A mitochondria-targeted molecular phototheranostic platform for NIR-II imaging-guided synergistic photothermal/photodynamic/immune therapy

Abstract

Phototherapy is a conducive and non-invasive strategy for cancer therapy under light irradiation. Inspiringly, fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) holds a great promise for imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. However, most phototherapeutics still face great challenges, including complicated synthesis of agents, potential biotoxicity and unsatisfied therapeutic outcomes. Herein, a near-infrared laser triggered molecular photosensitizer FEPT, modified with triphenylphosphine PEGylation (PEG2000-TPP), is developed for NIR-II imaging-guided mitochondria-targeting synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/immune therapy (IMT). The mitochondria-targeting photosensitizer FEPT can produce reactive oxygen species (ROS) and hyperpyrexia upon 808 nm laser irradiation, resulting in mitochondrial dysfunction and photo-induced apoptosis via caspase-3 pathway. Phototherapy-induced hyperthermia or ROS triggers the release of immunogenic intracellular substrates from dying tumor cells, thereby promoting the activation of antitumor immunity. Herein, this work provides a practicable strategy to develop a molecular phototheranostic platform for imaging-guided cancer therapy via mitochondria-targeting. Graphical Abstract

Mitochondrial‐Targeted CS@KET/P780 Nanoplatform for Site‐Specific Delivery and High‐Efficiency Cancer Immunotherapy in Hepatocellular Carcinoma

“…In the second step, the synthesis routes for P780 are presented in Figure S2A, Supporting Information. As shown in Figure S2B-D, Supporting Information the results of 1 H NMR, 13 C NMR, and HR-MS verified the successful synthesis of P780 molecules.…”

“…Following the removal of DMF, column chromatography was used to purify the crude product using methylene chloride and methanol as eluents. The structures of the products in step 1 and step 2 were analyzed by UV-vis spectrophotometry, 1 H NMR, 13 C NMR and HR-MS. Synthesis and Characterization of CS@KET/P780 NPs: KET (1 mg) and P780 (1 mg) were separately dissolved in methanol (MeOH, 100 μL), and the two were mixed thoroughly by ultrasound. The prepared mixture was slowly poured into 2 mL of deionized water containing CS while being stirred at 1000 rpm.…”

Oxidative stress induced by berberine-based mitochondria-targeted low temperature photothermal therapy

“…It is well known that PTT utilizing near-infrared (NIR) laser irradiation converts light energy into heat energy through photothermal agents, which locally generates high temperatures to induce thermal ablation of tumor cells ( Fan et al, 2022 ; Tunçel and Yurt, 2022 ; Zhong et al, 2022 ). Nevertheless, the thermal ablation during PTT might cause unwanted damages to the surrounding healthy tissues ( Yang S. et al, 2022 ). Recently, low-temperature PTT (LPTT) has been proposed to circumvent the above mentioned limitation at temperatures that are safe for the human body ( Ma et al, 2022 ).…”

A rationally engineered specific near-infrared fluorogenic substrate of human pancreatic lipase for functional imaging and inhibitor screening

“…Basically, near-infrared (NIR) substrates produce fluorescent products with long wavelength emission, minimizing tissue background fluorescence and light scattering, thereby offering strong tissue penetration and anti-interference, and improving the accuracy of detection of target enzyme activity. 36,37 Herein, we describe a novel highly specific and strong anti-interference fluorogenic substrate via a sequential screening strategy. The NIR fluorophore 7-HTCFC was first screened using a virtual docking technique, and its acyl side chain was further optimized to enhance the selectivity and fluorescence response to hPL.…”