Erythrocyte-derived nanoparticles for light activated combination of chemo-photothermal therapy of tumors

Project Summary Abstract This project is aimed at developing a novel type of nanoparticle formulation for targeted chemo phototherapeutic destruction of tumorsSpecificallythese nanoparticles are hybrid structures composed of erythrocyte derived vesicles doped with two FDA approved agentsthe near infraredNIRchromophoreindocyanine greenICGand chemotherapeutic drugdoxorubicin hydrochlorideDOXFurthermorethe surface of the nanoparticles is functionalized with the FDA approved humanized monoclonal antibodiesHerceptinfor molecular targeting of the human epidermal growth factor receptorHERwhose over expression is associated with the carcinogenesis of various solid tumorsWe refer to these nanoparticles as ICG andampDOX loaded NIR erythrocyte derived transducersID NETsUpon activation by an appropriate NIR wavelengththey can transduce the absorbed light energy to generate heat for photothermal destruction of tumorand also trigger the release of DOX into the tumor siteWe hypothesize that the local delivery of ID NETs into tumors along with combined dual photothermal chemotherapeutic effects will lower the optical and drug dosages necessary for destruction of tumors than the corresponding dosages associated with the single modality treatmentThis approach should ultimately lead to enhanced therapeutic outcomesand reduce side effects that may otherwise result from the systemic delivery of chemotherapeutic agentsparticularly at higher dosagesOur long term goal is to commercialize ID NETs as an agent for chemophototherapeutic destruction of tumorsThere are no prior reports of an erythrocyte derived nanoparticle formulation for targeted chemo phototherapeutic destruction of tumorsThereforethis proposal presents a highly innovative technology in treating tumorsand the first step in investigating the potential of these nanoparticles for future clinical translationOur specific aimsSAsduring this Phase I project are tofabricatecharacterize and optimize the formulation of ID NETs for maximum ICG and DOX loadingSAinvestigate the effects of pH and laser power densities on the release kinetics of ICG and DOX from a series of ID NETs formulationsSAvalidate the effectiveness of Herceptinfunctionalized ID NETs for targeted in vitro chemo photothermal destruction of cancer cellsSAInvestigate the utility of Herceptinfunctionalized ID NETs in mediating chemo photothermal therapy of tumors in miceSAUpon completion of the proposed Phase I studieswe will identify the optimum formulation of Herceptinfunctionalized ID NETs for maximum ICG and DOX loadingand demonstrate the feasibility for targeted chemophotothermal therapy of tumorsOur activities during Phase II will include the development of fabrication standardization procedures and full commercialization plansGiven the existing FDA approved status of ICGDOXHerceptinand prior clinical studies with erythrocytes based delivery systemsID NETs present a promising candidate for clinical translationThis Phase I application is the first step towards these endeavors Project Narrative This project is aimed at developing a novel type of nanoparticle formulation derived from red blood cells for intraoperative destruction of tumors by combining molecular targeting of specific cancer cell biomarkers with a dual chemo phototherapeutic modalityOur long term goal is to commercialize these nanoparticles as an agent for targeted chemo photothermal therapyWe expect that the proposed therapeutic technology will have tremendous clinical impact in cancer treatmentand ultimatelyimprove patient response and survival