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
  • 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. [email protected].
  • 5. Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, Indiana, 47907, USA. [email protected].
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.
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