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, ELP(1), was designed to spontaneously undergo a soluble-insoluble phase transition (forming viscous microparticles) between room temperature and body temperature upon intratumoral injection, while ELP(2) 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-ELP(1) in the
tumor was significantly longer than the thermally insensitive ELP(2) conjugate. In addition, the thermal transition of ELP(1) significantly protected the conjugated
radionuclide from dehalogenation, whereas the conjugated
radionuclide on ELP(2) was quickly eliminated from the
tumor and cleaved from the
biopolymer. These attributes of the thermally sensitive ELP(1) depot improved the antitumor efficacy of
iodine-131 compared to the soluble ELP(2) 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.