The chemotherapeutic efficacy of hyaluronic acid coated polymeric nanoparticles against breast cancer metastasis in female NCr-Nu/Nu nude mice
Document Type
Article
Publication Date
1-1-2023
Abstract
Polyethylene glycol (PEG) coated Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for cancer treatment are biocompatible, nonimmunogenic and accumulate in tumour sites due to the enhanced permeability and retention (EPR). Doxorubicin (DOX) is a potent but cardiotoxic anticancer agent. Hyaluronic acid (HA) occurs naturally in the extra-cellar matrix and binds to CD44 receptors which are overexpressed in cancer metastasis, proven to be characteristic of cancer stem cells and responsible for multidrug resistance. In this study, an athymic mice model of breast cancer metastasis was developed using red fluorescent protein (RFP)-labelled triple negative cancer cells. The animals were divided into four treatment groups (Control, HA-PEG-PLGA nanoparticles, PEG-PLGA nanoparticles, and Free DOX). The tumour size growth was assessed until day 25 when animals were sacrificed. Mice treated with HA-PEG-PLGA NPs inhibited tumour growth. The tumour growth at day 25 (118% +/- 13.0) was significantly (p < 0.05) less than PEG-PLGA NPs (376% +/- 590 and control (826% +/- 970). Fluorescent microscopy revealed that HA-PEG-PLGA NPs had significantly (p < 0.05) less metastasis in liver, spleen, colon, and lungs as compared to control and to Free DOX groups. The efficacy of HA-PEG-PLGA NPs was proven in vivo. Further pharmacokinetic and toxicity studies are required for this formulation to be ready for clinical research.
Keywords
Hyaluronic acid, PEG-PLGA nanoparticles, Nanoprecipitation, Athymic mice, Doxorubicin
Divisions
fac_med
Funders
Ministry of Higher Education Malaysia Fundamental Research Grant Scheme (FRGS FP031-2014A),Prototype Research Grant Scheme (PRGS PR002-2021)
Publication Title
Polymers
Volume
15
Issue
2
Publisher
MDPI
Publisher Location
ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND