ABSTRACT
Chemoradiotherapy is a well-established treatment paradigm in oncology. There has been strong interest in identifying strategies to further improve its therapeutic index. An innovative strategy is to utilize nanoparticle (NP) chemotherapeutics in chemoradiation. Since the most commonly utilized chemotherapeutic with radiotherapy is cisplatin, the development of an NP cisplatin for chemoradiotherapy has the highest potential impact on this treatment. Here, we report the development of an NP comprised of polysilsesquioxane (PSQ) polymer crosslinked by a cisplatin prodrug (Cisplatin-PSQ) and its utilization in chemoradiotherapy using non-small cell lung cancer as a disease model. Cisplatin-PSQ NP has an exceptionally high loading of cisplatin. Cisplatin-PSQ NPs were evaluated in chemoradiotherapy in vitro and in vivo. They demonstrated significantly higher therapeutic efficacy when compared to cisplatin. These results suggest that the Cisplatin-PSQ NP holds potential for clinical translation in chemoradiotherapy.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Non-Small-Cell Lung/therapy , Chemoradiotherapy/methods , Cisplatin/administration & dosage , Lung Neoplasms/therapy , Organosilicon Compounds/chemistry , Prodrugs/chemistry , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cisplatin/chemistry , Delayed-Action Preparations , Disease Models, Animal , Dose-Response Relationship, Drug , HL-60 Cells , Humans , Hydrodynamics , Mice , Microscopy, Electron, Scanning , Nanomedicine , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Polymers/chemistry , TemperatureABSTRACT
Nanoscale coordination polymers containing exceptionally high loadings of bisphosphonates were coated with single lipid bilayers to control the drug release kinetics and functionalized with a targeting ligand to endow cell-targeting capability, leading to much enhanced cytotoxicity against human lung and pancreatic cancer cells.
