MoS2-based HA-functionalized nanosheets was divided into two steps: first, cystamine was conjugated via EDC/NHS coupling, and DTT was used to generate free thiol groups in the backbone of HA by cleaving the disulfide linkage in the conjugated cystamine moiety; second, the thiolated HA was coupled to the ­MoS2 nanosheets by forming disulfide bonds

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Summary

Results

We developed a ­MoS2-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving targeted delivery of camptothecin (CPT) and dual-stimuli-responsive drug release. HA was connected to ­MoS2 via a disulfide linkage, forming a sheddable HA shell on the surface of M­ oS2. This unique design effectively prevented the encapsulated CPT from randomly leaking during blood circulation and significantly accelerated the drug release in response to tumor-associated glutathione (GSH). The M­ oS2-based generated heat upon near-infrared (NIR) irradiation could further increase the drug release rate as well as induce photothermal ablation of cancer cells. The results of in vitro and in vivo experiments revealed that M­ oS2–SS–HA–CPT effectively suppressed cell proliferation and inhibited tumor growth in lung cancer cell-bearing mice under NIR irradiation via synergetic chemo-photothermal therapy

Conclusions
Introduction
Results and discussion

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