Empowering hydrophobic anticancer drugs by ultrashort peptides: General Co-assembly strategy for improved solubility, targeted efficacy, and clinical application

Feng Gao; Jun Guo; Shihao Liu; Feng Zhang; Yi Zhang; Liping Wang

doi:10.1016/j.jcis.2024.04.013

Empowering hydrophobic anticancer drugs by ultrashort peptides: General Co-assembly strategy for improved solubility, targeted efficacy, and clinical application

J Colloid Interface Sci. 2024 Apr 3:667:119-127. doi: 10.1016/j.jcis.2024.04.013. Online ahead of print.

Authors

Feng Gao¹, Jun Guo², Shihao Liu², Feng Zhang³, Yi Zhang⁴, Liping Wang⁵

Affiliations

¹ Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China; Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
² Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China.
³ Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China; Key Laboratory of Optical Technology and Instrument for Medicine, Ministry of Education, University of Shanghai for Science and Technology, Shanghai 200093, China. Electronic address: fzhang@usst.edu.cn.
⁴ Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. Electronic address: zhangyi@sinap.ac.cn.
⁵ Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China. Electronic address: lpwang-wiucas@ucas.ac.cn.

PMID: 38631250
DOI: 10.1016/j.jcis.2024.04.013

Abstract

The current state of drug delivery systems allows for the resolution of specific issues like inadequate solubility, limited targeting capabilities, and complex preparation processes, requiring tailored designs for different drugs. Yet, the major challenge in clinical application lies in surmounting these obstacles with a universal carrier that is effective for a variety of anticancer drugs. Herein, with the help of computer simulation, we rationally design ultrashort peptides GY and CCYRGD, which can co-assemble with hydrophobic anticancer drugs into nanoparticles with enhanced solubility, targeting ability and anticancer efficacy. Taking 7-ethyl-10-hydroxy camptothecin (SN38) as a model anticancer drug, the co-assembled SN38-GY-CCYRGD nanoparticles significantly enhance the water solubility of SN38 by more than three orders of magnitude. The as-prepared nanoparticles can effectively kill cancer cells, e.g., human small cell lung cancer (A549) cells with a notable cell mortality rate of 71%. Mice experimental results demonstrate the nanoparticles' efficient targeting capability, marked reducing the toxicity to normal tissues while improving antitumor efficacy. This work presents a novel drug delivery method, integrating effective, targeted, and safe strategies into a comprehensive carrier system, designed for the administration of hydrophobic anticancer drugs.

Keywords: Co-assembled nanoparticle; Hydrophobic drug delivery; RGD targeting; Solubility enhancement; Ultrashort peptide.