4.7 Article

Targeting of Tumor-Associated Macrophages Made Possible by PEG-Sheddable, Mannose-Modified Nanoparticles

Journal

MOLECULAR PHARMACEUTICS
Volume 10, Issue 9, Pages 3525-3530

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/mp400216r

Keywords

tumor-associated macrophages; nanoparticles; mannose receptor; acid-sensitivity; PEGylation

Funding

  1. National Cancer Institute [CA135274]
  2. Cancer Prevention and Research Institute of Texas (CPRIT) [RPI01501]

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It is increasingly evident that tumor-. associated macrophages (TAMs) play an important role in tumor invasion, proliferation, and metastasis. While delivery of drugs, imaging agents, and vaccines to TAMs. was achieved by exploiting membrane receptors on TAMs, the uptake by normal macrophages remains an issue. In this communication, we report a PEG-sheddable, mannose-modified nanoparticle platform that can efficiently target TAMs via mannose7mannose receptor recognition :after acid sensitive PEG shedding in the acidic tumor..micrOenviromiient, while their :uptake by normal macrophages in the mononuclear :phagocyte System (MPS) organs: was significantly reduced due; to :effective PEG,Shielding at neutral pH. These nanoparticles have the potential to target drugs of interest to TAMs, with decreased uptake by normal :Macrophage's.

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