Tumor-overexpressed enzyme responsive amphiphiles small molecular self-assembly nano-prodrug for the chemo-phototherapy against non-small-cell lung cancer

Peilian Liu; Yong Huang; Chenyue Zhan; Fu Zhang; Chuansen Deng; Yongmei Jia; Tao Wan; Sheng Wang; Bowen Li

doi:10.1016/j.mtbio.2023.100722

Tumor-overexpressed enzyme responsive amphiphiles small molecular self-assembly nano-prodrug for the chemo-phototherapy against non-small-cell lung cancer

Mater Today Bio. 2023 Jul 4:21:100722. doi: 10.1016/j.mtbio.2023.100722. eCollection 2023 Aug.

Authors

Peilian Liu^{1

2}, Yong Huang², Chenyue Zhan³, Fu Zhang³, Chuansen Deng¹, Yongmei Jia¹, Tao Wan², Sheng Wang¹, Bowen Li^{4

2}

Affiliations

¹ School of Chemistry and Chemical Engineering, Key Laboratory of Clean Energy Materials Chemistry in Guangdong General University, Lingnan Normal University, Zhanjiang, 524048, PR China.
² College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
³ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, 310003, PR China.
⁴ Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, 117585, Singapore.

Abstract

Rational design of self-assembly drug amphiphiles can provide a promising strategy for constructing nano-prodrug with high drug loading, smart stimuli-responsive drug release and high tumor selectivity. Herein, we report a small molecular amphiphile prodrug that can self-assemble into multifunctional nano-prodrug for enhanced anticancer effect by the combination of chemotherapy and phototherapy (PDT/PTT). In this prodrug, the simple insertion of quinone propionate into hydrophilic drug Irinotecan (Ir) generates suitable amphiphiles that endow a good self-assembly behavior of the prodrug and transform it into a stable and uniform nanoparticle. Interestingly, this excellent self-assembly behavior can load phototherapy agent ICG to form a multifunctional nano-prodrug, thereby enhancing the chemotherapeutic effect with PDT/PTT. Importantly, the quinone propionic acid moiety in the prodrug showed a high sensitivity to the overexpressed NAD(P)H:quinone oxidoreductase-1 (NQO1) in non-small cell lung cancer (NSCLC) cells, and this sensitivity enables the disassembly of nano-prodrug and efficient NQO1-responsive drug release. To further enhance the drug accumulation on tumor tissue and migrate the blood clearance, a biomimetic nano-prodrug has been successfully explored by coating hybrid membrane on the above nano-prodrug, which displays high selective inhibition of tumor growth and metastasis on NSCLC mice model. Our findings provide new insights into the rational design of tumor-overexpressed enzyme responsive nano-prodrug for cancer combinational therapy.

Keywords: Amphiphiles small molecular; Combinational therapy; NQO1-Responsive; Nano-prodrug; Self-assembly.