Tailor-made biotuner against colorectal tumor microenvironment to transfer harms into treasures for synergistic oncotherapy. (December 2022)

• Record Type: Journal Article
• Authors: Liang, Jun-Long; Niu, Mei-Ting; Luo, Guo-Feng; Zhang, Shi-Man; Huang, Qian-Xiao; Jin, Xiao-Kang; Lu, Zhibing; Chen, Wei-Hai; Zhang, Xian-Zheng
• Is Part Of: Nano today. Volume 47(2022)
• Publication Date: 2022-12
• Subjects: Bacterial metabolism -- Hydrogen sulfide -- Short-chain fatty acids -- Tumor microenvironment -- Metabolic therapy; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2022.101662
• Languages: English
• ISSNs: 1748-0132

Abstract

Abstract: The endogenous tumor-specific metabolites in tumor microenvironment (TME) have emerged as powerful motivators for tumor progression. In situ transformation of these harmful substances into treasures provides an innovative strategy to revolutionize cancer therapy. Herein, a tailor-made Bac@Cu2 O biotuner is ingeniously designed against the specific physiological features of colorectal cancer (CRC) for synergistic oncotherapy. The intelligent biotuner is constructed by the integration of bacteria (i.e., Eubacterium hallii (E. hallii)) and Cu2 O nanoparticles via electrostatic interaction. With the instinctive E. hallii-driven tumor tropism, Bac@Cu2 O could actively accumulate and colonize at the tumor sites. Subsequently, Cu2 O can act as a H2 S scavenger to react with CRC overexpressed H2 S, resulting in the generation of CuS, which could mediate Fenton-like reaction to produce cytotoxic OH for chemodynamic therapy (CDT). Moreover, the colonized E. hallii in TME is able to effectively metabolize detrimental lactic acid into antitumor short-chain fatty acids (SCFAs) for tumor-targeted metabolic therapy. These functions conjunctively produce a "turn-bads-to-goods" scenario for chemodynamic-metabolic synergistic CRC therapy. Such a tailor-made biological material provides a simple and powerful strategy in boosting anti-CRC efficiency without the use of cytotoxic drugs, greatly enhancing the therapeutic outcomes as well as reducing the potential side effects. Graphical Abstract: A "turn-bads-to-goods" scenario for synergistic oncotherapy : The tailor-made Bac@Cu2 O biotuner was is ingeniously designed against the specific physiological features of colorectal tumor. The Bac@Cu2 O biotuner could actively target and colonize at the tumor sites, where the overexpressed lactate and H2 S in the colorectal TME would be consumed by E. hallii and Cu2 O, respectively, thus ameliorating colorectal TME and boosting the therapeutic efficacy. ga1 Highlights: Tailor-made Bac@Cu2 O biotuner could transfer harms into treasures for synergistic colorectal cancer therapy. The biotuner colonized in TME could effectively metabolize detrimental lactate into SCFAs for metabolic therapy. Biotuner could eliminate overexpressed H2 S in CRC, and subsequently mediate Fenton-like reaction for chemodynamic therapy. Biotuner exerts antitumor cascade by combining chemodynamic and metabolic therapy via "turn-bads-to-goods" scenario.