Scalable Formulation and Production of Photosensitive Nanoparticles for Cancer Therapy

PROJECT SUMMARY Up toof treated women with early stage breast cancer will suffer from local recurrences on the chest wallRCWTreatment of local recurrences is problematic and surgery provides only ayear control rateRadiation therapy is a preferred optionbut efficacy is low for larger lesionsandgtcm diameterand additional rounds of radiation therapy are associated with other long term risks due to cumulative ionizing radiationPOP BiotechnologiesPOP BIOis advancing a relatively unexplored tumor treatment technique for RCW breast cancerchemo phototherapyCPTCPT involves the intravenous injection of long circulatingdoxorubicinloadedporphyrin phospholipidPoPliposomesNPfollowed by tumor irradiation with a near infraredNIRlaser resulting in the permeabilization of the liposomes and deposition of doxorubicin localized in the tumorAt presentfewif anylight controlled systems can achieve robuston demand spatial and temporal control of nanovesicle permeabilization in biological environmentsUnlike heat triggered drug release approachesNPis fully stable in serumyet rapidly release their contents when exposed to clinically relevant NIR laser irradiationIn mouse modelsa single mild laser treatment deposits large amounts of drugleading to permanent tumor eradicationIn this proposalPoP Biotechnologies will develop scalable liposome formulation protocols using a lipid extrusion approach and evaluate the resulting NPproductThis project has two specific aimsAimReproducibly produce and characterize doxorubicin loaded PoP liposomesNPusing a scalable approachand AimAssess in vivo pharmacokineticsefficacy and toxicity of NPin ratsPending a successful outcome of this Phase I grant applicationwe will put forward a Phase II grant application involving more in depth studies for treatment dosimetry and efficacy in large animals pertinent for translation to human trials PROJECT NARRATIVE The ability to selectively deliver drugs with precise spatial and temporal control could lead to entirely new approaches to treatments of solid tumorsWe have demonstrated anti tumor proof of principle for a new class of doxorubicin loaded long circulating liposomes that rapidly release drug in response to near infrared lighta safe and clinically proven stimulusA scalable manufacturing strategy for these liposomes will be developed and preliminary pharmacokineticsefficacyand toxicity in rats will be assessed