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CCR2-targeted micelles for anti-cancer peptide delivery and immune stimulation.
- Source :
-
Journal of Controlled Release . Jan2021, Vol. 329, p614-623. 10p. - Publication Year :
- 2021
-
Abstract
- Signaling between the C C chemokine receptor 2 (CCR2) with its ligand, monocyte chemoattractant protein-1 (MCP-1) promotes cancer progression by directly stimulating tumor cell proliferation and downregulating the expression of apoptotic proteins. Additionally, the MCP-1/CCR2 signaling axis drives the migration of circulating monocytes into the tumor microenvironment, where they mature into tumor-associated macrophages (TAMs) that promote disease progression through induction of angiogenesis, tissue remodeling, and suppression of the cytotoxic T lymphocyte (CTL) response. In order to simultaneously disrupt MCP-1/CCR2 signaling and target CCR2-expressing cancer cells for drug delivery, KLAK-MCP-1 micelles consisting of a CCR2-targeting peptide sequence (MCP-1 peptide) and the apoptotic KLAKLAK peptide were synthesized. In vitro , KLAK-MCP-1 micelles were observed to bind and induce cytotoxicity to cancer cells through interaction with CCR2. In vivo, KLAK-MCP-1 micelles inhibited tumor growth (34 ± 11%) in a subcutaneous B16F10 murine melanoma model despite minimal tumor accumulation upon intravenous injection. Tumors treated with KLAK-MCP1 demonstrated reduced intratumor CCR2 expression and altered infiltration of TAMs and CTLs as evidenced by immunohistochemical and flow cytometric analysis. These studies highlight the potential application of CCR2-targeted nanotherapeutic micelles in cancer treatment. Unlabelled Image • KLAK-MCP-1 micelles combine apoptotic peptides (KLAK) with CCR2-binding ligands (MCP-1) for targeted therapy of CCR2+ cancer. • KLAK-MCP-1 micelles exhibited CCR2-dependent binding and toxicity to cancer cells and monocytes in vitro. • KLAK-MCP-1 micelles inhibited tumor growth and altered tumor-infiltrating macrophage and cytotoxic T lymphocyte populations. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01683659
- Volume :
- 329
- Database :
- Academic Search Index
- Journal :
- Journal of Controlled Release
- Publication Type :
- Academic Journal
- Accession number :
- 148861541
- Full Text :
- https://doi.org/10.1016/j.jconrel.2020.09.054