Matrix Metalloproteinase-2-Responsive Surface-Changeable Liposomes Decorated by Multifunctional Peptides to Overcome the Drug Resistance of Triple-Negative Breast Cancer through Enhanced Targeting and Penetrability

• DOI: 10.1021/acsbiomaterials.2c00295
• Publication Date: 2022-06-06T19:50:28Z
• Authors: Changliang Liu; Zijian Zhao; Rui Gao; Xueying Zhang; Yalan Sun; Jiahui Wu; Jin Liu; Chan Chen
• Keywords: Triple-negative breast cancer; Matrix metalloproteinase inhibitor; Matrix (chemical analysis); Targeted drug delivery

Although nanomedicine has demonstrated great potential for combating drug resistance, its suboptimal recognition of malignant cells and limited transport across multiple biological obstacles seriously impede the efficacious accumulation drugs in tumor lesions, which strikingly limits application clinical therapy drug-resistant triple-negative breast cancer (TNBC). Hence, a surface-variable delivery vehicle based on modification liposomes with multifunctional peptide (named EMC) was fabricated this work used encapsulating doxorubicin p-glycoprotein inhibitor tariquidar. This EMC contains an EGFR-targeting bullet that screened from "one-bead one-compound" combinatorial library, MMP-2-cleaved substrate, cell-penetrating segment. The sequence been validated to possess excellent specificity affinity EGFR at both cellular molecular levels could be unloaded by MMP-2 microenvironment. doxorubicin/tariquidar-coloaded peptide-functionalized liposome (DT-pLip) exhibited superior efficacy growth inhibition TNBC vitro vivo through targeting, osmotic enhancement response MMP-2, controllable release, inhibited efflux. Consequently, our systematic studies indicated liposome-based nanoplatform targeting effects microenvironment-triggered penetration enhancement.