Panitumumab-Conjugated Pt-Drug Nanomedicine for Enhanced Efficacy of Combination Targeted Chemotherapy against Colorectal Cancer.

Abstract

Targeted combination chemotherapy (TCT) has recently been used to increase the induction of tumor cell death. In particular, the combination of Panitumumab and the platinum (Pt)-derived chemotherapeutic drug Oxaliplatin is clinically effective against KRAS and BRAF wild-type colorectal cancer (CRC) cells that overexpress epidermal growth factor receptors, and significantly greater efficacy is observed than with either drug alone. However, low accumulation of Pt drug in tumor sites prevents achievement of ideal efficacy. To develop an alternative drug therapy that achieves the ideal efficacy of TCT, the novel nanomedicine NANO_Pt-Pan using self-assembled dichloro(1,2-diaminocyclohexane)Pt(II)-modified Panitumumab is generated. Treatments with NANO_Pt-Pan lead to significant accumulation of Pt drug and Panitumumab in tumors, reflecting enhanced permeability and retention effect, active targeting, and sustained circulation of the Pt drug in the blood. In addition, NANO_Pt-Pan has excellent in vivo anti-CRC efficacy. These data indicate that NANO_Pt-Pan has high potential as a candidate nanomedicine for CRC.