Near-infrared light and redox dual-activatable nanosystems for synergistically cascaded cancer phototherapy with reduced skin photosensitization.

Currently, activatable photodynamic therapy (PDT) that is precisely regulated by endogenous or exogenous stimuli to selectively produce cytotoxic reactive oxygen species at the tumor site is urgently in demand. Herein, we fabricated a dual-activatable PDT nanosystem regulated by the redox tumor microenvironment and near-infrared (NIR) light-induced photothermal therapy (PTT). In this study, photosensitizer chlorin e6 (Ce6) was conjugated to hyaluronic acid (HA) via a diselenide bond to form an amphiphilic polymer (HSeC) for loading PTT agent IR780 to produce HSeC/IR nanoparticles (NPs). The photoactivity of Ce6 for PDT was "double-locked" by the aggregation-caused quenching (ACQ) effect and the fluorescence resonance energy transfer (FRET) from Ce6 to IR780 during blood circulation. After selective accumulation into tumors, HSeC/IR NPs were subsequently dissociated due to the "double-key", which included diselenide bond dissociation under high redox conditions and IR780 degradation upon NIR laser irradiation, resulting in recovering Ce6. In vitro studies indicated that Ce6 photoactivity in HSeC/IR NPs was significantly suppressed when compared with free Ce6 or in HSeC NPs. Moreover, BALB/c mice treated with HSeC/IR NPs displayed distinctly alleviated skin damage during PDT. Synergetic cascaded PTT-PDT with superior tumor suppression was observed in SCC7 tumor-bearing mice. Therefore, the study findings could provide a promising treatment strategy for PTT-facilitated PDT with high antitumor efficacies and reduced skin phototoxicity levels.

Electro-acupuncture for post-stroke cognitive impairment: A protocol for systematic review and meta-analysis.

BACKGROUND: A considerable number of stroke survivors suffered from cognitive impairment, and more than one third of stroke survivors are affected at 3 and 12 months after the stroke. Although the published systematic reviews suggest that acupuncture can help improve post-stroke cognitive dysfunction, the power of the results is low due to study limitations. Therefore, this review is necessary to analyze the effect of acupuncture on cognitive impairment after stroke and to provide evidence for cognitive impairment in stroke. METHODS: This study will be carried out in strict accordance with the Cochrane Handbook for Systematic Reviews of Interventions. According to the pre-established search strategy (PICOS framework), all the literature will be obtained from online databases including Cochrane Central Register of Controlled Trials in the Cochrane Library, Medline (via PubMed), EMBASE (via embase.com), CINAHL (via EBSCOhost), China National Knowledge Infrastructure database, WanFang Database, Chinese Science and Technology Periodical Database, and Sino-Med Database from inception until December 31, 2021 with no language limitations. Two reviewers will screen the records and include quality studies according to inclusion criteria independently. The data needed will be extracted independently by 2 authors according to a table of data extraction. Any inconsistencies in literature screening and data collection will be resolved to reach a consensus via discussion with a third author. Risk of bias for each study will be assessed using risk of bias tool. RevMan5.3 will be used to analyze the data. Heterogeneity will be identified and measured by Chi2. Subgroup analyses and sensitivity analysis will be carried out. Grading of Recommendations Assessment, Development and Evaluation will be used to evaluate the evidence for each outcome. CONCLUSION: The results of this study will provide a theoretical basis for the clinical use of electro-acupuncture to treat cognitive dysfunction after stroke. UNIQUE INPLASY NUMBER: INPLASY202210038.

Assessment of the reporting quality of randomised controlled trials of massage.

OBJECTIVE: To assess the reporting quality of randomised controlled trials (RCTs) of massage, particularly whether necessary elements related to massage interventions were adequately reported. METHODS: A total of 8 electronic databases were systematically searched for massage RCTs published in English and Chinese from the date of their inception to June 22, 2020. Quality assessment was performed using three instruments, namely the CONSORT (Consolidated Standards of Reporting Trials) 2010 Checklist (37 items), the CONSORT Extension for NPT (Nonpharmacologic Treatments) 2017 checklist (18 items), and a self-designed massage-specific checklist (16 items) which included massage rationale, intervention and control group details. Descriptive statistics were additionally used to analyse the baseline characteristics of included trials. RESULTS: A total of 2,447 massage RCTs were identified, of which most (96.8%) were distributed in China. For the completeness of CONSORT, NPT Extension, and massage-specific checklists, the average reporting percentages were 50%, 10% and 45%, respectively. Of 68 assessed items in total (exclusion of 3 repeated items on intervention), 42 were poorly presented, including 18 CONSORT items, 15 NPT items, and 9 massage-specific items. Although the overall quality of reporting showed slightly improvement in articles published after 2010, the international (English) journals presented a higher score of the CONSORT and NPT items, while the Chinese journals were associated with the increased score of massage-specific items. CONCLUSION: The quality of reporting of published massage RCTs is variable and in need of improvement. Reporting guideline "CONSORT extension for massage" should be developed.

Self-Propelled and Near-Infrared-Phototaxic Photosynthetic Bacteria as Photothermal Agents for Hypoxia-Targeted Cancer Therapy.

Hypoxia can increase the resistance of tumor cells to radiotherapy and chemotherapy. However, the dense extracellular matrix, high interstitial fluid pressure, and irregular blood supply often serve as physical barriers to inhibit penetration of drugs or nanodrugs across tumor blood microvessels into hypoxic regions. Therefore, it is of great significance and highly desirable to improve the efficiency of hypoxia-targeted therapy. In this work, living photosynthetic bacteria (PSB) are utilized as hypoxia-targeted carriers for hypoxic tumor therapy due to their near-infrared (NIR) chemotaxis and their physiological characteristics as facultative aerobes. More interestingly, we discovered that PSB can serve as a kind of photothermal agent to generate heat through nonradiative relaxation pathways due to their strong photoabsorption in the NIR region. Therefore, PSB integrate the properties of hypoxia targeting and photothermal therapeutic agents in an "all-in-one" manner, and no postmodification is needed to achieve hypoxia-targeted cancer therapy. Moreover, as natural bacteria, noncytotoxic PSB were found to enhance immune response that induced the infiltration of cytotoxicity T lymphocyte. Our results indicate PSB specifically accumulate in hypoxic tumor regions, and they show a high efficiency in the elimination of cancer cells. This proof of concept may provide a smart therapeutic system in the field of hypoxia-targeted photothermal therapeutic platforms.

Injectable and thermally contractible hydroxypropyl methyl cellulose/Fe3O4 for magnetic hyperthermia ablation of tumors.

The development of efficient strategies for the magnetic hyperthermia ablation of tumors remains challenging. To overcome the significant safety limitations, we developed a thermally contractible, injectable and biodegradable material for the minimally invasive and highly efficient magnetic hyperthermia ablation of tumors. This material was composed of hydroxypropyl methyl cellulose (HPMC), polyvinyl alcohol (PVA) and Fe3O4. The thermal contractibility of HPMC/Fe3O4 was designed to avoid damaging the surrounding normal tissue upon heating, which was confirmed by visual inspection, ultrasound imaging and computed tomography (CT). The efficient injectability of HPMC/Fe3O4 was proven using a very small needle. The biosafety of HPMC/Fe3O4 was evaluated by MTT and biochemical assays as well as flow cytometry (FCM). All the aforementioned data demonstrated the safety of HPMC/Fe3O4. The results of in vitro and ex vivo experiments showed that the temperature and necrotic volume of excised bovine liver were positively correlated with the HPMC/Fe3O4 weight, iron content and heating duration. The in vivo experimental results showed that the tumors could be completely ablated using 0.06 ml of HPMC/60%Fe3O4 after 180 s of induction heating. We believe that this novel, safe and biodegradable material will promote the rapid bench-to-bed translation of magnetic hyperthermia technology, and it is also expected to bring a new concept for the biomaterial research field.