Highly Effective Radioisotope Cancer Therapy with a Non-Therapeutic Isotope Delivered and Sensitized by Nanoscale Coordination Polymers.

Abstract

Nuclear medicine with radioisotopes is extremely useful for clinical cancer diagnosis, prognosis, and treatment. Herein, polyethylene glycol (PEG)-modified nanoscale coordination polymers (NCPs) composed of hafnium (Hf⁴⁺) and tetrakis (4-carboxyphenyl) porphyrin (TCPP) are prepared via a one-pot reaction. By chelation with the porphyrin structure of TCPP, such Hf-TCPP-PEG NCPs could be easily labeled with ^99mTc⁴⁺, an imaging radioisotope widely used for single-photon emission computed tomography (SPECT) in a clinical environment. Interestingly, Hf, as a high- Z element in such ^99mTc-Hf-TCPP-PEG NCPs, could endow nontherapeutic ^99mTc with the therapeutic function of killing cancer cells, likely owing to the interaction of Hf with γ rays emitted from ^99mTc to produce charged particles for radiosensitization. With efficient tumor retention, as revealed by SPECT imaging, our ^99mTc-Hf-TCPP-PEG NCPs offer exceptional therapeutic results in eliminating tumors with moderate doses of ^99mTc after either local or systemic administration. Importantly, those biodegradable NCPs could be rapidly excreted without much long-term body retention. Our work, showing the success of applying NCPs for radioisotope therapy (RIT), presents a potential concept for the realization of highly effective cancer treatment with ^99mTc, a short-half-life (6.0 h) diagnostic radioisotope, which is promising for cancer RIT with enhanced efficacy and reduced side effects.