NIR-II Light Leveraged Dual Drug Synthesis for Orthotopic Combination Therapy

Abstract

Pd-catalyzed bioorthogonal bond cleavage reactions are widely used and frequently reported. It is circumscribed by low reaction efficiency, which may encumber the therapeutic outcome when applied to physiological environments. Herein, an NIR-II light promoted integrated catalyst (CuS@PDA/Pd) (PDA - polydopamine) is designed to accelerate the reaction efficiency and achieve a dual bioorthogonal reaction for combination therapy. As NIR-II light can penetrate deeply into tissue, the Pd-mediated cleavage reaction can be promoted both in vitro and in vivo by the photothermal properties of CuS, beneficial to orthotopic 4T1 tumor treatment. In addition, CuS also catalyzes the synthesis of active resveratrol analogs by the CuAAC reaction. These simultaneously produced anticancer agents result in enhanced antitumor cytotoxicity in comparison to the single treatments. This is a fascinating study to devise an integrated catalyst boosted by NIR-II light for dual bioorthogonal catalysis, which may provide the impetus for efficient bioorthogonal combination therapy in vivo.

Photothermal Nanomaterials: A Powerful Light-to-Heat Converter

“…Since silica-cored Au nanoshells served as the first photothermal nanomaterials for clinical use, more and more inorganic agents with strong absorption in the NIR region, high chemical stability, adjustable water solubility, and minimal cytotoxicity have entered clinical trials. , Clinical trials have also been underway for small organic molecules due to their good biodegradability, good repeatability, and simple preparation. , Nevertheless, the major challenges for the clinical implementation of photothermal nanomaterials are the complex metabolism and excretion behaviors . The representative works on PTT with diverse photothermal nanomaterials in recent years − are summarized in Table .…”

“…The tumor growth is efficiently curbed with the inhibition rate of 97% and eliminated with no recurrence for 30 days. As a result, PTT and its combinational therapies with demonstrated efficacy have been well developed as promising treatment options for various life-threatening diseases. ,,− …”

Target‐Specific Bioorthogonal Reactions for Precise Biomedical Applications

“…developed the first light‐gated heterogeneous Pd‐based catalyst that could effectively control the bioorthogonal reactions in living cells [53] . In consideration of the shallow penetration of UV light, NIR‐I light and NIR‐II light promoted bioorthogonal catalysts have been devised [80,81] . The NIR light promoted bioorthogonal catalysis exhibited gratifying performance in prodrug activation for the treatment of solid tumors and orthotopic tumors in vivo.…”

“…As discussed in this minireview, ArMs provide a perspective to keep the metal catalytic site safe in their pockets and prevent poisoning by intracellular inhibitors [90] . What's more, it's a reasonable method to improve the catalytic efficiency of bioorthogonal catalysts by external stimuli, such as light and magnetic field induced ROS or heating [80,81,84] …”

Microfluidic Formulation of Curcumin-Loaded Multiresponsive Gelatin Nanoparticles for Anticancer Therapy

“…Cancer is a major disease that seriously affects human life and health. − At present, cancer treatment includes surgical resection, radiotherapy, and chemotherapy, and in recent years, gene therapy, , cell therapy, , photodynamic therapy, − and photothermal-ablation therapy. − Each method has its own pros and cons, and anticancer approaches combining two or more methodologies have been shown to be much more effective. , Therefore, therapeutic formulations combining multiple treatment methods are more promising for the future of anticancer therapies.…”