Biodegradable calcium sulfide-based nanomodulators for H_(2)S-boosted Ca^(2+)-involved synergistic cascade cancer therapy

Hydrogen sulfide(H_(2)S)is the most recently discovered gasotransmitter molecule that activates multiple intracellular signaling pathways and exerts concentration-dependent antitumor effect by interfering with mitochondrial respiration and inhibiting cellular ATP generation.Inspired by the fact that H_(2)S can also serve as a promoter for intracellular Ca^(2+)influx,tumor-specific nanomodulators(I-CaS@PP)have been constructed by encapsulating calcium sulfide(CaS)and indocyanine green(ICG)into methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide)(PLGA-PEG).I-CaS@PP can achieve tumor-specific biodegradability with high biocompatibility and pH-responsive H_(2)S release.The released H_(2)S can effectively suppress the catalase(CAT)activity and synergize with released Ca^(2+)to facilitate abnormal Ca^(2+)retention in cells,thus leading to mitochondria destruction and amplification of oxidative stress.Mitochondrial dysfunction further contributes to blocking ATP synthesis and downregulating heat shock proteins(HSPs)expression,which is beneficial to overcome the heat endurance of tumor cells and strengthen ICG-induced photothermal performance.Such a H_(2)S-boosted Ca^(2+)-involved tumor-specific therapy exhibits highly effective tumor inhibition effect with almost complete elimination within 14-day treatment,indicating the great prospect of CaS-based nanomodulators as antitumor therapeutics.

Bioinspired membrane-based nanomodulators for immunotherapy of autoimmune and infectious diseases

Autoimmune or infectious diseases often instigate the undesirable damages to tissues or organs to trigger immune-related diseases,which involve plenty of immune cells,pathogens and autoantibodies.Nanomedicine has a great potential in modulating immune system.Particularly,biomimetic nanomodulators can be designed for prevention,diagnosis and therapy to achieve a better targeted immunotherapy.With the development of materials science and bioengineering,a wide range of membranecoated nanomodulators are available.Herein,we summarize recent advancements of bioinspired membrane-coated nanoplatform for systemic protection against immune-related diseases including autoimmune and infectious diseases.We also rethink the challenges or limitations in the progress of the therapeutic nanoplatform,and discuss the further application of the nanomodulators in the view of translational medicine for combating immune-related diseases.