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Collagen Hybrid Peptides and Facilitators in Targeting-Free Cell Selection and Uptake of Maliganant Cells

Award Number: SC3GM099594
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2012
PERIOD OF PERFORMANCE END DATE: 04/30/2023

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Collagen Hybrid Peptides and Facilitators in Targeting-Free Cell Selection and Uptake of Maliganant Cells - Summary Cancer is the second leading cause of death in the United States. Many of the cancer drugs exhibit systemic and non-selective toxicity to all tissues. To limit systemic toxicity of cancer drugs, chemical and biological targeting has been proposed. In targeted approaches, the drugs are delivered to a specific location (i.e. only cancer cells) using targeting moieties, such as antibodies, aptamers, small protein scaffolds, peptides, and small molecule ligands. Currently, targeted methods are in clinical use and under investigation; however, success has been limited. The goal of this proposal is to develop a new, generic, targeting-free drug delivery method for localized cancer that in the future can result in more effective and less toxic treatments than current methodologies. Our approach relies on cell selection process controlled by externally induced temperature difference between the targeted cells and the adjacent cells. Drug delivery is facilitated by a peptide-based drug carrier, specifically designed to fold into triple helical conformation at temperatures lower than 37C and penetrate cellular membrane only when folded. Thus, when in a coiled, non-helical conformation (above 37C), the peptide cannot be internalized by the cells (OFF switch). When the temperature is lower than the folding temperature, the peptide will undergo coil-to-helix transition and assemble into triple helix. The peptide in the helical conformation can be internalized by the cell (ON switch). In addition we propose to develop cooling device that can externally-induce temperature difference between the targeted cells and the adjacent cells to assist with the temperature-responsive peptide nanocarrier uptake to malignant cells. This proposal aims to establish thermal discrimination conditions of nanocarrier delivery to selected cancer cells (MCF-7, A495, FaDu), determine peptide nanocarrier folding kinetics and correlate it with cellular uptake. This aim will be accomplished using Circular Dichroism (CD) spectroscopy and the flow chamber equipped with syringe pump to mimic conditions in vivo. In addition, we aim to design and test cooling device to locally control temperature gradient to assist the delivery. The developmental objective is to increase the PI's involvement in interdisciplinary research directly related to human health and to increase the productivity of the PI laboratory. The requested support will result in the development of new methodologies and protocols that incorporate many scientific fields, including synthetic chemistry, cell biology, and engineering. This will directly increase participation of graduate (MS) and undergraduate students, including students from traditionally underrepresented backgrounds. This SC3 support, if awarded, will increase the PI's research output and improve competitiveness for major grant support such as NSF and NIH-RO1 type grants.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	CALIFORNIA STATE UNIVERSITY LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	12/5/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $110,625 )
2021	2021	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	4/19/2021	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2020 ( Subtotal = $110,625 )
2020	2020	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	7	4/7/2020	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2019 ( Subtotal = $110,625 )
2019	2019	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	6	5/21/2019	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2018 ( Subtotal = $110,625 )
2018	2018	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	5	4/25/2018	COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2015	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	7/17/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $108,375 )
2015	2015	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	6/10/2015	NON-COMPETING CONTINUATION	$108,375
														Subtotal = $108,375

Issue Date FY: 2014 ( Subtotal = $108,375 )
2014	2014	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	3/31/2014	NON-COMPETING CONTINUATION	$108,375
														Subtotal = $108,375

Issue Date FY: 2013 ( Subtotal = $104,582 )
2013	2013	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	3/12/2013	NON-COMPETING CONTINUATION	$97,538
2013	2013	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	2	6/14/2013	NON-COMPETING CONTINUATION	$7,044
														Subtotal = $104,582

Issue Date FY: 2012 ( Subtotal = $108,375 )
2012	2012	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	3/23/2012	NEW	$108,375
														Subtotal = $108,375

Grand Total All Awards = $872,207

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Collagen Hybrid Peptides and Facilitators in Targeting-Free Cell Selection and Uptake of Maliganant Cells

Award Number: SC3GM099594

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2012

PERIOD OF PERFORMANCE END DATE: 04/30/2023

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