The efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particle that can be loaded with chemotherapeutics. We conjugate doxorubicin to poly(L-glutamic acid) via a pH-sensitive cleavable linker, and load the polymeric drug (pDox) into iNPG to assemble iNPG-pDox. Once released from iNPG, pDox spontaneously forms nanometer-sized particles in aqueous solution. Intravenously injected iNPG-pDox accumulates at tumors due to natural tropism and enhanced vascular dynamics and releases pDox nanoparticles that are internalized by tumor cells. Intracellularly, pDox nanoparticles are transported to the perinuclear region and cleaved into Dox, thereby avoiding excretion by drug efflux pumps. Compared to its individual components or current therapeutic formulations, iNPG-pDox shows enhanced efficacy in MDA-MB-231 and 4T1 mouse models of metastatic breast cancer, including functional cures in 40–50% of treated mice.
Piwi interacting RNAs (piRNAs) constitute novel small non-coding RNA molecules of approximately 24–31 nucleotides in length that often bind to members of the piwi protein family to play regulatory roles. Recently, emerging evidence suggests that in addition to the mammalian germline, piRNAs are also expressed in a tissue-specific manner in a variety of human tissues and modulate key signaling pathways at the transcriptional or post-transcriptional level. In addition, a growing number of studies have shown that piRNA and PIWI proteins, which are abnormally expressed in various cancers, may serve as novel biomarkers and therapeutic targets for tumor diagnostics and treatment. However, the functions of piRNAs in cancer and their underlying mechanisms remain incompletely understood. In this review, we discuss current findings regarding piRNA biogenetic processes, functions, and emerging roles in cancer, providing new insights regarding the potential applications of piRNAs and piwi proteins in cancer diagnosis and clinical treatment.
Semitransparent organic solar cells (ST-OSCs) can potentially meet the huge demands of off-grid and rooftop power supplies for advanced agricultural activities; yet, only a few efforts have been devoted to its development. Herein, we developed a high-performance spectrally engineered ST-OSCs using ''green'' fabrication for greenhouse. Empowered by the newly designed quaternary blends, OSCs were obtained with an excellent power conversion efficiency (PCE) of 17.71%. Such quaternary blends not only exhibit the suitable photon transmission windows for plant absorption but also retain excellent photovoltaic properties upon nonhalogenated solvent fabrication, leading to PCEs of 17.43% for opaque and 13.08% for ST-OSCs (with a plant growth factor of 24.7%), which represent the best-performed OSCs made from non-halogenated solvents. Under the ST-OSCs filtered lights, plants grow favorably, with growth being comparable with that under glass. This work provides an effective approach to constructing organic solar cells with promising features as eco-friendly greenhouse photovoltaics.
Organic photovoltaic cells (OPVs) have the potential of becoming a productive renewable energy technology if the requirements of low cost, high efficiency and prolonged lifetime are simultaneously fulfilled. So far, the remaining unfulfilled promise of this technology is its inadequate operational lifetime. Here, we demonstrate that the instability of NFA solar cells arises primarily from chemical changes at organic/inorganic interfaces bounding the bulk heterojunction active region. Encapsulated devices stabilized by additional protective buffer layers as well as the integration of a simple solution processed ultraviolet filtering layer, maintain 94% of their initial efficiency under simulated, 1 sun intensity, AM1.5 G irradiation for 1900 hours at 55 °C. Accelerated aging is also induced by exposure of light illumination intensities up to 27 suns, and operation temperatures as high as 65 °C. An extrapolated intrinsic lifetime of > 5.6 × 104 h is obtained, which is equivalent to 30 years outdoor exposure.
Polysaccharide is an abundant and reproducible natural material that is biocompatible and biodegradable. Polysaccharide and its derivatives also possess distinctive properties such as hydrophilicity, mechanical stability, as well as tunable functionality. Polysaccharide‐based hydrogels can be constructed via the physical and/or chemical crosslinking of polysaccharide derivatives with different functional molecules, as porous network structures or nanofibrillar structures. This review discusses the biomedical applications of polysaccharide‐based hydrogels containing native polysaccharides, polysaccharide derivatives, and polysaccharide‐composite hydrogels. Recent works on the fabrication, physical properties, advanced engineering, biomedical applications of cellulose‐, chitosan‐, alginate‐, and starch‐based hydrogels are also elaborated. Such porous swelling scaffolds exhibit great advantages at the interface of a negative pressure system such as wound dressing. In addition, the authors also discuss and summarize the exemplary research works of these hydrogels in the applications of drug release, wound dressing, and tissue engineering. Finally, challenges and future perspectives about the development of polysaccharide‐based hydrogels are discussed.
Site-specific localization is critical for improving the therapeutic efficacy and safety of drugs. Nanoparticles have emerged as promising tools for localized drug delivery. However, over 90% of systemically injected nanocarriers typically accumulate in the liver and spleen due to resident macrophages that form the mononuclear phagocyte system. In this study, the clinically approved antimalarial agent chloroquine was shown to reduce nanoparticle uptake in macrophages by suppressing endocytosis. Pretreatment of mice with a clinically relevant dose of chloroquine substantially decreased the accumulation of liposomes and silicon particles in the mononuclear phagocyte system and improved tumoritropic and organotropic delivery. The novel use of chloroquine as a macrophage-preconditioning agent presents a straightforward approach for addressing a major barrier in nanomedicine. Moreover, this priming strategy has broad applicability for improving the biodistribution and performance of particulate delivery systems. Ultimately, this study defines a paradigm for the combined use of macrophage-modulating agents with nanotherapeutics for improved site-specific delivery.
As a novel class of endogenous RNAs, circRNAs, have a covalently closed continuous loop, with neither a 5’to 3’polarity, nor a polyadenylated tail. Numerous circRNAs have been characterized by abundance, stabilization, conservation, and exhibit tissue/developmental stage-specific expression. Furthermore, circRNAs play vital roles in tumorigenesis and metastasis, such as functioning as a ceRNA or miRNA sponge, interacting with protein and encoding protein. Increasing evidence has revealed that it potentially serves as a required novel biomarker for cancer diagnosis. This review summarized the latest research on circRNAs, including its classification and biogenesis, mechanism and functions, as well as circRNAs in different cancers, as a potential biomarker.
A series of strict emission control measures were implemented in Beijing and surrounding regions to ensure good air quality during the 2014 Asia-Pacific Economic Cooperation (APEC) summit and 2015 Grand Military Parade (Parade), which led to blue sky days during these two events commonly referred to as “APEC Blue” and “Parade Blue”. Here we calculated Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) and Ozone Monitoring Instrument (OMI) NO2 and HCHO results based on well known DOAS trace gas fitting algorithm and WRF-Chem model (with measured climatology parameter and newest emission inventor) simulated trace gases profiles. We found the NO2 columns abruptly decreased both Parade (43%) and APEC (21%) compared with the periods before these two events. The back-trajectory cluster analysis and the potential source contribution function (PSCF) proved regional transport from southern peripheral cities plays a key role in pollutants observed at Beijing. The diminishing transport contribution from southern air mass during Parade manifests the real effect of emission control measures on NO2 pollution. Based on the ratios of HCHO over NO2 we found there were not only limited the NO2 pollutant but also suppress the O3 contaminant during Parade, while O3 increased during the APEC.
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