Hyperthermia-triggered UK release nanovectors for deep venous thrombosis therapy.

Deep vein thrombosis (DVT) is a common and lethal complication of surgery. In the clinic, thrombolytic drugs are primarily used for treating DVT. However, the utilization of thrombolytic drugs is limited due to the risk of urokinase (UK)-related hemorrhagic complications. In this paper, a binary eutectic phase-change fatty acid composed of lauric acid and stearic acid was used to block the pores of gold-mesoporous silica core-shell nanoparticles, so as to deliver thrombolytic drugs. The eutectic mixture has a well-defined melting point at 39.2 °C, which can be used as a biocompatible phase-change material for hyperthermia-triggered drug release. The prepared system presents remarkable photothermal effects due to the gold nanoparticles and quick drug release in response to near-infrared irradiation (NIR). In addition, localized hyperthermia could also enhance the lysis of the thrombus. The thrombolytic effect of this system was evaluated in vitro and in vivo. Herein, a rabbit femoral vein thrombosis model was first built for imitating thrombolysis in vivo. The B-ultrasound was then used to monitor the changes in the thrombus after treatment. The results indicated that the reported system could be potentially used to deliver thrombotic drugs in the clinic.

A magnetically modified black phosphorus nanosheet-based heparin delivery platform for preventing DVT accurately.

A new heparin targeting delivery platform was developed based on iron oxide (Fe3O4) nanoparticles and polyethyleneimine (PEI) functionalized black phosphorus nanosheets (BP NSs). Both in and ex vivo studies suggested that this drug delivery platform (PEI/Fe3O4@BP NSs) possessed high heparin loading capacity (≈450%), accurate magnetic enrichment capacity, and good biocompatibility. With the aid of near-infrared (NIR) laser irradiation, this BP NS based delivery platform could further enhance the photothermal thrombolysis effect. Most importantly, the experiments in vivo confirmed that the proposed PEI/Fe3O4@BP NSs could considerably prolong the effective drug concentration duration of heparin. By which means, accurate, long-acting, and effective thromboprophylaxis could be accomplished with limited drug dosage, which could radically reduce the perniciousness of drug overdose.

Localized Light-Au-Hyperthermia Treatment for Precise, Rapid, and Drug-Free Blood Clot Lysis.

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-Au-hyperthermia (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.