Figure 17. Optimization of graphene-based photothermal agents. (a) AFM images of different graphene derivatives: while nGO-PEG and nRGO-PEG showed similar ultrasmall sizes at about 20−30 nm, the size of RGO-PEG was about 60−70 nm. Insets are photos of the respective solutions. RGO-PEG and nRGO-PEG showed much enhanced optical absorbance as compared to nGO-PEG. (b) The blood circulation of GO derivatives measured by collecting blood from mice iv injected with 125 I labeled nGO-PEG, nRGO-PEG, and RGO-PEG at various time points (n = 3). (c) The biodistribution of GO derivatives in 4T1 tumor-bearing mice 2 days after injection. The radioactivities in tissue and blood samples were determined by a gamma counter. (d) The 4T1 tumor growth curves of mice after various treatments indicated. The laser irradiation was conducted at the power density of 0.15 W/cm 2 for 5 min. (e) Survival of tumor-bearing mice after various treatments indicated. Reprinted with permission from ref 169.

A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

MoS2 nanosheets functionalized with poly-ethylene glycol are for the first time used as a multifunctional drug delivery system with high drug loading capacities. Using doxorubicin as the model drug and taking advantages of the strong near-infrared absorbance of MoS2, combined photothermal and chemotherapy of cancer is realized in animal experiments, achieving excellent synergistic anti-tumor effect upon systemic administration.

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core–shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.

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Despite recent advances in melanoma treatment through the use of anti-PD-1 (aPD1) immunotherapy, the efficacy of this method remains to be improved. Here we report an innovative self-degradable microneedle (MN) patch for the sustained delivery of aPD1 in a physiologically controllable manner. The microneedle is composed of biocompatible hyaluronic acid integrated with pH-sensitive dextran nanoparticles (NPs) that encapsulate aPD1 and glucose oxidase (GOx), which converts blood glucose to gluconic acid. The generation of acidic environment promotes the self-dissociation of NPs and subsequently results in the substantial release of aPD1. We find that a single administration of the MN patch induces robust immune responses in a B16F10 mouse melanoma model compared to MN without degradation trigger or intratumoral injection of free aPD1 with the same dose. Moreover, this administration strategy can integrate with other immunomodulators (such as anti-CTLA-4) to achieve combination therapy for enhancing antitumor efficacy.

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