Cisplatin-Encapsulated Polymeric Nanoparticles with Molecular Geometry-Regulated Colloidal Properties and Controlled Drug Release.

Encapsulation of chemotherapeutic agents inside a nanoscale delivery platform can provide an attractive therapeutic strategy with many pharmaceutical benefits, such as increased plasma solubility, prolonged in vivo circulation, and reduced acute toxicity. Given that the biological activities of polymeric nanoparticles are highly dependent on their colloidal structures, the molecular geometry-regulated programming of self-assembled nanoscale architecture is of great interest for chemical design of an ideal delivery platform. In this report, we demonstrate that the molecular geometry of block-copolymer excipients can govern the level of drug-loading capacity and core hydrophobicity of polymeric nanoparticles, which can eventually control the pH-sensitive drug-release property. Atom-transfer radical polymerization was employed as a controlled synthetic method for the copolymer excipients, which contain the metal-chelating poly(acrylic acid) block linked to either a small mPEG-grafted poly(methacrylate) to generate a bulky brush-like chains or a simple linear mPEG segment. During the coordination of cis-diammineplatinum(II) as an active pharmacophore of cisplatin, aqueous-phase size-exclusion chromatography analyses exhibited highly different self-association kinetic regimes prompted by versatile molecular geometry of copolymer excipients, which further allows us to explore the molecular geometry-colloidal property relationship.