title: Nanoparticle-based brachytherapy spacers for delivery of localized combined chemoradiation therapy.
abstract: OBJECTIVE
  In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits.
  
  
  METHODS
  Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues.
  
  
  RESULTS
  The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days.
  
  
  CONCLUSIONS
  The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy.
authors: Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. Electronic address: r.kumar@neu.edu.
authors: Rajiv
authors: R
authors: Kumar
authors: Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts.
authors: Jodi
authors: J
authors: Belz
authors: Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts.
authors: Stacey
authors: S
authors: Markovic
authors: Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts.
authors: Tej
authors: T
authors: Jadhav
authors: Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts.
authors: William
authors: W
authors: Fowle
authors: Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts.
authors: Mark
authors: M
authors: Niedre
authors: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
authors: Robert
authors: R
authors: Cormack
authors: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
authors: Mike G
authors: MG
authors: Makrigiorgos
authors: Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
authors: Srinivas
authors: S
authors: Sridhar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001918:Brachytherapy / Q000295:instrumentation* / Q000379:methods*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000295:instrumentation / Q000379:methods; D000077143:Docetaxel; D004343:Drug Implants / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D012822:Silicon Dioxide / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004343:Drug Implants; D053769:Nanocapsules; D043823:Taxoids; D000077143:Docetaxel; D012822:Silicon Dioxide
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