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 (Hf) 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 Tc, 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 Tc-Hf-TCPP-PEG NCPs, could endow nontherapeuticTc with the therapeutic function of killing cancer cells, likely owing to the interaction of Hf with γ rays emitted from Tc to produce charged particles for radiosensitization. With efficient tumor retention, as revealed by SPECT imaging, ourTc-Hf-TCPP-PEG NCPs offer exceptional therapeutic results in eliminating tumors with moderate doses of Tc 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 withTc, a short-half-life (6.0 h) diagnostic radioisotope, which is promising for cancer RIT with enhanced efficacy and reduced side effects.

Porphyrin MOF Dots–Based, Function‐Adaptive Nanoplatform for Enhanced Penetration and Photodynamic Eradication of Bacterial Biofilms

“…The strategy for the synthesis of the function‐adaptive MMNPs was shown in Scheme A. Hf (IV)‐based porphyrin MOFs were first synthesized by a simple solvothermal method according to previous studies . Then a facile ultrasonication treatment was employed to prepare the ultrasmall‐sized pMOF dots.…”

Design of Targeted Nanostructured Coordination Polymers (NCPs) for Cancer Therapy

“…The use of NCPs has opened new avenues in the design of new therapeutic tools and strategies to treat many cancers. Different new approximations try to solve problems related to the physiology of tumor extracellular matrix (ECM) to improve the tumor retention and penetration of therapeutic agents [92], the use of NCPs as biocompatible gene-regulation agents [93], obtaining of active nanoparticles in radioisotope therapy (RIT) for clinical cancer treatment [94], or the encapsulation of individual tumor cells in biocompatible coordination polymers, as whole cell vaccines, to regulate the immune system and combat metastatic cancer [95]. All these very recent examples prelude an intense and prolific research field that make us think that the clinical use of these nano-systems is likely not so far.…”

Advances of functional nanomaterials for cancer immunotherapeutic applications

“…There were NPs composed of hafnium (Hf 4+ ) and tetrakis (4‐carboxyphenyl) porphyrin that could carry radioactive labels developed by Yu et al labeled with 99m Tc 4+ , the NPs could be used for single‐photon emission computed tomography (SPECT) in clinical. Meanwhile, Hf showed endowing 99m Tc with the function of killing cancer cells, which heralded the potential of this material in immunotherapy combined with radiotherapy (Chao, Liang, et al, ).…”