Search

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]

Antibacterial photocatalytic therapy (APCT) is one of the most promising non‐antibiotic treatment strategies for biofilm‐infected wounds and inflammation caused by drug‐resistant bacteria. However, it still faces issues such as inadequate single antibacterial capacity and lack of antioxidant capacity. In this study, a Z‐scheme heterojunction (Bi2S3‐X@PDA) is designed using a polydopamine (PDA) shell firmly anchored to the surface of sulfur vacancy‐rich bismuth sulfide nanorods (Bi2S3‐X NRs). Under near‐infrared light and hydrogen peroxide, Bi2S3‐X@PDA significantly improves the photocatalytic efficiency of reactive oxygen species generation and shows a nearly 100% broad‐spectrum antibacterial effect against multiple bacterial strains and bacterial biofilms in vitro. Interestingly, the antioxidant activity of the PDA shell in Bi2S3‐X@PDA remarkably downregulates the expression of pro‐inflammatory factors and promotes macrophage reprogramming toward the proregenerative M2 phenotype. In a mouse wound model of methicillin‐resistant Staphylococcus aureus biofilm infection, Bi2S3‐X@PDA effectively eliminates drug‐resistant bacterial biofilms through APCT/mild photothermal therapy, while reducing inflammation in normal tissues and regulating the immune microenvironment, thereby promoting rapid wound healing. Overall, this light‐controlled treatment strategy, which provides both antibacterial and anti‐inflammatory functions, is a reliable tool for combating biofilm infection and inflammation caused by drug‐resistant bacteria. [ABSTRACT FROM AUTHOR]

Synergistic photothermal immunotherapy has emerged as a favorable therapeutic approach to fight cancer. However, design of an effective photothermal immunotherapy system to suppress tumor growth and simultaneously inhibit tumor metastases continues to be a challenge. Here a dual toll‐like receptor agonists delivery system CPG@Au NRs/m‐R848 for combined photothermal immunotherapy of melanoma is developed. CPG@Au NRs/m‐R848 displays strong antitumor effects by promoting maturation of dendritic cells (DCs) and reprogramming of M2 macrophages into M1 phenotype. Moreover, immunogenic cell death (ICD) induced by photothermal ablation of Au NRs could synergistically produce in situ vaccination effect with CPG ODN and R848, generating systemic and lasting antitumor immunity. It is further proved that CPG@Au NRs/m‐R848 treatment inhibits tumor growth in bilateral B16F10 tumors model by eliciting CD8+ T cell response. Overall, this work suggests that this strategy hold great potential in tumor immunotherapy by regulating tumor‐associated macrophage polarization, triggering DCs maturation and inducing ICD. [ABSTRACT FROM AUTHOR]

Metastatic osteosarcoma usually has an unsatisfactory response to the current standard chemotherapy and causes poor prognosis. Currently, epithelial-mesenchymal transition (EMT) is reported as a critical event in osteosarcoma metastasis. Glaucocalyxin A, a bioactive ent-kauranoid diterpenoid, exerts anti-cancer effect on osteosarcoma by inducing apoptosis in previous study. However, the effect of Glaucocalyxin A on EMT and metastasis of osteosarcoma is unclear. In this study, we investigated the potential mechanisms of Glaucocalyxin A on EMT and metastasis of osteosarcoma. We found that Glaucocalyxin A inhibited migration and invasion of MG-63 and 143B cells. Moreover, Glaucocalyxin A increased the protein and mRNA levels of E-cadherin and decreased the protein and transcription expression of N-cadherin, Vimentin. Glaucocalyxin A also inhibited the protein and mRNA levels of EMT-associated transcription factor including Snail and Slug. Furthermore, Glaucocalyxin A inhibited transforming growth factor-β1 (TGF-β1)-induced migration, invasion and EMT of low-metastatic osteosarcoma U2OS cells. Glaucocalyxin A inhibited TGF-β-induced phosphorylation of Smad 2/3 in osteosarcoma U2OS cells. Finally, we established transplanted metastatic models of highly metastatic osteosarcoma 143B cells. Glaucocalyxin A inhibited lung metastasis in vivo. Interestingly, Glaucocalyxin A increased the protein expression of E-cadherin and reduced the protein expression of N-cadherin and Vimentin. Glaucocalyxin A inhibited the protein expression of Snail and Slug in vivo. In summary, this study demonstrated that Glaucocalyxin A inhibited EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma. Therefore, Glaucocalyxin A might be a promising candidate against the metastasis of human osteosarcoma. • Glaucocalyxin A reverses epithelial-mesenchymal transition (EMT) in osteosarcoma. • Glaucocalyxin A prevents TGF-β1-induced EMT by inhibiting Smad2/3 pathway in osteosarcoma. • Glaucocalyxin A inhibits osteosarcoma metastasis to lung in the metastatic model. [ABSTRACT FROM AUTHOR]