Near-infrared photocontrolled release of Nitric oxide nanoprobe for gas /photothermal /radionuclide multimodal therapy in differentiated thyroid carcinoma.

Introduction: There is no standard therapy for radioiodine-refractory differentiated thyroid cancer which do not respond to tradi-tional therapies. It is urgently needed to develop a safe and effective strategy for radioiodine-refractory and surgically inoperable thyroid cancer. While high concentration of Nitric Oxide (NO) can induce cancer cell apoptosis, its half-life in vivo is relatively short and unstable. With the rapid development of nanobiotechnology, the NO donors based on nanomaterials has been becoming an emerging direction. In this work, a new type of near-infrared photocontrolled release of nitric oxide (NO) nanoprobe was designed and labeled with radionuclide ¹³¹I to achieve gas / photothermal / radionuclide multimodal therapy in differentiated thyroid carcinoma.

Methods: We designed and synthesized the NIR-controlled release of NO donor (LN-NO). In addition, polydopamine nanoparticles(PDA)were synthesized by self-polymerization of Dopamine Hydrochloride(DA) and modified with Polyethylene glycol(PEG). Using the excellent surface modification ability of polydopamine nanoparticles, a multifunctional drug delivery system was designed by loading radionuclide ¹³¹I and NO donors. Finally, it was used in the combined therapy for thyroid carcinoma-bearing mice.

Results: PEG-PDA nanoparticles can be efficiently loaded with NO donors and radionuclide ¹³¹I. Nitric Oxide nanoparticles labeled with ¹³¹I (¹³¹I-LN-NO@PEG -PDA) can achieve controlled on-demand release of NO under near-infrared light. The results of cell experiment in vitro displayed that the nanodelivery system had good uptake ability and no obvious cytotoxic side effects. In vivo experiments in mice, it had long blood circulation and high tumor enrichment ability, can quickly and stably remain in tumor cells, showing obvious tumor killing effect. Compared with the simple therapeutic effect, the combined treatment significantly inhibited the growth of tumor in mice, showing obvious advantages.

Conclusions: In this study, a poly-dopamine (PDA) multifunctional drug delivery system modified by polyethylene glycol (PEG) was proposed and obtained, which can combine radionuclide ¹³¹I with NO donor. Under near-infrared irradiation, PEG-PDA nanoparticles generate a large amount of heat for photothermal therapy on the one hand, and transfer the generated energy to NO donor and realize photocontrolled release of NO on the other hand. The most important thing is that due to the existence of the nano-carrier, it can achieve the passive targeted aggregation of ¹³¹I, reducing the radiation damage at the normal site, and achieving the purpose of gas / photothermal / radionuclide multimodal treatment of tumor.Therefore, we hope that the new nano-probe can provide a valuable reference for tumor treatment in the future.

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