Liang Pang1,2, Yihua Pei1, Gozde Uzunalli3, Hyesun Hyun1, L Tiffany Lyle3, Yoon Yeo4,5. 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.
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.
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.
Entities:
Keywords:
Drug delivery; M2pep; PLGA nanoparticles; PLX3397; tumor-associated macrophages
Authors: Cory M Alvey; Kyle R Spinler; Jerome Irianto; Charlotte R Pfeifer; Brandon Hayes; Yuntao Xia; Sangkyun Cho; P C P Dave Dingal; Jake Hsu; Lucas Smith; Manu Tewari; Dennis E Discher Journal: Curr Biol Date: 2017-06-29 Impact factor: 10.834
Authors: Antje Kroner; Andrew D Greenhalgh; Juan G Zarruk; Rosmarini Passos Dos Santos; Matthias Gaestel; Samuel David Journal: Neuron Date: 2014-08-14 Impact factor: 17.173
Authors: Song Shen; Hong-Jun Li; Kai-Ge Chen; Yu-Cai Wang; Xian-Zhu Yang; Zhe-Xiong Lian; Jin-Zhi Du; Jun Wang Journal: Nano Lett Date: 2017-05-16 Impact factor: 11.189
Authors: Kandice R Levental; Hongmei Yu; Laura Kass; Johnathon N Lakins; Mikala Egeblad; Janine T Erler; Sheri F T Fong; Katalin Csiszar; Amato Giaccia; Wolfgang Weninger; Mitsuo Yamauchi; David L Gasser; Valerie M Weaver Journal: Cell Date: 2009-11-25 Impact factor: 41.582
Authors: Chayanon Ngambenjawong; Maryelise Cieslewicz; Joan G Schellinger; Suzie H Pun Journal: J Control Release Date: 2016-01-07 Impact factor: 9.776
Authors: Jessica Hersh; David Broyles; José Manuel Condor Capcha; Emre Dikici; Lina A Shehadeh; Sylvia Daunert; Sapna Deo Journal: ACS Appl Bio Mater Date: 2020-12-24
Authors: Tetiana Hourani; James A Holden; Wenyi Li; Jason C Lenzo; Sara Hadjigol; Neil M O'Brien-Simpson Journal: Front Oncol Date: 2021-12-20 Impact factor: 6.244