Specific generation of reactive oxygen species (ROS) within tumors in situ catalyzed by nanozymes is a promising strategy for cancer therapeutics. However, it remains a significant challenge to fabricate highly efficient nanozymes acting in the tumor microenvironment. Herein, we develop a bimetallic nanozyme (Pt50Sn50) with the photothermal enhancement of dual enzymatic activities for tumor catalytic therapy. The structures and activities of PtSn bimetallic nanoclusters (BNCs) with different Sn content are explored and evaluated systematically. Experimental comparisons show that the Pt50Sn50 BNCs exhibit the highest activities among all those investigated, including enzymatic activity and photothermal property, due to the generation of SnO2-x with oxygen vacancy (Ovac) sites on the surface of Pt50Sn50 BNCs. Specifically, the Pt50Sn50 BNCs exhibit photothermal-enhanced peroxidase-like and catalase-like activities, as well as a significantly enhanced anticancer efficacy in both multicellular tumor spheroids and in vivo experiments. Due to the high X-ray attenuation coefficient and excellent light absorption property, the Pt50Sn50 BNCs also show dual-mode imaging capacity of computed tomography and photoacoustic imaging, which could achieve in vivo real-time monitoring of the therapeutic process. Therefore, this work will advance the development of noble-metal nanozymes with optimal composition for efficient tumor catalytic therapy.

Dual Nanozyme-Driven PtSn Bimetallic Nanoclusters for Metal-Enhanced Tumor Photothermal and Catalytic Therapy.

Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects. Currently, the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene therapy. For this purpose, stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection, prolonged blood circulation, specific tumor accumulation, and controlled release profile of nucleic acid drugs. Besides, synergistic therapy could be achieved when combined with other therapeutic regimens. This review summarizes recent advances in various stimuli-responsive nanocarriers for gene delivery. Particularly, the nanocarriers responding to endogenous stimuli including pH, reactive oxygen species, glutathione, and enzyme, etc., and exogenous stimuli including light, thermo, ultrasound, magnetic field, etc., are introduced. Finally, the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well discussed. The major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable. 

/pdf/stimuli-responsive-gene-delivery-nanocarriers-for-cancer-3dv2kdv0.pdf

Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy

Immune checkpoint blockade (ICB) therapy shows excellent efficacy against malignancies; however, insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment (TME) are considered as the two major stumbling blocks to a broad ICB response. Here, a combinational therapeutic strategy is reported, wherein TME‐reactive oxygen species/pH dual‐responsive signal transducers and activators of transcription 3 inhibitor nanoprodrugs MPNPs are combined with oncolytic herpes simplex virus 1 virotherapy to synergistically ignite pyroptosis for enhancing immunotherapy. MPNPs exhibit a certain level of tumor accumulation, reduce tumor cell stemness, and enhance antitumor immune responses. Furthermore, the simultaneous application of oncolytic viruses (OVs) confers MPNPs with higher tumor penetration capacity and remarkable gasdermin‐E‐mediated pyroptosis, thereby reshaping the TME and transforming “cold” tumors into “hot” ones. This “fire of immunity” strategy successfully activates robust T‐cell‐dependent antitumor responses, potentiating ICB effects against local recurrence and pulmonary metastasis in preclinical “cold” murine triple‐negative breast cancer and syngeneic oral cancer models. Collectively, this work may pave a new way and offer an unprecedented opportunity for the combination of OVs with nanomedicine for cancer immunotherapy.

A Dual‐Responsive STAT3 Inhibitor Nanoprodrug Combined with Oncolytic Virus Elicits Synergistic Antitumor Immune Responses by Igniting Pyroptosis

Two-Dimensional Nanomaterial-based Catalytic Medicine: Theories, Advanced Catalyst and System Design.

The biochemical indicators of tumor microenvironment (TME) that are different from normal tissues provide the possibility for constructing intelligent drug delivery systems (DDSs). Polysaccharides with good biocompatibility, biodegradability, and unique biological properties are ideal materials for constructing DDSs. Nanogels, micelles, organic-inorganic nanocomposites, hydrogels, and microneedles (MNs) are common polysaccharide-based DDSs. Polysaccharide-based DDSs enable precise control of drug delivery and release processes by incorporating TME-specific biochemical indicators. The classification and design strategies of polysaccharide-based TME-responsive DDSs are comprehensively reviewed. The advantages and challenges of current polysaccharide-based DDSs are summarized and the future directions of development are foreseen. The polysaccharide-based TME-responsive DDSs are expected to provide new strategies and solutions for cancer therapy and make important contributions to the realization of precision medicine. 

Polysaccharide-based tumor microenvironment-responsive drug delivery systems for cancer therapy.

Tumor microenvironment-responsive dynamic inorganic nanoassemblies for cancer imaging and treatment.

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Tumor microenvironment-responsive dynamic inorganic nanoassemblies for cancer imaging and treatment.