Controllable hydrogen release for gas-assisted chemotherapy and ultrasonic imaging of drug-resistant tumors

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Vol. 421; p. 129917
• Main Authors: Wang, Yeying, Liu, Yang, Zhou, Jing-e, Lin, Lizhou, Jia, Chao, Wang, Jing, Yu, Lei, Wang, Yiting, Yan, Zhiqiang
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2021
• Subjects: Ammonia borane; Controllable hydrogen release; Drug-resistant tumors; Hydrogen-assisted chemotherapy; Ultrasonic imaging; Drug-resistant tumors; Hydrogen-assisted chemotherapy; Ultrasonic imaging; Controllable hydrogen release; Ammonia borane
• ISSN: 1385-8947; 1873-3212
• DOI: 10.1016/j.cej.2021.129917

In the weakly acidic tumor environment and lysosomes in tumor cells, AB/DOX@HMPDA-PEG can sensitively release hydrogen as a contrast agent of US imaging. In addition, the massive hydrogen released in lysosomes would 1) promote nanoparticles to escape from lysosome; 2) promote DOX release; 3) block the mitochondrial respiratory chain and overcome the MDR of tumor cells. [Display omitted] •PEGylated Hollow Mesoporous PDA nanoparticles were prepared for the first time.•AB/DOX@HMPDA-PEG could rapidly release H2 in the weakly acidic tumor environment.•The H2 released would enhance the US imaging of tumor and promote DOX release.•The massive H2 released would promote nanoparticles to escape from lysosome.•The massive H2 released would block the mitochondrial respiratory chain. Gas-assisted therapy and diagnosis of tumors have attracted extensive interest due to their low toxicity and convenience, but are severely limited by the uncontrollable gas release. In this work, we proposed a kind of ammonia borane (AB) and doxorubicin (DOX) co-loaded and PEGylated Hollow Mesoporous Polydopamine (AB/DOX@HMPDA-PEG) nanoparticles for acid-sensitive hydrogen (H2)-assisted ultrasonic (US) imaging and chemotherapy of drug-resistant tumors. The in vitro experiment showed that as a high H2-storage molecule, AB can controllably release massive H2 in an acidic environment. For one thing, the H2 release in the acidic tumor environment and lysosomes of tumor cells in vivo helped to improve the US imaging performance; for another, it facilitated the lysosomal escape of nanoparticles, DOX release from nanoparticles, and blockage of mitochondrial respiratory chain. Furtherly, the blockage of mitochondrial respiratory chain reduced the production of triphosadenine (ATP), thereby decreasing the expression of heat shock protein 90 (HSP90) and promoting the therapeutic effect of DOX on drug-resistant tumors. Therefore, the nanoparticles provided an effective platform for controllable H2-assisted chemotherapy and US imaging of the drug-resistant tumors.