Nan Yang

Purpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer. Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)–modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO 2 @ICG NP. In this structure, the HMnO 2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O 2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects. Results: Mn 2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO 2 @ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO 2 @ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility. Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer. Keywords: phototherapy, reactive oxygen species, hypoxia relief, collaborative therapy

Abstract Photodynamic therapy (PDT), as one of the noninvasive clinical cancer phototherapies, suffers from the key drawback associated with hypoxia at the tumor microenvironment (TME), which plays an important role in protecting tumor cells from damage caused by common treatments. High concentration of hydrogen peroxide (H 2 O 2 ), one of the hallmarks of TME, has been recognized as a double-edged sword, posing both challenges, and opportunities for cancer therapy. The promising perspectives, strategies, and approaches for enhanced tumor therapies, including PDT, have been developed based on the fast advances in H 2 O 2 -enabled theranostic nanomedicine. In this review, we outline the latest advances in H 2 O 2 -responsive materials, including organic and inorganic materials for enhanced PDT. Finally, the challenges and opportunities for further research on H 2 O 2 -responsive anticancer agents are envisioned.

Fenton and Fenton-like reactions. Without external stimulus and drug resistance generation, reactive oxygen species (ROS)-mediated CDT exhibits a specific and desirable anticancer effect and has been seen as a promising strategy for cancer therapy. However, optimizing the treatment efficiency of CDT in TME is still challenging because of the limited catalytic efficiency of CDT agents and the strong cancer antioxidant capacity in TME. Hence, scientists are trying their best to design and fabricate many more CDT agents with excellent catalytic activity and remodeling TME for optimal CDT. In this perspective, the latest progress of CDT is discussed, with some representative examples presented. Consequently, promising strategies for further optimizing the efficiency of CDT guided by Fenton chemistry are provided. Most importantly, several feasible ways of developing CDT in the future are offered for reference.

Abstract Catalytic cancer therapy based on nanozymes has recently attracted much interest. However, the types of the current nanozymes are limited and their efficiency is usually compromised and not sustainable in the tumor microenvironment (TME). Therefore, combination therapy involving additional therapeutics is often necessary and the resulting complication may jeopardize the practical feasibility. Herein, an unprecedented “all‐in‐one” Fe 3 O 4 /Ag/Bi 2 MoO 6 nanoparticle (FAB NP) is rationally devised to achieve synergistic chemodynamic, photodynamic, photothermal therapy with guidance by magnetic resonance, photoacoustic, and photothermal imaging. Based on its manifold nanozyme activities (mimicking peroxidase, catalase, superoxide dismutase, glutathione oxidase) and photodynamic property, cascaded nanocatalytic reactions are enabled and sustained in TME for outstanding therapeutic outcomes. The working mechanisms underlying the intraparticulate interactions, sustainability, and self‐replenishment arising from the coupling between the nanocatalytic reactions and nanozyme activities are carefully revealed, providing new insights into the design of novel nanozymes for nanocatalytic therapy with high efficiency, good specificity, and low side effects.