The microenvironment of hypoxia and immune-cold limits the therapeutic outcomes of immune checkpoint blockade (ICB) therapy in solid tumors. It is important and imperative to search new strategies to relieve tumor hypoxia and reverse immunosuppression of cold tumors. In this study, the oxygen (O₂) self-replenishing nano-enabled coordination platform can be used to induce potent antitumor immune response in cold tumors. The nanoplatform can produce O₂ by catalyzing hydrogen peroxide (H₂O₂) in tumor site effectively, showing excellent photodynamic therapy (PDT) performance. Meanwhile, it can further trigger immunogenic cell death (ICD), enhance T cell infiltration, reverse immunosuppression, and reprogram the immune-cold tumor microenvironment. In vitro and in vivo results demonstrate that the nanoplatform has potential for eradicating tumors and long-term immunological memory effect. The nanoplatform opens up a strategy for reprograming the immunosuppressive microenvironment in cold tumors.

A bioresponsive polymeric nanocarrier for drug delivery is able to alter its physical and physicochemical properties in response to a variety of biological signals and pathological changes, and can exert its therapeutic efficacy within a confined space. These nanosystems can optimize the biodistribution and subcellular location of therapeutics by exploiting the differences in biochemical properties between tumors and normal tissues. Moreover, bioresponsive polymer-based nanosystems could be rationally designed as precision therapeutic platforms by optimizing the combination of responsive elements and therapeutic components according to the patient-specific disease type and stage. In this review, recent advances in smart bioresponsive polymeric nanosystems for cancer chemotherapy and immunotherapy will be summarized. We mainly discuss three categories, including acidity-sensitive, redox-responsive, and enzyme-triggered polymeric nanosystems. The important issues regarding clinical translation such as reproducibility, manufacture, and probable toxicity, are also commented.