Journal Article

Tumor Microenvironment Responsive Key Nanomicelles for Effective Against Invasion and Metastasis in Ovarian Cancer Using Mice Model

Li, Xue-Tao, Yu, Yang, Zang, Juan, Zhang, Lu, Chen, You-Qiang, Cheng, Lan, Li, Shu-Tong, Liu, Yang, Kong, Liang, Guo, Rui-Bo

2025

Overview

Ovarian cancer is difficult to detect in its early stages, and it has a high potential for invasion and metastasis, along with a high rate of recurrence. These factors contribute to the poor prognosis and reduced survival times for patients with this disease. The effectiveness of conventional chemoradiotherapy remains limited. Nano-particles, as a novel drug delivery system, have significant potential for improving therapeutic efficacy and overcoming these challenges. According to the high expression level of matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment, MMP-2 responsive nano-particles (PVGLIG-MTX-D/T-NMs) containing docetaxel and triptolide were prepared by the thin-film dispersion method. The synergistic effect between docetaxel and triptolide was systematically investigated, the ratio of the two drugs was optimized, and the physicochemical properties of the nano-particles and their ability to inhibit ovarian cancer cell growth and metastasis were evaluated in vitro and in vivo. PVGLIG-MTX-D/T-NMs enhanced the targeting, stability, and bioavailability of the drug, while reducing the dose and toxicity. In addition, by regulating the expression levels of E-Cadherin, N-Cadherin, matrix metalloproteinases (MMPs), hypoxia-inducible factor 1-alpha (HIF-1α), and vascular endothelial growth factor (VEGF), it exhibited an inhibitory effect on epithelial-mesenchymal transformation (EMT) and tumor cell angiogenesis, and effectively inhibited the invasion and metastasis of ovarian cancer cells. PVGLIG-MTX-D/T-NMs achieved passive targeting of tumor sites by enhancing permeability and retention (EPR) effects. Subsequently, the uptake of the drug by tumor cells was enhanced by MMP-2 responsiveness and the modification of methotrexate targeting ligands. By regulating the expression levels of invasion- and metastasis-related proteins in tumor tissues, the nano-particles affected the EMT process, inhibited tumor angiogenesis, and suppressed the malignant potential of invasion and metastasis in ovarian cancer. These findings provided a new direction for further exploration of tumor-targeted therapy.

• Publisher: Dove,Dove Medical Press
• Subject: angiogenesis / Animals / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacokinetics / Antineoplastic Agents - pharmacology / Cell Line, Tumor / Diterpenes / docetaxel / Docetaxel - administration & dosage / Docetaxel - chemistry / Docetaxel - pharmacokinetics / Docetaxel - pharmacology / Drug Delivery Systems / epithelial mesenchymal transition / Epoxy Compounds / Female / Humans / Matrix Metalloproteinase 2 - metabolism / Mice / Mice, Inbred BALB C / Mice, Nude / Micelles / nano-drug delivery system / Nanoparticles - administration & dosage / Nanoparticles - chemistry / Neoplasm Invasiveness - prevention & control / Neoplasm Metastasis / Original Research / Ovarian Neoplasms - drug therapy / Ovarian Neoplasms - metabolism / Ovarian Neoplasms - pathology / Phenanthrenes - administration & dosage / Phenanthrenes - chemistry / Phenanthrenes - pharmacokinetics / Phenanthrenes - pharmacology / triptolide / tumor microenvironment / Tumor Microenvironment - drug effects / Xenograft Model Antitumor Assays