Targeting cells of the immune system: mannosylated HPMA–LMA block-copolymer micelles for targeting of dendritic cells

Abstract

Background: Successful tumor immunotherapy depends on the induction of strong and sustained tumor antigen-specific immune responses by activated antigen-presenting cells (APCs) such as dendritic cells (DCs). Since nanoparticles have the potential to codeliver tumor-specific antigen and DC-stimulating adjuvant in a DC-targeting manner, we wanted to assess the suitability of mannosylated HPMA-LMA block polymers for immunotherapy. Materials & methods: Fluorescence-labeled block copolymer micelles derived from P(HPMA)-block-P(LMA) copolymers and according statistical copolymers were synthesized via RAFT polymerization, and loaded with the APC activator L18-MDP. Both types of copolymers were conjugated with D-mannose to target the mannose receptor as expressed by DCs and macrophages. The extent and specificity of micelle binding and activation of APCs was monitored using mouse spleen cells and bone marrow-derived DC (BMDC). Results: Nontargeting HPMA-LMA statistical copolymers showed strong unspecific cell binding. HPMA-LMA block copolymers bound DC only when conjugated with mannose, and in a mannose receptor-specific manner. Mannosylated HPMA-LMA block copolymers were internalized by DC. DC-targeting HPMA-LMA block copolymers mediated DC activation when loaded with L18-MDP. Conclusion: Mannosylated HPMA-LMA block copolymers are a promising candidate for the delvopment of DC-targeting nanovaccines.