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PDL1 Monoclonal Antibody-Modified mPEG-PLGA-NH2 Nanocomposite Loaded with Heterophyllin B for the Treatment of

Yunhai Wei1, Wenjing Hu2, Huancen Guo2

  • 1Department of Gastrointestinal Surgery, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University; Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou 313000, Zhejiang, China.

Journal of Medicinal Chemistry
|July 24, 2025
PubMed

Immune checkpoint inhibitors (ICIs) show effectiveness in gastric cancer (GC) treatment, yet enhancing their efficacy remains challenging. We encapsulated the anticancer compound Heterophyllin B (HB) in mPEG-PLGA-NH2 nanoparticles (NPs), modified with αPDL1, forming mPEG-PLGA-NH2@HB-αPDL1 NPs. These NPs displayed low toxicity to GES-1 cells and good blood compatibility. They effectively inhibited GC cell malignant phenotypes and downregulated PD-L1 expression via the PI3K/AKT pathway. In GC allograft mice, the HB and αPDL1 combination therapy outperformed monotherapy, with the NPs showing better efficacy than free drugs. Additionally, the NPs improved the tumor immune microenvironment. H&E staining confirmed no significant toxicity to major mouse organs. Thus, mPEG-PLGA-NH2@HB-αPDL1 offers a promising strategy for optimizing ICI therapy in GC treatment.

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Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...