CCR2-targeted micelles for anti-cancer peptide delivery and immune stimulation

Area of Science:

• Oncology
• Nanomedicine
• Immunology

Background:

• CC chemokine receptor 2 (CCR2) and its ligand, monocyte chemoattractant protein-1 (MCP-1), drive cancer progression by promoting tumor cell proliferation and immune suppression.
• MCP-1/CCR2 signaling facilitates the recruitment of monocytes, which differentiate into tumor-associated macrophages (TAMs), further promoting tumor growth, angiogenesis, and immune evasion.

Purpose of the Study:

• To develop and evaluate KLAK-MCP-1 micelles for simultaneous disruption of MCP-1/CCR2 signaling and targeted delivery to CCR2-expressing cancer cells.
• To assess the in vitro and in vivo efficacy of KLAK-MCP-1 micelles in inhibiting cancer progression.

Main Methods:

• Synthesis of KLAK-MCP-1 micelles incorporating a CCR2-targeting peptide (MCP-1 peptide) and an apoptotic peptide (KLAKLAK).
• In vitro assessment of micelle binding and cytotoxicity in cancer cells via CCR2 interaction.
• In vivo evaluation of KLAK-MCP-1 micelles in a subcutaneous B16F10 murine melanoma model, including tumor growth inhibition, CCR2 expression, TAM, and cytotoxic T lymphocyte (CTL) infiltration analysis.

Main Results:

• KLAK-MCP-1 micelles demonstrated binding and induced cytotoxicity in cancer cells through CCR2 interaction in vitro.
• In vivo, KLAK-MCP-1 micelles significantly inhibited tumor growth by 34% in a B16F10 melanoma model.
• Treatment with KLAK-MCP1 micelles led to reduced intratumor CCR2 expression and altered TAM and CTL infiltration.

Conclusions:

• KLAK-MCP-1 micelles show potential as a dual-action nanotherapeutic agent for cancer treatment.
• Targeting the MCP-1/CCR2 axis with nanomicelles offers a promising strategy for inhibiting tumor progression and modulating the tumor immune microenvironment.