AUTHOR=Tian Libing , Pei Rui , Zhang Xiaojun , Li Kun , Zhong Yuting , Luo Yougen , Zhou Shu-Feng , Chen Lichan 

TITLE=Tumor Cell-Specific and Lipase-Responsive Delivery of Hydrogen Sulfide for Sensitizing Chemotherapy of Pancreatic Cancer

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.934151

DOI=10.3389/fbioe.2022.934151

ISSN=2296-4185

ABSTRACT=<p>The inability of small molecule drugs to diffuse into tumor interstitium is responsible for the relatively low effectiveness of chemotherapy. Herein, a hydrogen sulfide (H<sub>2</sub>S) gas–involved chemosensitization strategy is proposed for pancreatic cancer treatment by developing a tumor-specific lipase-responsive nanomedicine based on aptamer-conjugated DATS/Dox co-loaded PCL-<italic>b</italic>-PEO micelle (DA/D@Ms-A). After receptor-mediated endocytosis and subsequent digestion of PCL blocks by intracellular lipase, the nanomedicine releases Dox and DATS, which then react with intracellular glutathione to produce H<sub>2</sub>S. The cytotoxicity result indicates that H<sub>2</sub>S can enhance Dox chemotherapy efficiency owing to the synergetic therapeutic effect of Dox and H<sub>2</sub>S. Moreover, the nanomedicine is featured with well tumor penetration capability benefitting from the targeting ability of aptamers and high <italic>in vivo</italic> biocompatibility due to the high density of PEO and biodegradable PCL. The nanomedicine capable of synergetic gas-chemotherapy holds great potential for pancreatic cancer treatment.</p>