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Cancer is a significant global health challenge, and while chemotherapy remains a widely used treatment, its non-specific toxicity and broad distribution can lead to systemic side effects and limit its effectiveness against tumors. Therefore, the development of safer chemotherapy alternatives is crucial. Prodrugs hold great promise, as they remain inactive until they reach the cancer site, where they are selectively activated by enzymes or specific factors, thereby reducing side effects and improving targeting. However, subtle differences in the microenvironments between tumors and normal tissue may still result in unintended cytotoxicity. Bioorthogonal reactions, known for their selectivity and precision without interfering with natural biochemical processes, are gaining attention. When combined with prodrug strategies, these reactions offer the potential to create highly effective chemotherapy drugs. This review examines the safety and efficacy of prodrug strategies utilizing various bioorthogonal reactions in cancer treatment. [ABSTRACT FROM AUTHOR]

The article presents the discussion on development of cyto-adhesive micropatches (CAMPs) designed to activate neutrophils for tumor immunotherapy, offering a new approach to adoptive neutrophil therapy in solid tumors. Topics include neutrophil roles in tumor progression, the differentiation between pro-tumor N2 and anti-tumor N1 phenotypes; and the potential of activated neutrophils to enhance antitumor immunity.

Camptothecin (CPT) is a highly cytotoxic molecule with excellent antitumor activity against various cancers. However, its clinical application is severely limited by poor water solubility, easy inactivation, and severe toxicity. Structural modifications and nanoformulations represent two crucial avenues for camptothecin's development. However, the potential for further structural modifications is limited, and camptothecin nanoparticles fabricated via physical loading have the drawbacks of low drug loading and leakage. Prodrug‐based CPT nanoformulations have shown unique advantages, including increased drug loading, reduced burst release, improved bioavailability, and minimal toxic side effects. Stimulus‐responsive CPT nano‐prodrugs that respond to various endogenous or exogenous stimuli by introducing various activatable linkers to achieve spatiotemporally responsive drug release at the tumor site. This review comprehensively summarizes the latest research advances in stimulus‐responsive CPT nano‐prodrugs, including preparation strategies, responsive release mechanisms, and their applications in cancer therapy. Special focus is placed on the release mechanisms and characteristics of various stimulus‐responsive CPT nano‐prodrugs and their application in cancer treatment. Furthermore, clinical applications of CPT prodrugs are discussed. Finally, challenges and future research directions for CPT nano‐prodrugs are discussed. This review to be valuable to readers engaged in prodrug research is expected. [ABSTRACT FROM AUTHOR]

Inflammation‐associated diseases are very common clinically with a high incidence; however, there is still a lack of effective treatments. Cell‐biomimetic nanoplatforms have led to many breakthroughs in the field of biomedicine, significantly improving the efficiency of drug delivery and its therapeutic implications especially for inflammation‐associated diseases. Macrophages are an important component of immune cells and play a critical role in the occurrence and progression of inflammation‐associated diseases while simultaneously maintaining homeostasis and modulating immune responses. Therefore, macrophage‐biomimetic nanoplatforms not only inherit the functions of macrophages including the inflammation tropism effect for targeted delivery of drugs and the neutralization effect of pro‐inflammatory cytokines and toxins via membrane surface receptors or proteins, but also maintain the functions of the inner nanoparticles. Macrophage‐biomimetic nanoplatforms are shown to have remarkable therapeutic efficacy and excellent application potential in inflammation‐associated diseases. In this review, inflammation‐associated diseases, the physiological functions of macrophages, and the classification and construction of macrophage‐biomimetic nanoplatforms are first introduced. Next, the latest applications of different macrophage‐biomimetic nanoplatforms for the treatment of inflammation‐associated diseases are summarized. Finally, challenges and opportunities for future biomedical applications are discussed. It is hoped that the review will provide new ideas for the further development of macrophage‐biomimetic nanoplatforms. [ABSTRACT FROM AUTHOR]

Bone defects in osteoporosis usually present excessive reactive oxygen species (ROS), abnormal inflammation levels, irregular shapes and impaired bone regeneration ability; therefore, osteoporotic bone defects are difficult to repair. In this study, an injectable thermosensitive hydrogel poly (D, L‐lactide)‐poly (ethylene glycol)‐ poly (D, L‐lactide) (PLEL) system containing resveratrol (Res) and dexamethasone (DEX) is designed to create a microenvironment conducive to osteogenesis in osteoporotic bone defects. This PLEL hydrogel is injected and filled irregular defect areas and achieving a rapid sol‐gel transition in situ. Res has a strong anti‐inflammatory effects that can effectively remove excess free radicals at the damaged site, guide macrophage polarization to the M2 phenotype, and regulate immune responses. Additionally, DEX can promote osteogenic differentiation. In vitro experiments showed that the hydrogel effectively promoted osteogenic differentiation of mesenchymal stem cells, removed excess intracellular ROS, and regulated macrophage polarization to reduce inflammatory responses. In vivo experiments showed that the hydrogel promoted osteoporotic bone defect regeneration and modulated immune responses. Overall, this study confirmed that the hydrogel can treat osteoporotic bone defects by synergistically modulating bone damage microenvironment, alleviating inflammatory responses, and promoting osteogenesis; thus, it represents a promising drug delivery strategy to repair osteoporotic bone defects. [ABSTRACT FROM AUTHOR]