简介: |
Abstract: Intratumoral administration of radionuclides (radionuclide therapy) has the potential to deliver the maximum amount of radioactivity to the tumor and can spare surrounding tissues from harmful side effects. All the radionuclides, however, are unable to capitalize on this effect because they are rapidly cleared from the tumor following injection due to their low molecular weight. Elastin-like polypeptides (ELP) are a class of genetically engineered polymers that undergo an inverse temperature phase transition; they are soluble at the temperatures below their characteristic transition temperature (Tt), and form insoluble aggregates above their Tt. Using this ELP, we developed a versatile, genetically engineered peptide polymer as a “smart” radionuclide carrier that displays potent antitumor efficacy by rationally tailoring intratumoral retention time through the modulation of its phase transition behavior. The therapeutic efficacy herein reported, which led to 100% response rates in two human tumor xenograft models and greater than 67% of complete tumor regression until the completion of the experiment (i.e., 60 days), is in stark contrast with the efficacy observed on our seminal work with radiolabeled ELPs. This radiotherapy modality showed very minimal systemic toxicity in mice. These data indicate the in situ self-assembly of biodegradable and injectable radionuclide “seed” is a promising therapeutic alternative to conventional brachytherapy.
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