Monoclonal antibody 2C5-modified mixed dendrimer micelles for tumor-targeted co-delivery of chemotherapeutics and siRNA.

Targeted delivery of chemotherapeutics to tumors has the potential to reach a high dose at the tumor while minimizing the systemic exposure. Incorporation of antibody within a micellar platform represents a drug delivery system for tumor-targeted delivery of anti-tumor agents. Such modified immunomicelles can result in an increased accumulation of anti-tumor agents and enhanced cytotoxicity towards cancer cells. Here, mixed dendrimer micelles (MDM) composed of PEG2k-DOPE-conjugated generation 4 polyamidoamine dendrimer G4-PAMAM-PEG2k-DOPE and PEG5k-DOPE were co-loaded with doxorubicin and siMDR-1. This formulation was further modified with monoclonal antibodies 2C5 with nucleosome-restricted specificity that effectively recognize cancer cells via the cell-surface-bound nucleosomes. Micelles with attached 2C5 antibodies significantly enhanced cellular association and tumor killing in both monolayer and spheroid tumor models as well as in vivo experimental animals compared to the non-targeted formulations.