A tumor targeted nano micelle carrying astragaloside IV for combination treatment of bladder cancer

• Published in: Scientific reports 2024-07, Vol.14 (1), p.17704-14, Article 17704
• Main Authors: Kong, Chenfan, Sun, Jianrong, Hu, Xinzi, Li, Guangzhi, Wu, Song
• Format: Article
• Language: English
• Subjects: 631/67; 639/301; 692/4025; Animals; aPD-L1; Astragaloside IV; Bladder cancer; Cell Line, Tumor; Combination therapy; Drug delivery; Drug Delivery Systems; Female; Herbal medicine; Humanities and Social Sciences; Humans; Hydrophobicity; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - pharmacology; Immunotherapy; Lymphocytes T; Mice; Micelles; Microenvironments; multidisciplinary; Nanomedicine; Nanoparticles - chemistry; NF-κB protein; Retention time; Saponins - administration & dosage; Saponins - chemistry; Saponins - pharmacology; Science; Science (multidisciplinary); Stat3 protein; Triterpenes - administration & dosage; Triterpenes - chemistry; Triterpenes - pharmacology; Tumor cells; Tumor targeted micelles; Tumor-infiltrating lymphocytes; Tumors; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Xenograft Model Antitumor Assays; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-66010-3

Immune checkpoint inhibitors (ICIs) are effective agents for tumor immunotherapy. However, their clinical effectiveness is unsatisfactory due to off-target effects and a suppressive immune microenvironment. This study developed a nanodrug delivery system for bladder cancer (BCa) using PCL-MPEG and PCL-PEG-CHO to synthesize internal hydrophobic and external hydrophilic micelles (PP) that encapsulated water-insoluble astragaloside IV (PPA). The aldehyde group on the surface of PPA reacted with the amino group of aPD-L1, allowing the decoration of this antibody on the surface of the micelles. The resultingPPA@aPD-L1effectively piggybacked astragaloside IV and aPD-L1 antibody. These findings suggest that PPA@aPD-L1 is relatively stable in circulation and efficiently binds to BCa cells with the aid of aPD-L1. Additionally, this strategy prolongs the drug’s retention time in tumors. Compared to PBS, PP, and PPA with PPA + aPD-L1 groups, PPA@aPD-L1significantly prolonged the survival of mice with BCa and reduced tumor volume. Mechanistic studies showed that PPA inhibited the NF-κB and STAT3 signaling pathways in tumor cells. Additionally, PPA@aPD-L1increased IFN-γ and decreased IL-10 expression in bladder tumors, affecting the number and type of intratumorally infiltrating T cells. Our study presents a simple and effective drug delivery system that combines herbal monomers with ICIs. It has demonstrated a potent ability to suppress tumor growth and holds potential for future applications.