DNA-Functionalized Porphyrinic Metal-Organic Framework-Based Drug Delivery System for Targeted Bimodal Cancer Therapy.

A DNA-functionalized porphyrinic MOF (porMOF) drug delivery system was successfully constructed. porMOF as a photosensitizer and drug delivery carrier can integrate photodynamic therapy (PDT) and chemotherapy. Via the strong coordination interaction between the zirconium cluster of porMOF and the terminal phosphate group of DNA, the stable modification of the DNA layer on the porMOF surface is achieved. Meanwhile, the introduction of C/G-rich base pairs into the DNA double-stranded structure provides more binding sites of chemotherapeutic drug doxorubicin (DOX). AS1411, an aptamer of nucleolin proteins that are overexpressed by cancer cells, is introduced in the double-stranded terminal, which can endow the nanosystem with the ability to selectively recognize cancer cells. C-rich sequences in DNA double strands form an i-motif structure under acidic conditions to promote the highly efficient release of DOX in cancer cells. In vitro and in vivo experiments demonstrate that the synergistic PDT/chemotherapy modality achieves highly efficient cancer cell killing and tumor ablation without undesirable side effects.

Exercise interventions on patients with end-stage renal disease: a systematic review.

OBJECTIVE:: This study aimed to conduct an up-to-date systematic review of the literature to evaluate the effects of exercise on fatigue, anxiety, depression, physical activity, and quality of life (QOL) in patients with end-stage renal disease. DATA SOURCES:: We searched PubMed (October 2018), Embase (from 1966 to October 2018), Web of Science (from 1900 to October 2018), The Cochrane Library (October 2018), and references of papers. METHODS:: This study includes randomized controlled trials that analyzed the combined effects of exercise intervention on patients with end-stage renal disease. Two reviewers independently screened the retrieved records, extracted data, and assessed the risk of bias for inclusion in the study. The effects of exercise intervention were conducted in the meta-analysis using RevMan 5.3 software. RESULTS:: A total of 614 participants were included in 13 randomized controlled studies. The study revealed that exercise can improve fatigue, anxiety, depression, physical activity, and QOL. The effect value results were as follows: (1) fatigue, -0.97 (95% confidence interval (CI) -1.32 to -0.62, P < 0.00001); (2) anxiety, -0.78 (95% CI -1.17 to -0.39, P < 0.0001); (3) depression, -0.85 (95% CI -1.13 to -0.56, P < 0.00001) (4) physical activity, 38.15 (95% CI 21.20 to 55.10, P < 0.0001); (5) QOL, the physical component of the 36-item Short-Form Health Survey (SF-36), 4.73 (95% CI 1.92 to 7.54, P = 0.0010); and (6) the mental component of the SF-36, 3.42 (95% CI 0.27 to 6.56, P = 0.03). CONCLUSION:: Exercise intervention is more effective in fatigue, anxiety, depression, physical activity, and QOL. However, large-scale randomized controlled trials are needed to confirm the appropriate types of exercise and optimal time for patients with end-stage renal disease.

A ZnO-gated porphyrinic metal-organic framework-based drug delivery system for targeted bimodal cancer therapy.

To overcome the side effects caused by premature drug leakage from carriers and to achieve more efficient cancer treatment via the synergy of photodynamic therapy (PDT) and chemotherapy, a porphyrinic metal-organic framework (porMOF)-based drug delivery system (ZnO-gated porMOF-AS1411) was prepared and its ability to efficiently deliver small molecule drugs was tested. In this system, the porous porMOF plays the dual roles of a PDT photosensitizer and a drug carrier. To overcome premature drug leakage and thus reduce side effects and improve drug delivery efficiency, pH-sensitive ZnO nanoparticles were used to cover the porMOF nanopores. Neutral and alkaline pH-stable ZnO ensured that the loaded drugs were encapsulated in the porMOF pores during delivery. However, ZnO disintegration in the acidic lysosomal environment opened the pores, permitting drug release. Further assembly of nucleolin-specific AS1411 aptamers conferred the nanosystem with target-specific recognition and accumulation abilities. In this work, we demonstrated that the proposed nanosystem could be successfully used to efficiently deliver, with controllable release, the chemotherapeutic drug doxorubicin (DOX), thus achieving bimodal cancer treatment by PDT and chemotherapy. In vitro and in vivo experiments demonstrated that this synergistic therapeutic modality achieved highly efficient cancer cell-killing and tumor ablation without undesirable side effects.