Co-Delivery of Hesperetin and Cisplatin via Hyaluronic Acid-Modified Liposome for Targeted Inhibition of Aggression and Metastasis of Triple-Negative Breast Cancer

Xiangpeng Wang, Yurong Song, Liuchunyang Yu, Xiaoxia Xue, Mingshi Pang, Yang Li, Xinyi Luo, Zhenglai Hua, Cheng Lu*, Aiping Lu*, Yuanyan Liu*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

9 Citations (Scopus)

Abstract

Having no specific therapy for triple-negative breast cancer (TNBC), this subtype has the lowest survival rate and highest metastatic risk of breast cancer since the tumor inflammatory microenvironment mainly accounts for heterogeneity-induced insensitivity to chemotherapy and epithelial-mesenchymal transition (EMT). This study reports hyaluronic acid (HA)-modified liposomes loaded with cisplatin (CDDP) and hesperetin (Hes) (CDDP-HA-Lip/Hes) for active targeting to relieve systematic toxicity and effective anti-tumor/anti-metastasis ability of TNBC. Our results revealed that HA modification promoted the cellular uptake of the synthesized CDDP-HA-Lip/Hes nanoparticles in MDA-MB-231 cells and accumulation in tumor sites in vivo, indicating deeper tumor penetration. Importantly, CDDP-HA-Lip/Hes inhibited the PI3K/Akt/mTOR pathway to alleviate the inflammation in the tumor and with a crosstalk to suppress the process of the EMT, increasing the chemosensitivity and inhibiting tumor metastasis. Meanwhile, CDDP-HA-Lip/Hes could significantly inhibit the aggression and metastasis of TNBC with less side effects on normal tissues. Overall, this study provides a tumor-targeting drug delivery system with great potential for treating TNBC and its lung metastasis robustly.

Original languageEnglish
Pages (from-to)34360-34377
Number of pages18
JournalACS Applied Materials and Interfaces
Volume15
Issue number29
Early online date11 Jul 2023
DOIs
Publication statusPublished - 26 Jul 2023

Scopus Subject Areas

  • Materials Science(all)

User-Defined Keywords

  • triple-negative breast cancer
  • cisplatin
  • hesperetin
  • hyaluronic acid modified liposomes
  • anti-metastasis
  • tumor targeting

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