title: Brachytherapy using injectable seeds that are self-assembled from genetically encoded polypeptides in situ.
abstract: Brachytherapy is a common clinical technique involving implantation of sealed radioactive "seeds" within a tumor to selectively irradiate the tumor mass while minimizing systemic toxicity. To mitigate the disadvantages associated with complex surgical implantation and subsequent device removal procedures, we have developed an alternative approach using a genetically encoded peptide polymer solution composed of a thermally responsive elastin-like polypeptide (ELP) radiolabeled with (131)I that self-assembles into radionuclide seeds upon intratumoral injection. The formation of these nontoxic and biodegradable polymer seeds led to prolonged intratumoral retention (~85% ID/tumor 7 days postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor-bearing animals after a single administration of labeled ELP. These results suggest that in situ self-assembly of biodegradable and injectable radionuclide-containing polypeptide seeds could be a promising therapeutic alternative to conventional brachytherapy.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA. wengeliu@duke.edu
authors.forename: Wenge
authors.initials: W
authors.lastname: Liu
authors.forename: Jonathan
authors.initials: J
authors.lastname: McDaniel
authors.forename: Xinghai
authors.initials: X
authors.lastname: Li
authors.forename: Daisuke
authors.initials: D
authors.lastname: Asai
authors.forename: Felipe Garcia
authors.initials: FG
authors.lastname: Quiroz
authors.forename: Jeffery
authors.initials: J
authors.lastname: Schaal
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Park
authors.forename: Michael
authors.initials: M
authors.lastname: Zalutsky
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D000818:Animals; D001918:Brachytherapy / Q000379:methods*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004549:Elastin / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D020080:Tandem Repeat Sequences; D023041:Xenograft Model Antitumor Assays
chemical_list: D007457:Iodine Radioisotopes; D010455:Peptides; D004549:Elastin