Currently, most thrombolytic agents are limited by short circulation time and excessive dose needed for clinical therapy, which increases lethal risk for intracranial hemorrhage. Here, a near-infrared-triggered, controlledrelease system, using gold@mesoporous silica core-shell nanospheres (Au@MSNs) with phase-changed material 1-tetradecanol, is formulated to release urokinase plasminogen activators (uPA) on demand. The prepared system presents a sensitive system for releasing uPA, owing to an elevated temperature created by Au@MSNs-induced photothermal effect. For in vitro study, a 3D printed vein vasculature is designed and fabricated to simulate the thrombolysis of system in blood vessel. Murine tail thrombus model is also built to evaluate thrombolysis in vivo. Consequently, localized hyperthermia is validated to possess an effective enhancement for thrombolysis. Therefore, according to the results, the fabricated system demonstrates two aspects of potential superiority: controlled uPA release for reducing risk of side effects, and hyperthermia-enhanced thrombolysis locally for decreasing drug dosage. Assisted with thermal thrombolysis, the present formulated system shows a high efficiency, on-demand drug release, and thus a safer protocol for thrombolytic therapy, which fits the developing trends of precision medicine.
Purpose: The frequent usage of various lighting screens has made dry eye syndrome an increasingly serious phenomenon. To relieve this global problem, we have developed a photothermal conversion hydrogel based mini-eye patch. Methods: Gold nanoparticles (GNRs) were synthesized by a seed-mediated method, and then used as the inner cores to grow palladium (Pd) shell by PdCl42-reduction. Then, gelatin was added to prepare GNRs @ Pd hydrogel eye patch by genipin cross-linking. We implanted temperature sensitive ink (complex composed of amino resin and styrene maleic anhydride copolymer) in the eye patch, which could change color at different temperatures. Heating performance of the eye patch was accessed with an infrared temperature profile and the circulating temperature experiment. The safety assessment of the eye patch was conducted by H&E staining of the mouse’s eyelid skin and CCK-8 assay. A Keratograph 5M noninvasive ocular surface analyzer was used to assess the impact of eye patches on dry eyes. Results: It was found that GNRs @ Pd hydrogel eye patches could sense various visible light and responded by heating up spontaneously. Results from the CCK-8 assay and H&E staining showed that the eye patch has good safety performance. Measurements of the first noninvasive tear break-up time (NITBUT), the average NITBUT, the tear meniscus height (TMH), combined with red eye analysis, further demonstrated the patch’s eye-protective properties. Conclusion: After being pasted to the lacrimal gland, the hydrogel patch converted various light irradiations into heat and stimulated the lacrimal gland to produce more tears to relieve dry eye. The built-in temperature-sensitive ink can play an important role in warning people of their excessive eye usage. Because this recyclable strategy does not interfere with normal eye use, it is thus more environmentally friendly and convenient than ordinary infrared eyewear.
With the inspiration of the shape of the loquat fruit, here, we developed a similarly shaped Janus carrier. This peculiar gold rod-partially exposed structure not only significantly increased the drug loading capability but also improved its infrared response efficiency. A better effect of drug-photothermal treatment thus could be realized. With the aid of an external 3D printed drug guiding device, this carrier could accurately reach different affected areas. The subsequent infrared triggered multiple tumor therapy, thus, could be conducted in the designated location. The corresponding experimental results demonstrated the reliability, flexibility, and biocompatibility of the proposed drug delivery system for two different tumor targeting treatments.
Thrombus diseases, induced by blood stasis or vascular embolization normally, frequently occur with high disability and mortalities worldwide. At present, drug thrombolysis, a primary clinical therapy for blood clot lysis, could increase the lethal risk for hemorrhage when thrombolysis agents are overused in the whole body. Therefore, a novel and advanced therapy for blood clot lysis, based on remote physical signals, is helpful for assisting clinical therapy. Here, we used the localized light-Auhyperthermia (LAH) treatment, induced by gold nanorods (Au NRs) irradiated with near-infrared light (808 nm), for precise, rapid, and drug-free blood clot lysis. The LAH technology was first introduced in the murine hematoma model and the murine myocardial infarction model for blood clot lysis. Compared with traditional therapy, LAH was assured to shorten the time of detumescence in the murine hematoma model owing to their precise and localized hyperthermia. Meanwhile, we also discovered that LAH was a benefit to vascular recanalization in the murine myocardial infarction model. In addition, the Au NRs used in LAH present ideal biocompatibility in the murine model, which endows it to be suitable for blood clot lysis in vivo.
At present, the clinical treatment of malignant glioma is still unsatisfactory. The existence of the blood–brain barrier hinders most chemical and biological drugs to reach the brain tissue. In this study, a square‐shaped Janus drug carrying system, which incorporated with high infrared responsiveness, large drug loading capacity, and reliable magnetic targeting capabilities is synthesized. Combined with an external 3D printed magnetic wearable equipment, this carrying system can effectively penetrate the blood–brain barrier in both in vitro and in vivo tests, it is thus applied to two different targeting tumor therapies (including glioma). Animal experiments demonstrate the multiple therapeutic effects of the proposed system. The subsequent studies imply that the obtained carrier has no obvious toxic effects on the organs of animals. Different from the classical biochemical targeting method, this study uniquely combines the porous Janus nanocarrier with an external wearable magnetic guidance device (physical targeting), which is a promising target therapeutic concept with impressive flexibility and reliability.
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