R01CA257241

Rational Translation of Gold Nanoparticle Mediated Radiosensitization to the Clinic

The use of high atomic number (Z) elements as radiosensitizers of tumors has been well documented in the literature over the last few decades. In particular, gold nanoparticles (GNPs), typically defined as high-Z gold structures with the longest dimension smaller than 100 nm, have been the subject of active investigation for the same purpose for the past 15 years.

Early in vivo demonstration of GNP-mediated radiosensitization (GMR) effect was based on passive accumulation of GNPs within tumors ("passive targeting"). While resulting in a remarkable level of GMR, this approach generally requires clinically less relevant radiation quality (low energy kilovoltage X-rays) and clinically unachievable (without direct injection) gold concentration (up to 7mg gold per gram of tumor).

To overcome these difficulties, we have been investigating an alternative approach based on "active targeting" which shows a promising outlook for clinical translation in the near term. This proposal seeks to surmount the remaining challenges associated with our active targeting-based approach before embarking on clinical translation of GMR.

Specifically, we aim to identify the molecular mechanism of GMR, biodistribution and kinetics of GNPs developed for clinical translation, their fate at the tumor and cellular levels, and the correlation between GNP-mediated dose enhancement and GMR. Despite abundant data and publications on GMR accumulated over the years, critical knowledge gaps still exist in terms of the aforementioned aspects, hindering clinical translation of GMR.

As demonstrated in our preliminary data, we propose to address such issues that hold the key for clinical translation of GMR, through concerted multidisciplinary efforts. Upon achieving this goal, a pilot human trial of GNP-enhanced radiation therapy (RT) will also be conducted within this project for the management of recurrent rectal cancer.

Overall, we will pursue three specific aims shown below to achieve the goals of this project:

1. To determine the molecular mechanism of GMR, the biodistribution/kinetics of GNPs in vitro and in vivo, and the radiosensitization efficacy in clinically relevant treatment scenarios.
2. To correlate GNP-mediated dose enhancement and GMR using high-resolution image-based cell/tissue models and nanoscale computational techniques.
3. To conduct a pilot human trial of GNP-enhanced RT for previously radiated recurrent rectal cancers.

Ultimately, this project would lay the foundation for widespread applications of the currently envisioned RT paradigm that enables more potent and tumor-specific RT with less toxicity.

University Of Texas Health Science Center At Houston

TO DEVELOP THE MEANS TO CURE AS MANY CANCER PATIENTS AS POSSIBLE AND TO CONTROL THE DISEASE IN THOSE PATIENTS WHO ARE NOT CURED. CANCER TREATMENT RESEARCH INCLUDES THE DEVELOPMENT AND EVALUATION OF IMPROVED METHODS OF CANCER TREATMENT THROUGH THE SUPPORT AND PERFORMANCE OF BOTH FUNDAMENTAL AND APPLIED LABORATORY AND CLINICAL RESEARCH. RESEARCH IS SUPPORTED IN THE DISCOVERY, DEVELOPMENT, AND CLINICAL TESTING OF ALL MODES OF THERAPY INCLUDING: SURGERY, RADIOTHERAPY, CHEMOTHERAPY, AND BIOLOGICAL THERAPY INCLUDING MOLECULARLY TARGETED THERAPIES, BOTH INDIVIDUALLY AND IN COMBINATION. IN ADDITION, RESEARCH IS CARRIED OUT IN AREAS OF NUTRITIONAL SUPPORT, STEM CELL AND BONE MARROW TRANSPLANTATION, IMAGE GUIDED THERAPIES AND STUDIES TO REDUCE TOXICITY OF CYTOTOXIC THERAPIES, AND OTHER METHODS OF SUPPORTIVE CARE THAT MAY SUPPLEMENT AND ENHANCE PRIMARY TREATMENT. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.395 - Cancer Treatment Research

National Cancer Institute (NCI) [HHS - NIH]

Houston, Texas 770303870 United States

Single Zip Code

Bioengineering Research Grants (BRG) (R01 Clinical Trial Required) (PAR-19-159)

Amendment Since initial award the End Date has been extended from 12/31/25 to 12/31/26 and the total obligations have increased 381% from $631,688 to $3,036,732.