Development of an Injectable Brachytherapy Using Self-Assembly Polypeptides

Brachytherapy has been recognized as efficient treatment for solid tumor due to reaching high radioactivity at injection site while minimizing systemic toxicity, but is not ideal because it leaves undegradable seeds in organ after treatment and has a complicated procedure for implantation. Here, we report an alternative modality that is injectable, biocompatible, and degradable and comprised of a thermally responsive, radiolabeled elastin-like polypeptide (ELPs), which promotes intratumoral retention and achieves complete tumor remission following intratumoral (i.t.) administration of iodione-131 labeled ELP-depot. ELPs are a genetically engineered class of peptide polymers that undergo an inverse temperature phase transition in water: they are soluble at a temperature below the transition temperature (Tt) but immediately aggregate when heated above the Tt. This Tt is tunable by adjusting the amino acid composition of the ELP, its molecular weight and solution concentration. For i.t. drug delivery, the ELP’s Tt was designed to exceed room temperature, while remaining below body temperature. This ensures that ELP aggregation occurs immediately after direct tumor infusion so as to retain the radionuclide specifically in the tumor and achieve high antitumor efficacy. The study results showed that the formation of these non-toxic and biodegradable polymer seeds led to prolonged intratumoral retention--->55% of the injected ELP retained in the tumor after 31 days. After optimizing the ELP molecular and injection formula design and evaluation, this ELP-radionuclide (131I) depot after single i.t. injection demonstrates marked antitumor efficacy in both subcutaneous and orthotopic xenograft tumors in mice with >67% of tumors having complete remissions and showed only minimal accumulation (<1% ID/g) in vital organs. 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.