Effectiveness of drug-loaded poly(ethylene glycol) and poly(lactic-co-glycolic-acid) nanoparticles in the in vitro treatment of breast cancer: a systematic review

TL;DR

This review evaluates how well PEG–PLGA nanoparticles deliver cancer drugs to breast cancer cells in lab tests, showing improved drug effectiveness and cell death.

Contribution

The study systematically reviews the in vitro efficacy of PEG–PLGA nanoparticles for breast cancer treatment, highlighting their drug delivery advantages.

Findings

PEG–PLGA nanoparticles significantly reduced breast cancer cell viability and increased apoptosis compared to free drugs.

Functionalization with ligands like folic acid improved drug targeting and cytotoxicity in breast cancer cells.

Molecular analyses showed upregulation of p53, Bax, and caspases, and downregulation of Bcl-2 and hTERT genes.

Abstract

Breast cancer treatment remains a major challenge to modern medicine and has driven the need for nanotechnology-based strategies to improve drug delivery and overcome chemoresistance. Poly(ethylene glycol) and poly (lactic-co-glycolic acid) (PEG–PLGA) nanoparticles (NPs) are a type of FDA-approved biodegradable copolymer (lactic + glycolic acids) that degrades into non-toxic metabolites (lactic acid and glycolic acid); it has emerged as a promising drug carrier owing to its biocompatibility, sustained release properties, and ability to enhance the cellular uptake of chemotherapeutic agents. This systematic review examines the efficacies of PEG–PLGA nanoparticles loaded with antineoplastic drugs on in vitro models of breast cancer cell lines.

Following PRISMA guidelines, we conducted a comprehensive search of the Web of Science, Embase, MEDLINE, and Scopus databases to identify experimental studies published between 2014 and August 2025 that evaluated PEG–PLGA formulations applied to breast cancer cell lines. The methodological quality of each study was appraised using the National Institute for Health and Care Excellence (NICE) criteria.

Thirteen studies were chosen based on our inclusion criteria. Here, the PEG–PLGA nanoparticles were predominantly spherical (30–210 nm) and exhibited controlled release kinetics. Compared with free drugs, the nanoformulations significantly reduced cell viability, increased apoptosis, and induced cell-cycle arrest. Functionalization with ligands such as folic acid enhanced drug targeting and cytotoxicity, while the molecular analyses revealed upregulation of p53, Bax, and caspases as well as downregulation of Bcl-2 and hTERT genes.

PEG–PLGA nanoparticles can substantially improve the selectivity, bioavailability, and cytotoxic efficacies of anticancer drugs in breast cancer in vitro. These findings underscore their translational potential as next-generation drug-delivery systems, warranting in vivo validation as well as development of theranostic- and stimulus-responsive designs for personalized oncology.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251076570.

PEG-PLGA nanoparticles are used in cell line in vitro assays such as MTT, flow cytometry, and qPCR for targeted breast cancer therapy. Key outcomes include increased cytotoxicity, apoptosis, and Bcl-2; p53 remains unchanged.

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