Preparation of cisplatin delivery calcium phosphate nanoparticles using poly(Pt(IV) prodrug) as the payload

Abstract

Directly encapsulating cisplatin in calcium phosphate nanoparticles (CPNPs) is a challenge because of the low water-solubility and weak binding affinity with calcium phosphate (CaP) of the cisplatin. In this work, we present a unique strategy using a polymer (poly(Pt(IV) prodrug)) bearing numerous carboxyl side groups and incorporating redox-sensitive cisplatin Pt(IV) prodrugs in its backbone as the payload for encapsulation in CPNPs. The poly(Pt(IV) prodrug) was efficiently encapsulated in CPNPs (>90 %), attributing to its improved solubility in alkaline water and strong binding affinity with CaP deriving from the plenty of carboxyl side groups. The CPNPs were stable and almost entirely inhibited the premature release of platinum drugs in the medium mimicking the pH condition of the bloodstream, whether there were reduction agents or not. While in an acidic condition with reduction agents, they released platinum drugs rapidly due to simultaneous reduction and hydrolysis of the poly(Pt(IV) prodrug). Further bioactivity experiments demonstrated the poly(Pt(IV) prodrug) encapsulated CPNPs were of higher efficacy against cancerous cells than free cisplatin and poly(Pt(IV) prodrug) owing to the enhanced platinum drugs uptake by cancerous cells via the CPNPs.