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

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.