1. Empowering hydrophobic anticancer drugs by ultrashort peptides: General Co-assembly strategy for improved solubility, targeted efficacy, and clinical application.
- Author
-
Gao F, Guo J, Liu S, Zhang F, Zhang Y, and Wang L
- Subjects
- Humans, Animals, Mice, Irinotecan pharmacology, Irinotecan chemistry, A549 Cells, Drug Carriers chemistry, Cell Survival drug effects, Particle Size, Drug Delivery Systems, Drug Screening Assays, Antitumor, Cell Proliferation drug effects, Mice, Inbred BALB C, Surface Properties, Camptothecin chemistry, Camptothecin pharmacology, Camptothecin administration & dosage, Solubility, Hydrophobic and Hydrophilic Interactions, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Nanoparticles chemistry, Peptides chemistry, Peptides pharmacology
- 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF