Triple-negative breast cancer (TNBC) lacks three important receptors, ER, PR, and HER2. It is more aggressive and more likely to relapse after treatment, thus has been identified as one of the most malignant breast cancer types. The development of efficient targeted TNBC therapy is an important research topic in TNBC treatment. We report the development of a new aptamer–drug conjugate (ApDC), AS1411–triptolide conjugate (ATC), as targeted therapy for the treatment of TNBC with high efficacy. The conjugate possesses excellent specificity and high cytotoxicity against the MDA-MB-231 cell line. The advantages of our newly invented ATC are further highlighted by its excellent in vivo anti-TNBC efficacy and negligible side effects toward healthy organs.
In the past decades, various nanomaterials with unique properties have been explored for bioapplications. Meanwhile, aptamers, generated from the systematic evolution of ligands by exponential enrichment technology, are becoming an indispensable element in the design of functional nanomaterials because of their small size, high stability, and convenient modification, especially endowing nanomaterials with recognition capability to specific targets. Therefore, the incorporation of aptamers into nanomaterials offers an unprecedented opportunity in the research fields of diagnostics and therapeutics. Here, we focus on recent advances in aptamer-embedded nanomaterials for bioapplications. First, we briefly introduce the properties of nanomaterials that can be functionalized with aptamers. Then, the applications of aptamer-embedded nanomaterials in cellular analysis, imaging, targeted drug delivery, gene editing, and cancer diagnosis/therapy are discussed. Finally, we provide some perspectives on the challenges and opportunities that have arisen from this promising area.
Biomarker‐guided anticancer strategy has evolved into one of the most reliable and efficient cancer treatment techniques. However, most targeted anticancer molecular platforms are constructed in liquid phase with multi‐step synthesis and complex purification. This work describes a general and modular solid‐phase synthesis strategy to engineer novel targeted anticancer therapeutics based on aptamer‐functionalized small molecule drugs (ASMD). Specifically, anticancer agent Combretastatin A4 (CA4) is transformed into a phosphoramidite module, and then is incorporated into aptamer Sgc8c via automated DNA synthesis technique to obtain intracellular phosphatase‐responsive Sgc8c‐CA4 conjugate (SC). In the rational design, SC retains excellent recognition ability and cytotoxicity against its target colorectal cancer cells. SC shows more efficient and safer therapy than CA4 both in vitro and in vivo. Moreover, the cellular events of SC are systematically visualized when they encounter the target cancer cells. The visualizing mechanism gives a clear picture of the anticancer function of targeted therapeutics against cancer cells. These results may pave the way for utilizing molecularly engineered ASMDs to develop more novel targeted cancer therapeutics for the treatment of different cancer types.
f Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is one of the most important viral diseases of birds globally, but little is currently known regarding enzootic trends of NDV in northeastern China, especially for class I viruses. Thus, we performed a surveillance study for NDV in northeastern China from 2013 to 2015. A total 755 samples from wild and domestic birds in wetlands and live bird markets (LBMs) were collected, and 10 isolates of NDV were identified. Genetic and phylogenetic analyses showed that five isolates from LBMs belong to class I subgenotype 1b, two (one from wild birds and one from LBMs) belong to the vaccine-like class II genotype II, and three (all from wild birds) belong to class II subgenotype Ib. Interestingly, the five class I isolates had epidemiological connections with viruses from southern, eastern, and southeastern China. Our findings, together with recent prevalence trends of class I and virulent class II NDV in China, suggest possible virus transmission between wild and domestic birds and the potential for an NDV epidemic in the future.
Avian paramyxovirus serotype 4 (APMV-4) is found sporadically in wild birds worldwide, and it is an economically important poultry pathogen. Despite the existence of several published strains, very little is known about the distribution, host species, and transmission of APMV-4 strains. To better understand the relationships among these factors, we conducted an APMV-4 surveillance of wild birds and domestic poultry in six provinces of China suspected of being intercontinental flyways and sites of interspecies transmission. APMV-4 surveillance was conducted in 9,160 wild birds representing seven species, and 1,461 domestic poultry in live bird markets (LMBs) from December 2013 to June 2016. The rate of APMV-4 isolation was 0.10% (11/10,621), and viruses were isolated from swan geese, bean geese, cormorants, mallards, and chickens. Sequencing and phylogenetic analyses of the 11 isolated viruses indicated that all the isolates belonging to genotype I were epidemiologically connected with wild bird-origin viruses from the Ukraine and Italy. Moreover, chicken-origin APMV-4 strains isolated from the LBMs were highly similar to wild bird-origin viruses from nearby lakes with free-living wild birds. In additional, a hemagglutination-negative APMV-4 virus was identified. These findings, together with recent APMV-4 studies, suggest potential virus interspecies transmission between wild birds and domestic poultry, and reveal possible epidemiological intercontinental connections between APMV-4 transmission by wild birds.
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