A strategy to expand anti-Stokes shifting from the far-red to deep-blue region in metal-free triplet–triplet annihilation upconversion (TTA-UC) is presented and its utility in the in vivo titration of the photorelease of an anticancer prodrug is demonstrated. This new TTA system has robust brightness and the longest anti-Stokes shift of any reported TTA system. TTA core-shell-structured prodrug delivery capsules that benefit from these properties are developed; they can operate with low-power-density far-red light-emitting diode (LED) light. These capsules contain mesoporous silica nanoparticles preloaded with TTA molecules as the core and amphiphilic polymers encapsulating anticancer prodrug molecules as the shell. When stimulated by far-red light, the intense TTA upconversion blue emssison in the system activates the anticancer prodrug molecules and shows effective tumor growth inhibition in vivo. This work paves the way for the design of new organic TTA upconversion with regard to in vivo photocontrollable drug release and other biophotonic applications.
A monoclonal antibody (mAb) against 4-(diethoxyphosphorothioyloxy)benzoic acid (hapten 1) was raised and used to develop a broad-specificity competitive indirect enzyme-linked immunosorbent assay (ciELISA) for 14 O,O-diethyl organophosphorus pesticides (OPs). Computer-assisted molecular modeling was used to model two-dimensional (2D) and three-dimensional (3D) quantitative structure-activity relationships (QSARs) to study antibody recognition. On the basis of insights obtained from the QSAR models, two heterologous coating haptens, 4-(diethoxyphosphorothioylamino)butanoic acid (hapten 2) and 4-(diethoxyphosphorothioyloxy)-2-methylbenzoic acid (hapten 3) were designed, synthesized, and used to develop heterologous ciELISAs with significantly improved sensitivity. The heterologous ciELISA using hapten 2 as the coating hapten showed good sensitivity in a broad-specific manner for eight O,O-diethyl OPs and may be used as a screening method for the determination of these OPs. Our studies demonstrated that molecular modeling can provide insights into the spatial and electronic effects of molecular structures that are important for antibody activity, which can then be used to improve immunoassay sensitivity.
Graphical abstract
Resonance energy transfer constructed NIR-absorbing BODIPY-based photosensitized dyad (RET-BDP) nanoparticles are developed. These nanoparticles enable targeted photodynamic therapy upon application of low-power NIR LED light irradiation. This work provides a new concept for the design of biocompatible nanoparticles with significantly improved NIR sensitivity, which is key to PDT development.
The mortality rate of hemorrhagic African swine fever (ASF), which targets domestic pigs and wild boars is caused by African swine fever virus (ASFV), can reach 100%. Since the first confirmed ASF outbreak in China on 3 August 2018, 156 ASF outbreaks were detected in 32 provinces. About 1,170,000 pigs were culled in order to halt further spread. There is no effective treatment or vaccine for it and the present molecular diagnosis technologies have trade-offs in sensitivity, specificity, cost and speed, and none of them cater perfectly to ASF control. Thus, a technology that overcomes the need for laboratory facilities, is relatively low cost, and rapidly and sensitively detects ASFV would be highly valuable. Here, we describe an RAA-Cas12a-based system that combines recombinase aided amplification (RAA) and CRISPR/Cas12a for ASFV detection. The fluorescence intensity readout of this system detected ASFV p72 gene levels as low as 10 aM. For on-site ASFV detection, lateral-flow strip readout was introduced for the first time in the RAA-Cas12a based system (named CORDS, Cas12abased On-site and Rapid Detection System). We used CORDS to detect target DNA highly specifically using the lateral-flow strip readout and the assay displayed no crossreactivity to other 13 swine viruses including classical swine fever (CSF). CORDS could identify the ASFV DNA target at femtomolar sensitivity in an hour at 37 • C, and only requires an incubator. For ease of use, the reagents of CORDS were lyophilized to three tubes and remained the same sensitivity when stored at 4 • C for at least 7 days. Thus, CORDS provide a rapid, sensitive and easily operable method for ASFV on-site detection. Lyophilized CORDS can withstand long-term transportation and storage, and is ready for field-based applications.
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