Yanzhong Hao,Yaqiao Li,Lu Li,Wenfeng Zang,Zhenzhen Zhao,Zhonggui He,Bingjun Sun
Doxorubicin (DOX), a widely used chemotherapy, suffers from severe cardiotoxicity. Doxil, the first FDA-approved antitumor nanoformulation, mitigates the cardiotoxicity of DOX, but fails to enhance therapeutic efficacy probably due to limited cellular uptake and restricted drug release. To overcome these challenges, this study developed a novel disulfide-acryloyl-modified DOX prodrug (DSSA) for albumin-targeted drug delivery. DSSA could self-assemble into stable nanoassemblies (DSSA NPs) with a high drug-loading capacity (65.46%). DSSA NPs could covalently bind to endogenous albumin, significantly enhancing pharmacokinetics with a nearly 40-fold increase in the area under the curve (AUC) compared to DOX solution (DOX sol) and achieving over twice the tumor accumulation of DOX sol and Doxil. Additionally, the reduction-responsive disulfide bonds enabled selective drug release in tumor microenvironments, minimizing off-target toxicity. These results demonstrate the potential of disulfide-acryloyl modification as a promising prodrug strategy to enhance tumor targeting and safety in chemotherapeutic delivery.
Photothermal therapy (PTT) has been widely known as a promising therapeutic strategy for cancer treatment in recent decades. However, some organic and inorganic photothermal agents exhibit shortcomings including potential long-term toxicity and lack of biodegradability. Biocompatible extracts from plants and animals provide several alternatives for the reformation of photothermal agents. Bio-inspired products still have inherent problems such as low accumulation in tumors, easy diffusion, and fast elimination. Herein, we aim to develop a biocompatible photothermal agent with tumor enrichment. Enlightened by “parasitized snails”, in situ biosynthesis of photothermal agents and fluorescence imaging-guided PTT are achieved with the assistance of alginate–calcium–genipin (ACG) hydrogel. ACG hydrogel is a mixture of alginate (ALG), calcium (Ca), and genipin (GP). Given that the crosslinking product of GP and protein displays fluorescent/photothermal features, the constructed ACG hydrogel can gradually react with the tumor and then “light up” and “ignite” the tumor under specific light excitation. The ACG hydrogel can be seen as a photothermal parasite, eventually leading to the death of tumor. The photothermal therapeutic effects of ACG hydrogel reacting with tumors are successfully proven in vivo. The naturally derived GP and ALG ensure the biosafety of the ACG hydrogel-based bio-application. This work is another successful practice of nature-inspired methodological strategy for in situ biosynthesis of the photothermal agent.Keywords:alginate;hydrogel;genipin;biosynthesis;photothermal therapy
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