Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

Doxorubicin-loaded Prussian Blue-based nanoparticles for combined photothermal/chemotherapy against hepatocellular carcinoma.

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The cardiac effects of exercise preconditioning (EP) are well established; however, the mechanisms involving cardiac ATP-sensitive potassium channel (K channel) subunits and autophagy are yet to be fully established. The present work aims to investigate the alterations of cardiac K channel subunits Kir6.2, SUR2A, and autophagy-related LC3 during the late cardioprotective phase of EP against exhaustive exercise-induced myocardial injury. Rats run on treadmill for four running time intervals, each with 10 minutes running and rest. Exhaustive exercise was performed 24 h after EP. Cardiac biomarkers, cTnI and NT-proBNP, along with the histological stain, were served as indicators of myocardial injury. Cardiac K channel subunits Kir6.2 and SUR2A were analyzed in this study, and autophagy was evaluated by LC3. The results revealed that EP reduced the exhaustive exercise-induced high level of serum cTnI and myocardial ischemia/hypoxia; however, it did not reveal any changes in the serum NT-proBNP level or cardiac BNP. Cardiac SUR2A mRNA significantly upregulated during the exhaustive exercise. The high levels of Kir6.2, SUR2A, LC3IIpuncta and LC3II turnover observed after exhaustive exercise were significantly mitigated by EP in the late phase. These results suggest that EP alleviates myocardial injury induced by exhaustive exercise through the downregulation of cardiac K channels and autophagy.

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BackgroundBladder transitional cell carcinoma greatly threatens human health all over the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows a strong apoptosis-inducing effect on a variety of cancer cells including bladder cancer. However, adenovirus-mediated TRAIL expression still showed cytotoxicity to normal cells mainly due to lack of tumor specificity.MethodsTo solve the problem, we applied miRNA response elements (MREs) of miR-1, miR-133 and miR-218 to confer TRAIL expression with specificity to bladder cancer cells.ResultsExpression of miR-1, miR-133 and miR-218 was greatly decreased in bladder cancer than normal bladder tissue. Luciferase assay showed that application of the 3 MREs was able to restrain exogenous gene expression to within bladder cancer cells. Subsequently, we constructed a recombinant adenovirus with TRAIL expression regulated by MREs of miR-1, miR-133 and miR-218, namely Ad-TRAIL-MRE-1-133-218. qPCR, immunoblotting and ELISA assays demonstrated that Ad-TRAIL-MRE-1-133-218 expressed in bladder cancer cells, rather than normal bladder cells. The differential TRAIL expression also led to selective apoptosis-inducing and growth-inhibiting effect of Ad-TRAIL-MRE-1-133-218 on bladder cancers. Finally, bladder cancer xenograft in mouse models further confirmed that Ad-TRAIL-MRE-1-133-218 effectively suppressed the growth of bladder cancers.ConclusionsCollectively, we demonstrated that MREs-based TRAIL delivery into bladder cancer cells was feasible and efficient for cancer gene therapy.

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