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 language | English |
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Pages (from-to) | 34360-34377 |
Number of pages | 18 |
Journal | ACS Applied Materials and Interfaces |
Volume | 15 |
Issue number | 29 |
Early online date | 11 Jul 2023 |
DOIs | |
Publication status | Published - 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