Symphony of nanomaterials and immunotherapy based on the cancer-immunity cycle

The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death(ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators.Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.

pH-Sensitive nanoscale materials as robust drug delivery systems for cancer therapy

Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lacking selectivity and causing severe side effects.According to detailed researches on the metabolism,functions and histology of cancer tissues,many different features of cancer are uncovered,like lower pH in microenvironment,abnormal redox level in intracellular compartments and elevated expression level of several enzymes and receptors.Recently,the development of smart nanoparticles that response to tumor specific microenvironment has lighted up hope for selective cancer therapy.Herein,this review mainly focuses on pH-sensitive nano scale materials for anti-cancer drug delivery.We summarized the formation progress of acidic tumor microenvironment,the mechanism of pHresponsive drug delivery system and nanomaterials that responsive to acidic pH in tumor microenvironment.

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.