1R43CA228707-01A1 (R43) ApplID: 9622719 | |||
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Title | Scalable Formulation and Production of Photosensitive Nanoparticles for Cancer Therapy | ||
Institution | POP BIOTECHNOLOGIES, LLC, BUFFALO, NY | ||
Principal Investigator | CARTER, KEVIN | NCI Program Director | Kurtz |
Cancer Activity | Small Business - Cancer Treatment/ Therapy | Division | SBIRDC |
Funded Amount | $224,205 | Project Dates | 09/06/2018 - 08/31/2019 |
Fiscal Year | 2018 | Project Type | Grant |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) Chemotherapy (100.0%) |
Breast (100.0%) | ||
Research Type | |||
Systemic Therapies - Discovery and Development | |||
Abstract | |||
PROJECT SUMMARY Up to 20% of treated women with early stage breast cancer will suffer from local recurrences on the chest wall (RCW). Treatment of local recurrences is problematic and surgery provides only a 33% 5-year control rate. Radiation therapy is a preferred option, but efficacy is low for larger lesions (>3 cm diameter) and additional rounds of radiation therapy are associated with other long-term risks due to cumulative ionizing radiation. POP Biotechnologies (POP BIO) is advancing a relatively unexplored tumor-treatment technique for RCW breast cancer: chemo-phototherapy (CPT). CPT involves the intravenous injection of long-circulating, doxorubicin- loaded, porphyrin-phospholipid (PoP) liposomes (NP-01) followed by tumor irradiation with a near infrared (NIR) laser resulting in the permeabilization of the liposomes and deposition of doxorubicin localized in the tumor. At present, few, if any, light-controlled systems can achieve robust, on-demand spatial and temporal control of nanovesicle permeabilization in biological environments. Unlike heat-triggered drug release approaches, NP-01 is fully stable in serum, yet rapidly release their contents when exposed to clinically-relevant NIR laser irradiation. In mouse models, a single mild laser treatment deposits large amounts of drug, leading to permanent tumor eradication. In this proposal, PoP Biotechnologies will develop scalable liposome formulation protocols using a lipid extrusion approach and evaluate the resulting NP-01 product. This project has two specific aims: Aim 1: Reproducibly produce and characterize doxorubicin-loaded PoP liposomes (NP-01) using a scalable approach; and Aim 2: Assess in vivo pharmacokinetics, efficacy and toxicity of NP-01 in rats. Pending a successful outcome of this Phase I grant application, we 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." |