2. Academic Validation
  3. Surface Modification of Polymeric Nanoparticles with M2pep Peptide for Drug Delivery to Tumor-Associated Macrophages

Surface Modification of Polymeric Nanoparticles with M2pep Peptide for Drug Delivery to Tumor-Associated Macrophages

  • Pharm Res. 2019 Mar 11;36(4):65. doi: 10.1007/s11095-019-2596-5.
Liang Pang 1 2,  Yihua Pei 1,  Gozde Uzunalli 3,  Hyesun Hyun 1,  L Tiffany Lyle 3,  Yoon Yeo 4 5
Affiliations

Affiliations

  • 1 Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA.
  • 2 Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
  • 3 Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, 47907, USA.
  • 4 Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA. yyeo@purdue.edu.
  • 5 Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, Indiana, 47907, USA. yyeo@purdue.edu.
PMID: 30859335 DOI: 10.1007/s11095-019-2596-5
Abstract

Purpose: Tumor-associated macrophages (TAMs) with immune-suppressive M2-like phenotype constitute a significant part of tumor and support its growth, thus making an attractive therapeutic target for Cancer therapy. To improve the delivery of drugs that control the survival and/or functions of TAMs, we developed nanoparticulate drug carriers with high affinity for TAMs.

Methods: Poly(lactic-co-glycolic acid) nanoparticles were coated with M2pep, a peptide ligand selectively binding to M2-polarized macrophages, via a simple surface modification method based on tannic acid-iron complex. The interactions of M2pep-coated nanoparticles with macrophages of different phenotypes were tested in vitro and in vivo. PLX3397, an inhibitor of the colony stimulating factor-1 (CSF-1)/CSF-1 receptor (CSF-1R) pathway and macrophage survival, was delivered to B16F10 tumors via M2pep-modified PLGA nanoparticles.

Results: In bone marrow-derived macrophages polarized to M2 phenotype, M2pep-coated nanoparticles showed greater cellular uptake than those without M2pep. Consistently, M2pep-coated nanoparticles showed relatively high localization of CD206+ macrophages in B16F10 tumors. PLX3397 encapsulated in M2pep-coated nanoparticles attenuated tumor growth better than the free drug counterpart.

Conclusion: These results support that M2pep-coating can help nanoparticles to interact with M2-like TAMs and facilitate the delivery of drugs that control the tumor-supportive functions of TAMs.

Keywords

Drug delivery; M2pep; PLGA nanoparticles; PLX3397; tumor-associated macrophages.

Figures
Products