Matches in SemOpenAlex for { <https://semopenalex.org/work/W1990624197> ?p ?o ?g. }
Showing items 1 to 82 of
82
with 100 items per page.
- W1990624197 abstract "chemoradiation therapy regimens, cisplatin is one of the most commonly utilized agents. Although cisplatin is highly effective as a radiosensitizer, its use has been limited by toxicity. Therefore, one of the goals of radiation oncology research has been identifying methods to improve cisplatin’s efficacy while lowering its toxicity. While traditional drug delivery strategies such as intra-arterial delivery have failed, the development of nanoparticle (NP) drug delivery vehicles offers an unprecedented opportunity. NPs are known to preferentially accumulate in tumors while depositing lower dose to normal tissues such as kidneys. Such unique biodistribution is ideally suited for chemoradiation therapy. We hypothesized that the development of a NP formulation of cisplatin can improve therapeutic efficacy and lower the toxicity of cisplatin-based chemoradiation therapy. Materials/Methods: We have developed a novel formulation of cisplatin using the Polysilsesquoxane (PSQ) NP platform. The cisplatin-PSQ NPs were characterized physically using transmission electron microscopy. Its drug release profile was determined. First, we evaluated cisplatin-PSQ NP as a radiosensitizer in vitro using non-small cell lung cancer (NSCLC) cells lines H460 and A549. We then compared the toxicity profiles of cisplatin-PSQ NP to that of cisplatin in vivo. The efficacy of cisplatin-PSQ NP in chemoradiation therapy was compared to that of cisplatin using mouse models of NSCLC. Results: Cisplatin-PSQ NPs were w65 nm in diameter with cisplatin loading of up to 42% (weight) of NP. The cisplatin-PSQ NPs were highly stable with minimal drug release in neutral pH. Cisplatin release was rapid from NPs in reducing environments similar to that of tumor. In vitro evaluation showed cisplatin-PSQ NP is an excellent radiosensitizer with radiation survival curves similar to that of cisplatin. Toxicity evaluations showed cisplatin-PSQ NP has a significantly lower toxicity overall toxicity profile than that of cisplatin. Furthermore, cisplatin-PSQ NP has lower renal toxicity than cisplatin. Lastly, we demonstrated that cisplatin-PSQ NP is more effective than cisplatin in chemoradiation therapy using two mouse xenograft models of NSCLC. Conclusions: We have engineered a novel NP formulation of cisplatin. Cisplatin-PSQ NP has been shown to have lower toxicity and higher efficacy than cisplatin in chemoradiation therapy using NSCLC as a model disease. We believe cisplatin-PSQ is a promising radiosensitizer with high potential for clinical translation. Author Disclosure: A.Z. Wang: P. Ownership Other; Co-Founder, Coordination Therapeutics, Inc. J. Della Rocca: None. N.D. Cummings: None. R. Sukumar: None. M.E. Werner: None. W. Lin: P. Ownership Other; CoFounder, Coordination Therapeutics, Inc." @default.
- W1990624197 created "2016-06-24" @default.
- W1990624197 creator A5008979088 @default.
- W1990624197 creator A5019874592 @default.
- W1990624197 creator A5082801249 @default.
- W1990624197 creator A5086139889 @default.
- W1990624197 date "2012-11-01" @default.
- W1990624197 modified "2023-09-27" @default.
- W1990624197 title "Preclinical Investigation of Hsp27 LNA as a Novel Radiosensitizer in Head-and-Neck Cancer" @default.
- W1990624197 doi "https://doi.org/10.1016/j.ijrobp.2012.07.1846" @default.
- W1990624197 hasPublicationYear "2012" @default.
- W1990624197 type Work @default.
- W1990624197 sameAs 1990624197 @default.
- W1990624197 citedByCount "0" @default.
- W1990624197 crossrefType "journal-article" @default.
- W1990624197 hasAuthorship W1990624197A5008979088 @default.
- W1990624197 hasAuthorship W1990624197A5019874592 @default.
- W1990624197 hasAuthorship W1990624197A5082801249 @default.
- W1990624197 hasAuthorship W1990624197A5086139889 @default.
- W1990624197 hasConcept C126322002 @default.
- W1990624197 hasConcept C143998085 @default.
- W1990624197 hasConcept C150903083 @default.
- W1990624197 hasConcept C171250308 @default.
- W1990624197 hasConcept C192562407 @default.
- W1990624197 hasConcept C207001950 @default.
- W1990624197 hasConcept C2776428644 @default.
- W1990624197 hasConcept C2776530083 @default.
- W1990624197 hasConcept C2776694085 @default.
- W1990624197 hasConcept C2777807558 @default.
- W1990624197 hasConcept C2778239845 @default.
- W1990624197 hasConcept C2779820397 @default.
- W1990624197 hasConcept C29730261 @default.
- W1990624197 hasConcept C502942594 @default.
- W1990624197 hasConcept C509974204 @default.
- W1990624197 hasConcept C71924100 @default.
- W1990624197 hasConcept C86803240 @default.
- W1990624197 hasConcept C98274493 @default.
- W1990624197 hasConceptScore W1990624197C126322002 @default.
- W1990624197 hasConceptScore W1990624197C143998085 @default.
- W1990624197 hasConceptScore W1990624197C150903083 @default.
- W1990624197 hasConceptScore W1990624197C171250308 @default.
- W1990624197 hasConceptScore W1990624197C192562407 @default.
- W1990624197 hasConceptScore W1990624197C207001950 @default.
- W1990624197 hasConceptScore W1990624197C2776428644 @default.
- W1990624197 hasConceptScore W1990624197C2776530083 @default.
- W1990624197 hasConceptScore W1990624197C2776694085 @default.
- W1990624197 hasConceptScore W1990624197C2777807558 @default.
- W1990624197 hasConceptScore W1990624197C2778239845 @default.
- W1990624197 hasConceptScore W1990624197C2779820397 @default.
- W1990624197 hasConceptScore W1990624197C29730261 @default.
- W1990624197 hasConceptScore W1990624197C502942594 @default.
- W1990624197 hasConceptScore W1990624197C509974204 @default.
- W1990624197 hasConceptScore W1990624197C71924100 @default.
- W1990624197 hasConceptScore W1990624197C86803240 @default.
- W1990624197 hasConceptScore W1990624197C98274493 @default.
- W1990624197 hasLocation W19906241971 @default.
- W1990624197 hasOpenAccess W1990624197 @default.
- W1990624197 hasPrimaryLocation W19906241971 @default.
- W1990624197 hasRelatedWork W1798811923 @default.
- W1990624197 hasRelatedWork W1847133516 @default.
- W1990624197 hasRelatedWork W2018558719 @default.
- W1990624197 hasRelatedWork W2034702640 @default.
- W1990624197 hasRelatedWork W2040273337 @default.
- W1990624197 hasRelatedWork W2052360808 @default.
- W1990624197 hasRelatedWork W2069169798 @default.
- W1990624197 hasRelatedWork W2101599998 @default.
- W1990624197 hasRelatedWork W2106928478 @default.
- W1990624197 hasRelatedWork W2114304955 @default.
- W1990624197 hasRelatedWork W2154136969 @default.
- W1990624197 hasRelatedWork W2391880949 @default.
- W1990624197 hasRelatedWork W2559907794 @default.
- W1990624197 hasRelatedWork W2603200727 @default.
- W1990624197 hasRelatedWork W2740403319 @default.
- W1990624197 hasRelatedWork W2913940592 @default.
- W1990624197 hasRelatedWork W386288231 @default.
- W1990624197 hasRelatedWork W2083903934 @default.
- W1990624197 hasRelatedWork W2180709006 @default.
- W1990624197 hasRelatedWork W3140201719 @default.
- W1990624197 isParatext "false" @default.
- W1990624197 isRetracted "false" @default.
- W1990624197 magId "1990624197" @default.
- W1990624197 workType "article" @default.