2. Academic Validation
  3. CD44-targeted nanoparticles for remodeling the tumor microenvironment in a 3D macrophage-embedded ovarian cancer model with stem cell-like features

CD44-targeted nanoparticles for remodeling the tumor microenvironment in a 3D macrophage-embedded ovarian cancer model with stem cell-like features

  • Int J Pharm. 2025 Mar 16:674:125483. doi: 10.1016/j.ijpharm.2025.125483.
Samjhana Shrestha 1,  Anil Giri 2,  Prabhat Shrestha 2,  Seho Kweon 3,  In-Sun Hong 4,  Taeg Kyu Kwon 5,  Jong-Sun Kang 6,  Jee-Heon Jeong 7,  Ha Rin Kim 8,  Simmyung Yook 9
Affiliations

Affiliations

  • 1 College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea.
  • 2 Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea.
  • 3 College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.
  • 4 Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840, Republic of Korea.
  • 5 Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea.
  • 6 Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea.
  • 7 Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea.
  • 8 Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea; Department of Biopharmaceutical Chemistry, Kookmin University, Seoul, Republic of Korea. Electronic address: harinkim@kookmin.ac.kr.
  • 9 Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: ysimmyung@skku.edu.
PMID: 40101874 DOI: 10.1016/j.ijpharm.2025.125483
Abstract

Ovarian Cancer frequently develops resistance to chemotherapy, which is driven by Cancer Stem Cells (CSCs) and an immunosuppressive tumor microenvironment (TME) shaped by tumor-associated macrophages (TAMs). This study explored the therapeutic potential of CD44-targeted, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CD44-PLGA-DTX NPs) in overcoming chemoresistance in ovarian Cancer. A 3D spheroidal model incorporating SKOV3 ovarian Cancer cells and TAMs was developed to mimic the TME for in vitro investigations. CD44-PLGA-DTX NPs exhibited significantly enhanced cellular uptake within the macrophage-embedded SKOV3 spheroids, which resulted in reduced cell viability and a reversal of chemoresistance. Cytokine profiling further revealed that the NPs promoted TAM polarization from the protumor M2 phenotype to the antitumor M1 phenotype, thus fostering an antitumor immune environment. These findings highlight the potential of CD44-targeted NPs as a dual-targeted therapeutic strategy, targeting both CSCs-driven tumor growth and TME reprogramming, thereby improving ovarian Cancer treatment outcomes.

Keywords

3D spheroid; CD44-antibody; Nanoparticles; Ovarian cancer stem cells; PLGA.

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