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Supported by

IndoUS Science and Technology Fund

Principal Investigators:

Dr. Srinivas Sridhar,Ph.D.

NSF IGERT Nanomedicine Science and Technology Centre, Electronic Materials Research Institute, Northeastern University, MA 

Dr. R. C. Budhani,Ph.D.

National Physical Laboratory, New Delhi 

Dr. Surinder P Singh, Ph.D.

National Physical Laboratory, New Delhi 

Other Partners
Dr. Robert Cormack, Ph.D Brigham and Women's Hospital, Harvard Medical School, MA

Dr. Roy Tishler,M.D. Dana Farber Cancer Institute, Harvard Medical
Dr. Rajiv Kumar, Ph.D. Northeastern University
Dr. RenuPasricha, Ph.D. National Physical Laboratory, New Delhi 
Dr. Sukhvir Singh, Ph.D. National Physical Laboratory, New Delhi 
Dr. Premendra D. Dwivedi, Ph.D. Indian Institute of Toxicology Research, Lucknow
Dr. Rishi Shanker, Ph.D. Indian Institute of Toxicology Research, Lucknow
Dr. Suresh C. Sharma, M.B.B.S. All India Institute of Medical Sciences, New Delhi

PROJECT SUMMARY

Cancer is a leading cause of death in developed as well as in developing countries. Among various deadly cancers, the incidence of head and neck cancer (HNC) in the world is on rise. Among HNC, oral cavity cancer is the second most common in India and accounts for 86% of the world's oral cancer cases (National Institute of Public Health in February 2011). The appearance of 800,000 – 900,000 new cases every year poses an alarming threat worldwide. Modern modalities to treat HNC are radiation, chemotherapy, surgery, antibody-blocking therapy, or a combination of these therapies. In spite of technological developments, the available therapies for HNC suffer significant limitations. The presence of important organs such as carotid artery, eye, and brain in head and neck area hinders surgical resection. At the same time, the high failure rate and toxicity of radiotherapy limits its utility.

Docetaxel is a leading FDA approved chemotherapeutic for HNC. Leading clinicians at Dana Farber Cancer Institute and others have shown the efficacy of combining chemo- and radiation therapy, particularly taxanes like docetaxel. [1,2] However docetaxel which is administered systemically leads to severe systemic toxicity such as neutropenia. Furthermore the current systemic administration is highly inefficient with poor tumor accumulation and is bio-active only for a day or so. Accordingly there is a tremendous need for an approach that is highly efficient in delivery and the same time minimizes toxicity.

Here we propose to test an innovative sustained local drug release nanoplatform for HNC capable of locally radio-sensitizing the specific HNC malignant site and minimizing systemic toxicity and reducing the radiation dosage. The proposed design involves using poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with a model radiosensitizing drug Docetaxel (DTX) which will be administered intra-tumorally to provide localized in-situ delivery of the sensitizer to the tumor site. This will avoid the toxicity associated with current systemic delivery of radiosensitizers. The nanoplatform will improve the therapeutic ratio of radiation therapy without introducing additional patient interventions. This innovative approach is expected to results in new modalities in localized chemotherapy (LCT) and localized chemo-radiation therapy (LCRT).

PROJECT GOALS

The overall scientific goal for the project is to study the efficacy of LCT and LCRT using doctaxel-loaded nanoparticles through following specific aims

Specific Aim1: Fabrication and characterization of DTX- loaded PLGA nanoparticles (DTX-PLGA-NP) and in-vitro kinetic studies to optimize release kinetics.

Specific Aim2: In vivo time dependent intratumoral distribution profile using optical near infrared fluorescence imaging and therapeutic efficacy of LCT with the DTX-PLGA-NP administered intratumorally.

Specific Aim3: Studies of the efficacy of LCRT combining chemo- and radiation using DTX-PLGA-NP with brachytherapy I125 seeds.

Specific Aim4: Data analysis for planning the phase I clinical studies of the DTX-PLGA-NP System The proposed centre aims at applying novel concepts for improved HNC health management based on cutting-edge nanoscience & technology. Our mission is to facilitate collaborations between basic scientists, bioengineers and clinical investigators for speedily translating laboratory innovations to bedside for improved therapy, and health. The proposed center will act as a catalyst to bring together like-minded multidisciplinary team which will evolve via student and faculty exchange in the USA and India. This will have a great impact in improving our current knowledge and state of the art in nanomedicines to meet societal needs. This team will also explore mechanisms to secure external funding from different agencies and evolve a network of new partners in the two countries to achieve desired outcomes