Nanozyme‐based tumor catalytic therapy has attracted widespread attention in recent years, but its therapeutic outcome is drastically diminished by species of nanozyme, concentration of substrate, pH value, and reaction temperature, etc. Herein, a novel Cu‐doped polypyrrole nanozyme (CuP) with trienzyme‐like activities, including catalase (CAT), glutathione peroxidase (GPx), and peroxidase (POD), is first proposed by a straightforward one‐step procedure, which can specifically promote O₂ and ·OH elevation but glutathione (GSH) reduction in tumor microenvironment (TME), causing irreversible oxidative stress damage to tumor cells and reversing the redox balance. The PEGylated CuP nanozyme (CuPP) has been demonstrated to efficiently reverse immunosuppressive TME by overcoming tumor hypoxia and re‐educating macrophage from pro‐tumoral M2 to anti‐tumoral M1 phenotype. More importantly, CuPP exhibits hyperthermia‐enhanced enzyme‐mimic catalytic and immunoregulatory activities, which results in intense immune responses and almost complete tumor inhibition by further combining with αPD‐L1. This work opens intriguing perspectives not only in enzyme‐catalytic nanomedicine but also in macrophage‐based tumor immunotherapy.

Biomimetic delivery systems (BDSs), inspired by the intricate designs of biological systems, have emerged as a groundbreaking paradigm in nanomedicine, offering unparalleled advantages in therapeutic delivery. These systems, encompassing platforms such as liposomes, protein-based nanoparticles, extracellular vesicles, and polysaccharides, are lauded for their targeted delivery, minimized side effects, and enhanced therapeutic outcomes. However, the translation of BDSs from research settings to clinical applications is fraught with challenges, including reproducibility concerns, physiological stability, and rigorous efficacy and safety evaluations. Furthermore, the innovative nature of BDSs demands the reevaluation and evolution of existing regulatory and ethical frameworks. This review provides an overview of BDSs and delves into the multifaceted translational challenges and present emerging solutions, underscored by real-world case studies. Emphasizing the potential of BDSs to redefine healthcare, we advocate for sustained interdisciplinary collaboration and research. As our understanding of biological systems deepens, the future of BDSs in clinical translation appears promising, with a focus on personalized medicine and refined patient-specific delivery systems.

The imbalance between oxidants and antioxidants in cancer cells would evoke oxidative stress-induced cell death, which has been demonstrated to be highly effective in treating malignant tumors. Sonodynamic therapy (SDT) adopts ultrasound (US) as the excitation source to induce the production of reactive oxygen species (ROS), which emerges as a noninvasive therapeutic strategy with deep tissue penetration depth and high clinical safety. Herein, we construct novel sonoactivated oxidative stress amplification nanoplatforms by coating MnO₂ on Au nanoparticle-anchored black phosphorus nanosheets and decorating soybean phospholipid subsequently (Au/BP@MS). The Au/BP@MS exhibit increased ROS generation efficiency under US irradiation in tumor tissues due to Au/BP nanosensitizer-induced improvement of electron-hole separation as well as MnO₂-mediated O₂ generation and GSH depletion, thus leading to notable inhibition effect on tumor growth. Moreover, tumor microenvironment-responsive biodegradability of Au/BP@MS endows them with enhanced magnetic resonance imaging guidance and clinical potential for cancer theranostics.