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Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
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EGFR-targeted pemetrexed therapy of malignant pleural mesothelioma

Liang Yang1, Hanghang Fang1, Jingjing Jiang1

  • 1Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, People's Republic of China.

Drug Delivery and Translational Research
|November 21, 2021
PubMed

Insights

Targeted polymersomes loaded with pemetrexed (PEM) show improved chemotherapy for malignant pleural mesothelioma (MPM). This EGFR-targeted delivery enhances drug efficacy and tumor repression in preclinical models.

Area of Science:

  • Biomaterials Science
  • Nanomedicine
  • Oncology

Background:

  • Malignant pleural mesothelioma (MPM) is a rare cancer with limited treatment options and poor prognosis.
  • Current chemotherapy with pemetrexed (PEM) faces challenges including rapid clearance, low drug exposure, and dose-limiting toxicities.

Purpose of the Study:

  • To develop epidermal growth factor receptor (EGFR)-targeted polymersomes for enhanced delivery of PEM in MPM.
  • To evaluate the efficacy of EGFR-targeted polymersomes loaded with PEM in vitro and in vivo.

Main Methods:

  • Synthesized EGFR-targeted disulfide-crosslinked biodegradable chimaeric polymersomes (EGFR-CPs) encapsulating PEM.
  • Characterized EGFR-CPs-PEM nanoparticles for size and drug release properties.
  • Assessed cellular uptake and anticancer activity in EGFR-overexpressing MSTO-211H cells.
  • Evaluated in vivo tumor deposition, penetration, and therapeutic efficacy in an MSTO-211H xenograft mouse model.

Main Results:

  • EGFR-CPs-PEM nanoparticles (62-65 nm) demonstrated reduction-responsive PEM release.
  • Enhanced cellular uptake and a 4.7-fold increase in anticancer activity were observed in EGFR-overexpressing cells compared to non-targeted controls.
  • In vivo studies showed superior tumor deposition and penetration of EGFR-CPs-PEM.
  • EGFR-CPs-PEM significantly suppressed tumor growth more effectively than non-targeted polymersomes and free PEM.

Conclusions:

  • EGFR-targeted polymersomes provide an effective platform for delivering PEM in MPM.
  • This strategy overcomes limitations of free PEM, offering improved therapeutic outcomes.
  • Polymersome-enabled targeted delivery represents a promising therapeutic approach for MPM.
Keywords:
ChemotherapyEpidermal growth factor receptorMalignant pleural mesotheliomaPolymersomesTargeted delivery

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