Cholesterol-tethered platinum II-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity

摘要: Nanoscale drug delivery vehicles have been harnessed extensively as carriers for cancer chemotherapeutics. However, traditional pharmaceutical approaches nanoformulation a challenge with molecules that exhibit incompatible physicochemical properties, such platinum-based Here we propose paradigm based on rational design of active facilitate supramolecular assembly in the nanoscale dimension. Using cisplatin template, describe synthesis unique platinum (II) tethered to cholesterol backbone via monocarboxylato and O→Pt coordination environment facilitates nanoparticle fixed ratio phosphatidylcholine 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000]. The nanoparticles formed lower IC50 values compared carboplatin or vitro, are cisplatin-resistant conditions. Additionally, significantly enhanced vivo antitumor efficacy murine 4T1 breast K-RasLSL/+/Ptenfl/fl ovarian models decreased systemic- nephro-toxicity. Our results indicate integrating nanochemistry can emerge powerful strategy development. Furthermore, given chemotherapeutics form frontline therapy broad range cancers, increased toxicity profile constructed nanostructure could translate into next-generation agent clinics.