Multifunctional Hollow Gold Nanospheres for Concurrent Photothermal-Chemotherapy

DESCRIPTION provided by applicant Treatment of patients with primary and metastatic liver tumors is a challenging unsolved problem Only of patients with tumors in the liver are surgical candidates and systemic chemotherapy alone has been demonstrated to be of limited efficacy in treating hepatocellular carcinoma and liver metastases Minimally invasive image guided interventional techniques including transarterial interventions and percutaneous interventions e g radiofrequency ablation laser ablation have been introduced into the clinic for the treatment of patients with liver tumors However these techniques are limited by incomplete elimination of cancer cells which can lead to local tumor recurrence Therefore there is an urgent need to develop innovative local treatment approaches for liver tumors We believe that intraarterially delivered nanoparticles offers a unique opportunity for highly concentrated local delivery of heat and chemotherapeutic agents and thus may significantly improve the efficacy of treatment for liver tumors We have developed an innovative proprietary technology that is capable of mediating simultaneous near infrared laser triggered photothermal ablation PTA and local release of doxorubicin DOX Our DOX loaded polyethylene glycol coated hollow gold nanospheres DOX@PEG HAuNS have demonstrated low systemic toxicity under normal body temperatures and significantly enhanced antitumor efficacy when combined with laser exposure under hyperthermia and ablative temperatures In this SBIR program we have assembled a multidisciplinary team to implement a coherent strategy to address developmental and translational challenges Our specific aims are To synthesize and characterize high quality DOX@PEG HAuNS in large scale and under Good laboratory Practice GLP production conditions To determine the pharmacokinetics PK and biodistribution of DOX@PEG HAuNS after IA injection in rats and to demonstrate the feasibility of concurrent PTA and DOX chemotherapy in an orthotopic rat liver cancer model and a clinically relevant large animal liver cancer model rabbit VX model We believe that the proposed dual modality treatment strategy will offer superior local tumor control while reducing the likelihood of adverse events Success of the proposed work will pave the way for future clinical trials of DOX@PEG HAuNS PUBLIC HEALTH RELEVANCE The mortality associated with primary and metastatic liver tumors remains high and novel treatments for liver tumors are urgently needed The current project offers a minimally invasive treatment strategy that combines image guided photothermal ablation with chemotherapy This strategy when successfully introduced into the clinic will fulfil the unmet clinical need for better treatment for unresectable primary and metastatic liver tumors