title: Polysilsesquioxane nanoparticles for triggered release of cisplatin and effective cancer chemoradiotherapy.
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.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Joseph Della
authors.initials: JD
authors.lastname: Rocca
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, CB 7512 University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Werner
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Kramer
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Huxford-Phillips
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, CB 7512 University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Sukumar
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, CB 7512 University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Cummings
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Vivero-Escoto
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, CB 7512 University of North Carolina School of Medicine, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: zawang@med.unc.edu.
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Department of Chemistry, University of Chicago, Chicago, IL, USA. Electronic address: wenbinlin@uchicago.edu.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D057446:Hydrodynamics; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry; D017646:Organosilicon Compounds / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry*; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D017646:Organosilicon Compounds; D011108:Polymers; D011355:Prodrugs; C569780:polysilsesquioxane; D011092:Polyethylene Glycols; D002945:Cisplatin
keywords: Cancer chemoradiotherapy; Cisplatin; Hybrid nanomaterials; Lung cancer; Nanomedicine; Polysilsesquioxane; Silica