---
title: "EGFR-targeted PLGA nanoparticles co-delivering nivolumab and galunisertib for NSCLC therapy"
id: "pubmed-42648563"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42648563"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42648563/"
doi: "10.1016/j.ijpharm.2026.127338"
published_at: "2026-10-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# EGFR-targeted PLGA nanoparticles co-delivering nivolumab and galunisertib for NSCLC therapy
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42648563
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42648563/)
- **DOI:** [10.1016/j.ijpharm.2026.127338](https://doi.org/10.1016%2Fj.ijpharm.2026.127338)
- **Published At:** 2026-10-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This study developed an EGFR-targeted spherical polymeric nanoparticle system co-encapsulating **nivolumab** (a PD-1 inhibitor) and **galunisertib** (a TGF-β inhibitor) to enhance immunotherapeutic efficacy against **non-small cell lung cancer** (NSCLC). - Nanoparticles were composed of PLGA derivatives and conjugated with an anti-EGFR antibody for targeted delivery to tumor tissue. - In vitro characterization included measurements of particle size, zeta potential, morphology, drug release, cytotoxicity in healthy and tumor cell lines, and assessment of T cell immune responses; results were reported as promising in the source. - In vivo testing used humanized mice bearing heterotopic xenograft tumors to evaluate biodistribution, antitumor efficacy, and tolerability. - Biodistribution studies showed that antibody-conjugated nanoparticles achieved higher tumor accumulation than control (non-targeted) formulations. - Targeted, co-loaded nanoparticles provided antitumor activity comparable to the free-drug combination while enabling **tumor-directed delivery** and demonstrating a more favorable preliminary tolerability profile in the animal model. - The authors highlight that combining a checkpoint inhibitor with a TGF-β pathway inhibitor within a targeted nanoparticle may address limitations of current immunotherapies, such as limited efficacy and off-target effects. - Keywords and focus areas reported include **Drug delivery**, **Galunisertib**, **Immunotherapy**, **NSCLC**, **Nivolumab**, **PLGA**, and **Polymeric nanoparticles**. - The publication discloses funding support from The Scientific and Technological Research Council of Turkey (TUBITAK) and the Hacettepe University Scientific Research Projects Coordination Unit; competing interests are declared by the authors.
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Epub 2026 Aug 26. # Codelivery of nivolumab and galunisertib by EGFR-targeted spherical polymeric nanoparticles for effective treatment of non-small cell lung cancer [Meryem Kaplan](https://pubmed.ncbi.nlm.nih.gov/?term=Kaplan+M&cauthor_id=42648563)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#full-view-affiliation-1 "Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey; Department of Pharmaceutical Technology, Faculty of Pharmacy, Süleyman Demirel University, 32260 Isparta, Turkey."), [Ece Tavukçuoğlu](https://pubmed.ncbi.nlm.nih.gov/?term=Tavuk%C3%A7uo%C4%9Flu+E&cauthor_id=42648563)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#full-view-affiliation-2 "Department of Basic Oncology, Hacettepe University Cancer Institute, 06100 Ankara, Turkey."), [Süleyman Can Öztürk](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%96zt%C3%BCrk+SC&cauthor_id=42648563)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#full-view-affiliation-3 "Centre for Laboratory Animals Research and Application, Hacettepe University Ankara, Turkey; Department of Vaccine Technology, Vaccine Institute, Hacettepe University Ankara, Turkey."), [Sema Çalış](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%87al%C4%B1%C5%9F+S&cauthor_id=42648563)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#full-view-affiliation-4 "Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey."), [Güneş Esendağlı](https://pubmed.ncbi.nlm.nih.gov/?term=Esenda%C4%9Fl%C4%B1+G&cauthor_id=42648563)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#full-view-affiliation-2 "Department of Basic Oncology, Hacettepe University Cancer Institute, 06100 Ankara, Turkey."), [Kivilcim Ozturk](https://pubmed.ncbi.nlm.nih.gov/?term=Ozturk+K&cauthor_id=42648563)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#full-view-affiliation-5 "Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. Electronic address: k.ozturk@hacettepe.edu.tr.") Affiliations Expand ### Affiliations * 1 Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey; Department of Pharmaceutical Technology, Faculty of Pharmacy, Süleyman Demirel University, 32260 Isparta, Turkey. * 2 Department of Basic Oncology, Hacettepe University Cancer Institute, 06100 Ankara, Turkey. * 3 Centre for Laboratory Animals Research and Application, Hacettepe University Ankara, Turkey; Department of Vaccine Technology, Vaccine Institute, Hacettepe University Ankara, Turkey. * 4 Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. * 5 Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. Electronic address: k.ozturk@hacettepe.edu.tr. * PMID: **42648563** * DOI: [ 10.1016/j.ijpharm.2026.127338 ](https://doi.org/10.1016/j.ijpharm.2026.127338) Item in Clipboard # Codelivery of nivolumab and galunisertib by EGFR-targeted spherical polymeric nanoparticles for effective treatment of non-small cell lung cancer Meryem Kaplan et al. Int J Pharm. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Pharm Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Pharm%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Pharm%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42648563/) . 2026 Oct 5:703:127338. doi: 10.1016/j.ijpharm.2026.127338. Epub 2026 Aug 26. ### Authors [Meryem Kaplan](https://pubmed.ncbi.nlm.nih.gov/?term=Kaplan+M&cauthor_id=42648563)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#short-view-affiliation-1 "Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey; Department of Pharmaceutical Technology, Faculty of Pharmacy, Süleyman Demirel University, 32260 Isparta, Turkey."), [Ece Tavukçuoğlu](https://pubmed.ncbi.nlm.nih.gov/?term=Tavuk%C3%A7uo%C4%9Flu+E&cauthor_id=42648563)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#short-view-affiliation-2 "Department of Basic Oncology, Hacettepe University Cancer Institute, 06100 Ankara, Turkey."), [Süleyman Can Öztürk](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%96zt%C3%BCrk+SC&cauthor_id=42648563)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#short-view-affiliation-3 "Centre for Laboratory Animals Research and Application, Hacettepe University Ankara, Turkey; Department of Vaccine Technology, Vaccine Institute, Hacettepe University Ankara, Turkey."), [Sema Çalış](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%87al%C4%B1%C5%9F+S&cauthor_id=42648563)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#short-view-affiliation-4 "Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey."), [Güneş Esendağlı](https://pubmed.ncbi.nlm.nih.gov/?term=Esenda%C4%9Fl%C4%B1+G&cauthor_id=42648563)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#short-view-affiliation-2 "Department of Basic Oncology, Hacettepe University Cancer Institute, 06100 Ankara, Turkey."), [Kivilcim Ozturk](https://pubmed.ncbi.nlm.nih.gov/?term=Ozturk+K&cauthor_id=42648563)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42648563/#short-view-affiliation-5 "Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. Electronic address: k.ozturk@hacettepe.edu.tr.") ### Affiliations * 1 Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey; Department of Pharmaceutical Technology, Faculty of Pharmacy, Süleyman Demirel University, 32260 Isparta, Turkey. * 2 Department of Basic Oncology, Hacettepe University Cancer Institute, 06100 Ankara, Turkey. * 3 Centre for Laboratory Animals Research and Application, Hacettepe University Ankara, Turkey; Department of Vaccine Technology, Vaccine Institute, Hacettepe University Ankara, Turkey. * 4 Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. * 5 Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. Electronic address: k.ozturk@hacettepe.edu.tr. * PMID: **42648563** * DOI: [ 10.1016/j.ijpharm.2026.127338 ](https://doi.org/10.1016/j.ijpharm.2026.127338) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract The incidence of cancer is among the leading causes of death worldwide, with more than 29 million people expected to be diagnosed by 2040. Despite advancements in cancer therapies, current immunotherapeutic approaches face challenges such as limited efficacy and off-target effects. To address these challenges, this study focuses on enhancing the efficacy of immunotherapeutics in the treatment of non-small cell lung cancer (NSCLC) through combination with a TGF-β inhibitor. A novel nanosystem was developed by co-loading galunisertib, a TGF-β inhibitor, and nivolumab, a PD-1 inhibitor, into spherical nanoparticles composed of PLGA derivatives conjugated with anti-EGFR for targeted delivery. In vitro characterization studies, including the nanoparticle size, zeta potential, morphology, drug release, toxicity evaluation in healthy and tumor cells, and T cell immune responses, demonstrated promising results. Based on these findings, in vivo studies were conducted on humanized mice that developed heterotopic xenograft tumors. In the concept of in vivo studies, biodistribution studies revealed that antibody-conjugated nanoparticles exhibited higher tumor accumulation compared to the control group. The targeted co-loaded nanoparticles maintained antitumor activity comparable to the free-drug combination while enabling tumor-directed delivery and showing a more favorable preliminary tolerability profile. **Keywords:** Drug delivery; Galunisertib; Immunotherapy; NSCLC; Nivolumab; PLGA; Polymeric nanoparticles. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kıvılcım Öztürk reports that financial support was provided by The Scientific and Technological Research Council of Turkey (TUBITAK) [Grant number: 119R055] and the Hacettepe University Scientific Research Projects Coordination Unit (Project No. THD-2023-20472). ## Similar articles * [ Red blood cell-conjugated biomimetic nanomedicine for enhanced therapy of non-small cell lung cancer. ](https://pubmed.ncbi.nlm.nih.gov/41695485/) Chiang ST, Jin Y, Zhao Q, Ling H, Xia Q, Han T, Li R, Li W, Lan Z, Ai X, Lu H.Chiang ST, et al.Theranostics. 2026 Jan 21;16(8):4147-4168. doi: 10.7150/thno.121646. eCollection 2026.Theranostics. 2026.PMID: 41695485Free PMC article. * [ Formulation and _in vitro_ Evaluation of Targeted Chemotherapy of Crizotinib-loaded polymeric Nanoparticles on Cancer Cell Lines. ](https://pubmed.ncbi.nlm.nih.gov/40820463/) Naureen F, Shah Y, Rehman MU, Alnemari RM.Naureen F, et al.Curr Pharm Des. 2026 Feb 6;32(13):1035-1050. doi: 10.2174/0113816128412622250730015435.Curr Pharm Des. 2026.PMID: 40820463 * [ Biomineralized microspheres trigger synergistic calcicoptosis-ferroptosis for enhanced non-small cell lung cancer therapy. ](https://pubmed.ncbi.nlm.nih.gov/41043671/) Yang L, Wang K, Dong J, Zhang X, Liu X, Cui J, Liu J, Zhou M, Wang K.Yang L, et al.Acta Biomater. 2025 Nov;207:617-632. doi: 10.1016/j.actbio.2025.09.053. Epub 2025 Oct 1.Acta Biomater. 2025.PMID: 41043671 * [ Nanotechnology Based Repositioning of an Anti-Viral Drug for Non-Small Cell Lung Cancer (NSCLC). ](https://pubmed.ncbi.nlm.nih.gov/32514688/) Parvathaneni V, Goyal M, Kulkarni NS, Shukla SK, Gupta V.Parvathaneni V, et al.Pharm Res. 2020 Jun 8;37(7):123. doi: 10.1007/s11095-020-02848-2.Pharm Res. 2020.PMID: 32514688 * [ Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway. ](https://pubmed.ncbi.nlm.nih.gov/26309397/) Herbertz S, Sawyer JS, Stauber AJ, Gueorguieva I, Driscoll KE, Estrem ST, Cleverly AL, Desaiah D, Guba SC, Benhadji KA, Slapak CA, Lahn MM.Herbertz S, et al.Drug Des Devel Ther. 2015 Aug 10;9:4479-99. doi: 10.2147/DDDT.S86621. eCollection 2015.Drug Des Devel Ther. 2015.PMID: 26309397Free PMC article.Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42648563) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42648563/) * Carcinoma, Non-Small-Cell Lung* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Carcinoma%2C+Non-Small-Cell+Lung%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Carcinoma%2C+Non-Small-Cell+Lung) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42648563/) * Carcinoma, Non-Small-Cell Lung* / pathology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Carcinoma%2C+Non-Small-Cell+Lung%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Carcinoma%2C+Non-Small-Cell+Lung) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42648563/) * Cell Line, Tumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%2C+Tumor%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line%2C+Tumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42648563/) * Drug Delivery Systems Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Drug+Delivery+Systems%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Drug+Delivery+Systems) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42648563/) * Drug Liberation Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Drug+Liberation%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Drug+Liberation) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42648563/) * ErbB Receptors / antagonists & inhibitors Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22ErbB+Receptors%2Fantagonists+and+inhibitors%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=ErbB+Receptors) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42648563/) * ErbB Receptors / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22ErbB+Receptors%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=ErbB+Receptors
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