Biomedical Materials For Combined Chemo-Photothermal Antitumor And Tumor Vaccine Delivery

At present,malignant tumors are serious threat to human health and life.Traditional methods of tumor treatment（surgical resection,radiation therapy,and chemotherapy）have different limitations,although they have achieved certain therapeutic effects in clinic.In recent years,with the great advances in modern nanomedicine and biotechnology,the development of new treatments has been promoted,such as immunotherapy,photodynamic therapy,and combination therapy.These new therapies have achieved breakthroughs in different degrees in the laboratory or clinically,allowing us to see the dawn of a complete cure for tumors.In this paper,we mainly studied combined chemo-photothermal antitumor therapy using molybdenum disulfide modified with hyperbranched polyglycidyl,and cell penetrating peptide-based redox-sensitive vaccine delivery system for subcutaneous vaccination.1 Combined Chemo-photothermal Antitumor Therapy Using Molybdenum Disulfide Modified with Hyperbranched PolyglycidylIn the treatment of cancers,molybdenum disulfide（MoS₂）has shown great potential as a photoabsorbing agent in photothermal therapy and also as an antitumor drug delivery system in chemotherapy.However,the poor dispersibility and stability of MoS₂ in aqueous solutions limit its applications in cancer therapy.To overcome the shortcomings,MoS₂was modified mainly by surface adsorption of linear polymers,such as chitosan and poly（ethylene glycol）.As reported,the linear polymers could be more rapidly cleared from blood circulation than their branched counterparts.Herein,we developed hyperbranched polyglycidyl（HPG）modified MoS₂（MoS₂-HPG）by absorbing HPG on the MoS₂ surface.The MoS₂-HPG as a novel photoabsorbing agent was also used as a nanoscaled carrier to load antitumor drug doxorubicin hydrochloride（DOX）（MoS₂-HPG-DOX）for combined chemo-photothermal therapy.The physicochemical and photothermal properties of MoS₂-HPG were measured,and the results indicate that MoS₂-HPG had good dispersion and stability in aqueous solutions and also high photothermal conversion efficiency.MoS₂-HPG displayed good biocompatibility in hemocompatibility and cytotoxicity evaluations in vitro.Furthermore,the combined chemo-photothermal therapy using MoS₂-HPG-DOX demonstrated better anticancer effect than the individual chemotherapy or photothermal therapy alone.From the results,MoS₂-HPG with combined chemo-photothermal therapy could be developed as a promising therapeutic formulation for clinical cancer treatment.2 Cell penetrating peptides-based redox-sensitive vaccine delivery system for subcutaneous vaccinationIn immunotherapy,induction of potent cellular immunity by vaccination is essential to treat intracellular infectious diseases and tumors.In this work,we designed a new synthetic peptide carrier Cys-Trp-Trp-Arg₈-Cys-Arg₈-Cys-Arg₈-Cys for vaccine delivery by integrating redox-responsive disulfide bond cross-linking and cell-penetrating peptide Arginine octamer.The carrier peptide bound to antigen protein ovalbumin（OVA）via electrostatic self-assembly to form peptide/OVA nanocomposites.Then,the spontaneous oxidization of the thiols of the cysteine residues induced interpeptide disulfide bond crosslinking to construct denser peptide/OVA condensates.The cell-penetrating peptides incorporated in the carrier peptide could increase antigen uptake by antigen presenting cells.After internalized by antigen presenting cells,the antigen could be rapidly released in cytoplasm along with degradation of the disulfide bonds by intracellular glutathione,which could promote potent CD8⁺T cell immunity.The cross-linked peptide/OVA condensates were used for subcutaneous vaccination.The results showed that,the peptide carrier mediated potent antigen-specific immune response by significantly increasing IgG titer,splenocyte proliferation,secretion level of cytokines IFN-γ,IL-12,IL-4 and IL-10,immune memory function,and activation and maturation of dendritic cells.From the results,the low molecular weight vaccine condensing peptide with definite chemical composition could be developed as a novel class of vaccine delivery systems.