In Situ Constructed Nano‐Drug Depots through Intracellular Hydrolytic Condensation for Chemotherapy of Bladder Cancer

• Published in: Angewandte Chemie International Edition 2022-04, Vol.61 (18), p.e202116893-n/a
• Main Authors: Hou, Da‐Yong, Zhang, Ni‐Yuan, Wang, Man‐Di, Xu, Shao‐Xin, Wang, Zhi‐Jia, Hu, Xing‐Jie, Lv, Gan‐Tian, Wang, Jia‐Qi, Wu, Xiu‐Hai, Wang, Lu, Cheng, Dong‐Bing, Wang, Hao, Xu, Wanhai
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antitumor activity; Bladder; Bladder Cancer; Cancer; Cancer therapies; Cell Line, Tumor; Chemotherapy; Doxorubicin; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug Carriers - therapeutic use; Drug Delivery Systems - methods; Drug development; Drugs; Female; Humans; Intracellular; Male; Mice; Nano-Drug Depots; Nanoparticles; Nanoparticles - therapeutic use; Retention time; Self-Assembly; Silanes; Sustained Release; Tumor cells; Tumors; Urinary Bladder Neoplasms - drug therapy
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202116893

Intravesical administration of first‐line drugs has shown failure in the treatment of bladder cancer owing to the poor tumor retention time of chemotherapeutics. Herein, we report an intracellular hydrolytic condensation (IHC) system to construct long‐term retentive nano‐drug depots in situ, wherein sustained drug release results in highly efficient suppression of bladder cancer. Briefly, the designed doxorubicin (Dox)‐silane conjugates self‐assemble into silane‐based prodrug nanoparticles, which condense into silicon particle‐based nano‐drug depots inside tumor cells. Significantly, we demonstrate that the IHC system possesses highly potent antitumor efficacy, which leads to the regression and eradication of large established tumors and simultaneously extends the overall survival of air pouch bladder cancer mice compared with that of mice treated with Dox. The concept of intracellular hydrolytic condensation can be extended via conjugating other chemotherapeutic drugs, which may facilitate rational design of novel nanomedicines for augmentation of chemotherapy. An intracellular hydrolytic condensation (IHC) system to construct long‐term retentive nano‐drug depots in situ is presented. Based on silicon particles, the nano‐drug depots are capable of sustained drug release, which results in highly efficient suppression of bladder cancer.