Depot system for controlled release of gold nanoparticles with precise intratumoral placement by permanent brachytherapy seed implantation (PSI) techniques.
We report the design of a nanoparticle depot (NPD) system for local delivery of gold nanoparticles (AuNP) that facilitates their controlled release and is implantable into tumors by permanent seed implantation (PSI) brachytherapy techniques. Various sizes (5, 15, 30, and 50nm) of polyethylene glycol (PEG) coated AuNP and concentrations (6%, 8%, and 10% w/v) of calcium alginate used to form the NPD were studied. AuNP release rate, diffusion characteristics and spatial distribution were characterized in a tissue equivalent phantom model, and in a breast cancer tumor xenograft model and compared to a Fickian diffusion computational model, to identify the optimal NPD composition. In phantoms, 5nm and 15nm AuNP were released more rapidly than 30nm or 50nm AuNP but when implanted into tumor xenografts, AuNP exhibited slower release from NPD. Controlled prolonged release of AuNP was observed in tumor tissue over durations which were dependent on AuNP size. Maximum release and distribution in tumors were achieved using 5nm AuNP incorporated into the NPD. These results demonstrate the potential for the NPD as an effective local delivery system for AuNP-based therapies.
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Priscilla
P
Lai
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Eli
E
Lechtman
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Shahram
S
Mashouf
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, Erasmus MC, Rotterdam, The Netherlands. Electronic address: j.p.pignol@erasmusmc.nl.
Jean-Philippe
JP
Pignol
Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada; Joint Department of Medical Imaging and Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada. Electronic address: raymond.reilly@utoronto.ca.
Raymond M
RM
Reilly
D000818:Animals; D001918:Brachytherapy / Q000379:methods; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D016513:Mice, SCID; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
D003692:Delayed-Action Preparations; D011092:Polyethylene Glycols; D006046:Gold
Calcium alginate; Diffusion; Gold nanoparticles; Nanoparticle depot; Tissue-equivalent phantom; Tumor xenograft