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Pharmaceutical Research

, 36:65 | Cite as

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

  • Liang Pang
  • Yihua Pei
  • Gozde Uzunalli
  • Hyesun Hyun
  • L. Tiffany Lyle
  • Yoon YeoEmail author
Research Paper
Part of the following topical collections:
  1. Nanomedicines in Cancer

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.

KEY WORDS

Drug delivery M2pep PLGA nanoparticles PLX3397 tumor-associated macrophages 

Notes

Acknowledgments and Disclosures

This work was supported by NIH R01 EB017791, NIH R01 CA232419, and the fellowship support from the China Scholarship Council Fellowship to L.P.

Supplementary material

11095_2019_2596_MOESM1_ESM.pdf (4.4 mb)
ESM 1 (PDF 4.42 mb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Industrial and Physical PharmacyPurdue UniversityWest LafayetteUSA
  2. 2.Department of PharmacyThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  3. 3.Department of Comparative PathobiologyPurdue UniversityWest LafayetteUSA
  4. 4.Weldon School of Biomedical EngineeringPurdue UniversityWest LafayetteUSA

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