The efficacy of photosensitizers in cancer phototherapy is often limited by photobleaching, low tumor selectivity, and tumor hypoxia. Assembling photosensitizers into nanostructures can improve photodynamic therapy efficacy and the safety profile of photosensitizers. Herein by employing supramolecular assembly, enhanced theranostic capability of Mn2+-assisted assembly of a photosensitizer (sinoporphyrin sodium, DVDMS) is demonstrated. A tumor environment-triggered coassembly strategy is further developed to form Mn/DVDMS nanotheranostics (nanoDVD) for cancer phototherapy. MnO2 nanosheets serve as a highly effective DVDMS carrier and in situ oxygen and nanoDVD generator. In MCF-7 cells and xenograft tumors, MnO2/DVDMS is reduced by glutathione (GSH) and H2O2 and reassembled into nanoDVD, which can be monitored by activated magnetic resonance/fluorescence/photoacoustic signals. Intriguingly, the decrease of GSH, the production of O2, and the formation of nanoDVD are shown to be synergistic with phototherapy to improve antitumor efficacy in vitro and in vivo, offering a new avenue for cancer theranostics.
The greatest advantage of activatable fluorescence probes (AFPs) is the inherent responsiveness to manipulate spectroscopic properties by chemical/physical interactions with the biological analytes/microenvironmental factors. As alternatives to "always-on" fluorescence probes, AFPs in the first near-infrared (NIR-I) window expanded dramatically over the past decade and served as powerful tools in fluorescence biosensing and bioimaging. Benefiting from the deep tissue penetration, minimal tissue damage, and negligible background signal within longer wavelength, recent progress of fluorescent materials in the second near-infrared (NIR-II) window has been creating vast new opportunities in developing AFPs. Here, we review the current role of AFPs in biosensing and bioimaging, with emphasis on NIR-II AFPs developed for biomedical applications. The challenges and prospects of AFPs are also discussed by considering the clinical translation from bench to bedside.
It is a critically important challenge to rapidly design effective vaccines to reduce the morbidity and mortality of unexpected pandemics. Inspired from the way that most enveloped viruses hijack a host cell membrane and subsequently release by a budding process that requires cell membrane scission, we genetically engineered viral antigen to harbor into cell membrane, then form uniform spherical virus-mimetic nanovesicles (VMVs) that resemble natural virus in size, shape, and specific immunogenicity with the help of surfactants. Incubation of major cell membrane vesicles with surfactants generates a large amount of nano-sized uniform VMVs displaying the native conformational epitopes. With the diverse display of epitopes and viral envelope glycoproteins that can be functionally anchored onto VMVs, we demonstrate VMVs to be straightforward, robust and tunable nanobiotechnology platforms for fabricating antigen delivery systems against a wide range of enveloped viruses.virus-mimetic vesicle | vaccine | nanobiotechnology | antigen delivery system | cell membrane
Contrast agents (CAs) play a crucial role in high-quality magnetic resonance imaging (MRI) applications. At present, as a result of the Gd-based CAs which are associated with renal fibrosis as well as the inherent dark imaging characteristics of superparamagnetic iron oxide nanoparticles, Mn-based CAs which have a good biocompatibility and bright images are considered ideal for MRI. In addition, manganese oxide nanoparticles (MONs, such as MnO, MnO2, Mn3O4, and MnOx) have attracted attention as T1-weighted magnetic resonance CAs due to the short circulation time of Mn(II) ion chelate and the size-controlled circulation time of colloidal nanoparticles. In this review, recent advances in the use of MONs as MRI contrast agents for tumor detection and diagnosis are reported, as are the advances in in vivo toxicity, distribution and tumor microenvironment-responsive enhanced tumor chemotherapy and radiotherapy as well as photothermal and photodynamic therapies.
Self-assembled DNA nanostructures have attracted significant research interest in biomedical applications because of their excellent programmability and biocompatibility. To develop multifunctional drug delivery from DNA nanostructures, considerable key information is still needed for clinical application. Traditional fixed endpoint assays do not reflect the dynamic and heterogeneous responses of cells with regard to drugs, and may lead to the misinterpretation of experimental results. For the first time, an integrated time-lapse live cell imaging system was used to study the cellular internalization and controlled drug release profile of three different shaped DNA origami/doxorubicin (DOX) complexes for three days. Our results demonstrated the dependence of DNA nanostructures on shape for drug delivery efficiency, while the rigid 3D DNA origami triangle frame exhibited enhanced cellular uptake capability, as compared with flexible 2D DNA structures. In addition, the translocation of released DOX into the nucleus was proved by fluorescence microscopy, in which a DOX-loaded 3D DNA triangle frame displayed a stronger accumulation of DOX in nuclei. Moreover, given the facile drug loading and auto fluorescence of the anti-cancer drug, DOX, our results suggest that the DNA nanostructure is a promising candidate, as a label-free nanocarrier, for DOX delivery, with great potential for anticancer therapy as well.
To quantitatively assess the association between parity and all-cause mortality, we conducted a meta-analysis of cohort studies. Relevant reports were identified from PubMed and Embase databases. Cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) of all-cause mortality in three or more categories of parity were eligible. Eighteen articles with 2,813,418 participants were included. Results showed that participants with no live birth had higher risk of all-cause mortality (RR= 1.19, 95% CI = 1.03–1.38; I2 = 96.7%, P < 0.001) compared with participants with one or more live births. Nonlinear dose-response association was found between parity and all-cause mortality (P for non-linearity < 0.0001). Our findings suggest that moderate-level parity is inversely associated with all-cause mortality.
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