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UV emitting nanoparticles as novel radiation sensitizers targeting hypoxic cells

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA206645-01A1
Agency Tracking Number: R41CA206645
Amount: $299,992.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 102
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-04-03
Award End Date (Contract End Date): 2018-08-02
Small Business Information
44 HUNT ST
Watertown, MA 02472-4699
United States
DUNS: 073804411
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 MICHAEL SQUILLANTE
 (617) 668-6808
 msquillante@rmdinc.com
Business Contact
 KANAI SHAH
Phone: (617) 668-6853
Email: kshah@rmdinc.com
Research Institution
 RADIATION MONITORING DEVICES, INC.
 
44 HUNT ST
WATERTOWN, MA 02472-4624
United States

 Domestic nonprofit research organization
Abstract

Project Summary Abstract
Radiation therapy is one of the primary therapeutic techniques for treating cancer Nearly two thirds of
all cancer patients will receive radiation therapy during their illness with an average of radiation treatment
episodes Although largely effective radiation therapy like other forms of cancer treatment has difficulty
killing hypoxic regions within solid tumors
Cellular hypoxia is associated with radiotherapy resistance resulting in the incomplete killing of cancer
cells and leading to recurrence and relapse Thus developing techniques to target the hypoxic core of tumors
is a major goal of cancer research Nearly of all breast cancers and of locally advanced breast cancers
are hypoxic and their altered metabolism is strongly linked to resistance to radiotherapy and systemic therapy
In prostate cancer hypoxia is associated with early biochemical relapse after radiotherapy and also with local
recurrence in the prostate gland
A variety of approaches are being used to enhance the efficacy of radiation therapy and reduce dose
These include the use of nanoparticles to enhance the radiosensitization of tumor tissue reversing radiation
resistance in tumor tissue and increasing the radioresistance of healthy tissue
In this proposed effort we will develop a new technique that enhances radiation treatment by using a
sensitizer that both increases the energy deposited locally within the tumor and generates UV photons in the
vicinity of the DNA in cancer cells Our sensitizer consists of scintillating nanoparticles that emit UV radiation
capable of both directly damaging the DNA in hypoxic cancer cells In addition these particles will be
composed of high atomic number elements with much higher radiation stopping power than the low atomic
number elements that make up tissue This will enhance the efficacy of the high energy X rays used in
radiation treatment by down converting the X ray photon energy into lower energy X rays and particles which
have a much higher energy deposition rate linear energy transfer LET We have performed a preliminary
experiment which gave encouraging results showing an increase in cell death using the LuPO scintillating
nanoparticles
In Phase I of this effort we will model photon transport and energy conversion for both X rays and UV
photons and experimentally demonstrate the effectiveness of the concept in vitro In Phase II we will develop
size homogenous nanoparticles suitable for use in exhaustive in vitro cell experiments and preclinical studies Project Narrative
This project will investigate enhancing the efficacy of radiation treatment of cancer by using scintillating
nanoparticle sensitizers that emit UV photons This sensitizer will enhance the treatment in two ways first by
generating UV photons in the immediate vicinity of cancer cells which can interact directly with its DNA to
cause lethal damage in an oxygen independent way and second by making more efficient use of the X ray
energy that strikes the tumor cell by generating softer more tissue absorbent x rays and photoelectrons The
end result will be UV generating nanoparticles with a higher efficacy in the treatment of resistant hypoxic cells
of the tumor filling an important unmet clinical need

* Information listed above is at the time of submission. *

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