Program Information
Novel PH Low Insertion Peptide and PEG Polymer Coated Gold Nanoparticles for Radiation Enhancement and Hyperthermia
T Crawford*, J Daniels , Y Reshetnyak , O Andreev , University of Rhode Island
Presentations
SU-F-205-5 (Sunday, July 30, 2017) 2:05 PM - 3:00 PM Room: 205
Purpose: Gold is an efficient absorber of x-rays to generate Auger electrons in the close vicinity of nanoparticles (tens of nm). Also, gold nanoparticles can absorb near infrared light (depending on nanoparticle size and shape), inducing surface plasmon-polaritons, which relax and transfer energy into heat. We introduced a novel method of synthesis of spherical and multispiked gold nanoparticles coated with polyethylene glycol (PEG) and the tumor-targeting pH-low insertion peptide (pHLIP) for potential use in radioenhancement and radiothermal therapy.
Methods: Spherical gold nanoparticles were synthesized using mixture of sodium citrate, PEG and pHLIP as a reducer. Multispiked particles were created using disk-like bicelles as a soft template, and mixture of ascorbic acid, PEG and pHLIP.
Results: The optimal conditions including time, temperature and ratios of sodium citrate or ascorbic acid, bicelles (for multispiked particles), PEG and pHLIP were established to introduce spherical and multispiked gold nanoparticles with a metal core diameter of about 7.0±2.5 nm and 146.0±50.4 nm, respectively. The stability and optical resonance of nanoparticles were investigated. The multispiked nanoparticle solution showed a concentration-dependent increase in temperature of up to 13°C as a result of 805 nm laser irradiation. Spherical gold nanoparticles exhibited pH-dependent cellular uptake and targeting of cancer cells (leaving muscle tissue unstained) within tumors. The intra-tumoral injection of spherical gold nanoparticles resulted in the retention of up to 30% ID/g of gold accumulation in the tumor.
Conclusion: The presence of pHLIP/PEG in the coating of nanoparticles resulted in increased stability and the promotion of low pH cellular uptake. The spherical particles have potential clinical applications as a close-range radiosensitizer that selectively targets the low pH extracellular environment of cancer cells within tumors. The multispiked particles could have applications in targeting the tumor mass in thermal therapies, increasing the temperature, and therefore the damage, in a localized area.
Funding Support, Disclosures, and Conflict of Interest: Oleg A. Andreev and Yana K. Reshetnyak have founded and have a financial interest in a company, pHLIP, Inc., with the aim of bringing pHLIP technology to the clinic. The company had no involvement in funding the studies.
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