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Cited by 187

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CSF1R‐ and SHP2‐Inhibitor‐Loaded Nanoparticles Enhance Cytotoxic Activity and Phagocytosis in Tumor‐Associated Macrophages

Ramesh, Anujan, Kumar, Sahana, Nandi, Dipika, Kulkarni, Ashish·2019·Advanced Materials

Abstract

Immune modulation of macrophages has emerged as an attractive approach for anti‐cancer therapy. However, there are two main challenges in successfully utilizing macrophages for immunotherapy. First, macrophage colony stimulating factor (MCSF) secreted by cancer cells binds to colony stimulating factor 1 receptor (CSF1‐R) on macrophages and in turn activates the downstream signaling pathway responsible for polarization of tumor‐associated macrophages (TAMs) to immunosuppressive M2 phenotype. Second, ligation of signal regulatory protein α (SIRPα) expressed on myeloid cells to CD47, a transmembrane protein overexpressed on cancer cells, activates the Src homology region 2 (SH2) domain ‐phosphatases SHP‐1 and SHP‐2 in macrophages. This results in activation of “eat‐me‐not” signaling pathway and inhibition of phagocytosis. Here, it is reported that self‐assembled dual‐inhibitor‐loaded nanoparticles (DNTs) target M2 macrophages and simultaneously inhibit CSF1R and SHP2 pathways. This results in efficient repolarization of M2 macrophages to an active M1 phenotype, and superior phagocytic capabilities as compared to individual drug treatments. Furthermore, suboptimal dose administration of DNTs in highly aggressive breast cancer and melanoma mouse models show enhanced anti‐tumor efficacy without any toxicity. These studies demonstrate that the concurrent inhibition of CSF1‐R and SHP2 signaling pathways for macrophage activation and phagocytosis enhancement could be an effective strategy for macrophage‐based immunotherapy.

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Metadata

Authors
Ramesh, A., Kumar, S., Nandi, D., & Kulkarni, A.
Venue
Advanced Materials
Publisher
Wiley
Published
2019-10-29
Volume
31
Issue
51
Pages
e1904364-e1904364
ISSN
  • 0935-9648 (ISSN-L)
  • 1521-4095
OpenAlex
W2982315700
Cited by
187
References
10
FWCI
8.09
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: CSF1R‐ and SHP2‐Inhibitor‐Loaded Nanoparticles Enhance Cytotoxic Activity and Phagocytosis in Tumor‐Associated Macrophages. https://app.cochat.ai/papers/10.1002/adma.201904364
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Ramesh, A., Kumar, S., Nandi, D., & Kulkarni, A. (2019). CSF1R‐ and SHP2‐Inhibitor‐Loaded Nanoparticles Enhance Cytotoxic Activity and Phagocytosis in Tumor‐Associated Macrophages. Advanced Materials. https://doi.org/10.1002/adma.201904364

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