PEGylated PLGA Nanoformulations For Effective Immunomodulatory Actors In Non-Small Cell Lung Cancer - Review

Sep 22, 2026

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PEGylated poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles are described as a versatile, biocompatible nanoplatform for non-small cell lung cancer (NSCLC) therapy. Their prolonged circulation, controllable drug release, and modifiable surfaces support improved tumor accumulation with reduced systemic toxicity. The review covers progress in delivery of chemotherapeutics, active targeting via ligand conjugation, and modulation of the tumor immune microenvironment, including antigen presentation, reduced immunosuppression, and synergy with immune checkpoint blockade. Key barriers to clinical translation include scalable manufacturing, reproducibility, and regulatory issues, alongside future outlooks for targeted immune-based treatments.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Introduction

Non-small cell lung cancer challenges

Immunosuppressive tumor microenvironment barriers

International Journal of Nanomedicine Open Access Full Text Article REVIEW PEGylated PLGA Nanoformulations For Effective Immunomodulatory Actors In Non–Small Cell Lung Cancer Mingyao Huang 1 , *, Jiahui Zhang2 , *, Zhanying Hao 3 , Qian Wang4 , Wei Liu 5 1School of Basic Medicine Science, Key Laboratory of Translational Tumor Medicine in Fujian Province, Putian University, Putian, Fujian, 351100, People’s Republic of China; 2China Medical University, Shenyang, 110000, People’s Republic of China; 3Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People’s Republic of China; 4Department of Anesthesiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People’s Republic of China; 5Department of 2nd Emergency, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People’s Republic of China *These authors contributed equally to this work Correspondence: Wei Liu; Qian Wang, Email [il_lsl_phd@163.com](il_lsl_phd@163.com); [1878879828@qq.com](1878879828@qq.com) | Abstract: PEGylated poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles have attracted increasing attention as a versatile and biocompatible nanoplatform for non-small cell lung cancer (NSCLC) therapy. Benefiting from prolonged circulation time, controllable drug-release behavior, and flexible surface modification, PEG-PLGA nanocarriers can effectively enhance tumor accumulation while reducing systemic toxicity. Recent advances indicate that PEG-PLGA nanoparticles not only improve the delivery efficiency of chemotherapeutic agents but also enable active tumor targeting through ligand conjugation and contribute to the regulation of the tumor immune microenvironment. In particular, these nanoplatforms have shown promising potential in enhancing antigen presentation, alleviating immunosuppression, and synergizing with immunotherapeutic strategies such as immune checkpoint blockade. Nevertheless, several challenges remain for clinical translation, including large-scale manufacturing, formulation reproducibility, and regulatory considerations. Overall, this review highlights the current progress, remaining challenges, and future perspectives of PEG-PLGA nanoparticles for targeted and immune-based therapies in NSCLC.
Keywords: PEG-PLGA nanoparticles, non-small cell lung cancer, drug delivery, immunotherapy, nanomedicine | | --- | | Introduction
Non-small cell lung cancer (NSCLC) is the most prevalent subtype of lung cancer, accounting for over 85% of cases globally.1,2 Despite advances in surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, treatment outcomes remain suboptimal due to a combination of systemic toxicity, drug resistance, and insufficient tumor selectivity.3–6 Conventional anticancer agents often lack specificity, harming both cancerous and healthy cells, which results in severe side effects and limits the tolerated dosage.7,8 Compounding this issue, tumor cells frequently acquire resistance through mechanisms such as enhanced drug efflux, mutations in target proteins, or pathway redundancy, which contributes to therapeutic failure and disease recurrence.9–12
The immunosuppressive tumor microenvironment (TME) further complicates NSCLC therapy.13 Tumor heterogeneity, comprising diverse cellular and genetic subpopulations within the same lesion, restricts homogeneous drug distribution and diminishes the efficacy of both chemotherapeutic and immune-based agents.14–16 Physical barriers such as elevated interstitial fluid pressure and dense extracellular matrix structures in solid tumors impede drug penetration and limit immune cell infiltration.17, 18 Additionally, many immunotherapeutics, including cytokines, antibodies, and nucleic acids, suffer from poor aqueous solubility and metabolic instability, which severely reduces their bioavailability and therapeutic performance.19–21 These limitations highlight th

FAQs

What advantages do PEG-PLGA nanoparticles offer for NSCLC therapy?

They provide prolonged circulation, controllable drug release, and flexible surface modification, improving tumor accumulation while reducing systemic toxicity.

How do PEG-PLGA nanocarriers influence the tumor immune microenvironment?

They can enhance antigen presentation, alleviate immunosuppression, and support active targeting through ligand conjugation, which helps synergize with immunotherapies such as immune checkpoint blockade.

What challenges still hinder clinical translation of PEG-PLGA formulations?

The review highlights difficulties with large-scale manufacturing, formulation reproducibility, and regulatory considerations.

Sep 22, 2026

Upload by dhado