|Title||Injectable intratumoral depot of thermally responsive polypeptide–radionuclide conjugates delays tumor progression in a mouse model|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Liu, W, MacKay, JA, Dreher, MR, Chen, M, McDaniel, JR, Simnick, AJ, Callahan, DJ, Zalutsky, MR, Chilkoti, A|
|Journal||Journal of Controlled Release|
|Pagination||2 - 9|
This study evaluated a biodegradable drug delivery system for local cancer radiotherapy consisting of a thermally sensitive elastin-like polypeptide (ELP) conjugated to a therapeutic radionuclide. Two ELPs (49 kDa) were synthesized using genetic engineering to test the hypothesis that injectable biopolymeric depots can retain radionuclides locally and reduce the growth of tumors. A thermally sensitive polypeptide, ELP1, was designed to spontaneously undergo a soluble–insoluble phase transition (forming viscous microparticles) between room temperature and body temperature upon intratumoral injection, while ELP2 was designed to remain soluble upon injection and to serve as a negative control for the effect of aggregate assembly. After intratumoral administration of radionuclide conjugates of ELPs into implanted tumor xenografts in nude mice, their retention within the tumor, spatio-temporal distribution, and therapeutic effect were quantified. The residence time of the radionuclide–ELP1 in the tumor was significantly longer than the thermally insensitive ELP2 conjugate. In addition, the thermal transition of ELP1 significantly protected the conjugated radionuclide from dehalogenation, whereas the conjugated radionuclide on ELP2 was quickly eliminated from the tumor and cleaved from the biopolymer. These attributes of the thermally sensitive ELP1 depot improved the antitumor efficacy of iodine-131 compared to the soluble ELP2 control. This novel injectable and biodegradable depot has the potential to control advanced-stage cancers by reducing the bulk of inoperable tumors, enabling surgical removal of de-bulked tumors, and preserving healthy tissues.
|Short Title||Journal of Controlled Release|