Although phototherapy has been considered as an emerging and promising technology for cancer therapy, its therapeutic specificity and efficacy are severely limited by nonspecific uptake by normal tissues, tumor hypoxia, and so on. Herein, combination-responsive strategy (CRS) is applied to develop one kind of hyaluronic acid-hybridized Ru nanoaggregates (HA-Ru NAs) for enhanced cancer phototherapy via the reasonable integration of receptor-mediated targeting (RMT) and tumor-microenvironment responsiveness (TMR). In this nanosystem, the HA component endows HA-Ru NAs with RMT characteristic to selectively recognize CD44-overexpressing cancer cells, whereas the Ru nanocomponent makes HA-Ru NAs have TMR therapy activity. Specially, the Ru nanocomponent not only has near-infrared-mediated photothermal and photodynamic functions but also can catalyze H2O2 in tumor tissue to produce O2 for the alleviation of tumor hypoxia and toxic •OH for chemodynamic therapy. Benefitting from these, HA-Ru NAs can be considered as a promising kind of CRS nanoplatforms for synergistic photothermal/photodynamic/chemodynamic therapies of cancer, which will not only effectively improve the phototherapeutic specificity and efficacy but also simplify the therapeutic nanosystems. Meanwhile, HA-Ru NAs can serve as a photoacoustic and computed tomography imaging contrast agent to monitor tumors. Such CRS nanoplatforms hold significant potential in improving therapeutic specificity and efficacy for enhanced cancer phototheranostics.

The selection of suitable nanozymes with easy synthesis, tumor specificity,m ultifunction,a nd high therapeutics is meaningful for tumor therapy.H erein, af acile onestep assembly approach was employed to successfully prepare an ovel kind of naturalp olyphenol tannic acid (TA) hybrid with mixed valence vanadium oxide nanosheets (TA@VO x NSs). In this system, VO x is assembled with TA through metal-phenolic coordination interaction to both introduce superior peroxidase-like activity and high near infrared (NIR) absorption owing to partial reduction of vanadium from V 5 + to V 4 + .T he presence of mixed valencev anadium oxide in TA@VO x NSs is proved to be the key for the catalytic reaction of hydrogen peroxide (H 2 O 2)t oCOH, and the corre-spondingc atalytic mechanism of H 2 O 2 by TA@VO x NSsi s proposed. Benefitting from such peroxidase-like activity of TA@VO x NSs, the overproduced H 2 O 2 of the tumor microenvironmenta llows the realization of tumor-specific chemodynamic therapy (CDT). As av alid supplementt oC DT,t he NIR absorption enables TA@VO x NSs to have NIR light-mediated conversion ability for photothermal therapy(PTT) of cancers. Furthermore, in vitro and in vivo experimentsc onfirmed that TA@VO x NSs can effectively inhibit the growth of tumors by synergistic CDT/PTT.T hese resultso ffer ap romising way to develop novel vanadium oxide-based nanozymes for enhanced synergistic tumor-specific treatment.

A WO3−x-based nanotheranostic has been successfully fabricated for photoacoustic imaging-guided synergistic tumor targeting therapy in the second near-infrared (NIR-II) biological window.

Photoimmunotherapy (PIT) has shown enormous potential in not only eliminating primary tumors, but also inhibiting abscopal tumor growth. However, the efficacy of PIT is greatly limited by tumor hypoxia, which causes the attenuation of phototherapeutic efficacy and is a feature of the immunosuppressive tumor microenvironment (TME). In this study, one type of brand‐new artificial metalloprotein nanoanalogues is developed via reasonable integration of a “phototherapy‐enzymatic” RuO2 and a model antigen, ovalbumin (OVA) for enhanced PIT of cancers, namely, RuO2‐hybridized OVA nanoanalogues (RuO2@OVA NAs). The RuO2@OVA NAs exhibit remarkable photothermal/photodynamic capabilities under the near‐infrared light irradiation. More importantly, the photoacoustic imaging and immunofluorescence staining confirm that RuO2@OVA NAs can remarkably alleviate hypoxia via in situ catalysis of hydrogen peroxide overexpressed in the TME to produce oxygen (O2). This ushers a prospect of concurrently enhancing photodynamic therapy and reversing the immunosuppressive TME. Also, OVA, as a supplement to the immune stimulation induced by phototherapy, can activate immune responses. Finally, further combination with the cytotoxic T‐lymphocyte‐associated protein 4 checkpoint blockade is reported to effectively eliminate the primary tumor and inhibit distant tumor growth via the abscopal effect of antitumor immune responses, prolonging the survival.

Recently, inorganic nanomaterials have received considerable attention for use in biomedical applications owing to their unique physicochemical properties based on their shapes, sizes, and surface characteristics. Photodynamic therapy (PDT), sonodynamic therapy (SDT), and chemical dynamic therapy (CDT), which are cancer therapeutics mediated by reactive oxygen species (ROS), have the potential to significantly enhance the therapeutic precision and efficacy for cancer. To facilitate cancer therapeutics, numerous inorganic nanomaterials have been developed to generate ROS. This mini review provides an overview of the generation mechanisms of ROS by representative inorganic nanomaterials for cancer therapeutics, including the structures of engineered inorganic nanomaterials, ROS production conditions, ROS types, and the applications of the inorganic nanomaterials in cancer PDT, SDT, and CDT.