Single-molecule detection provides a simple and ultrasensitive platform to quantify target molecules by simply counting the individual fluorescence signals. Quantum dots (QDs) are novel semiconductor nanocrystals with distinct characteristics of high brightness, large Stokes shift and broad absorption spectra, high molar extinction coefficients, high quantum yield, good photostability and long fluorescence lifetime. The combination of single-molecule detection with QDs enables the development of single QD-based nanosensors with extremely high sensitivity. Single QD-based nanosensors may be divided into two categories based on single QD burst coincidence detection and single QD-fluorescence resonance energy transfer (FRET) detection, and have significant advantages of high signal-to-noise ratio, high sensitivity, rapidity, and low sample consumption. The single QD-based nanosensors have the capability of directly detecting low-abundance species without the need for nucleic acid amplification, and may elucidate a variety of biological and biochemical phenomena in real time using single QD tracking. In this review, we summarize the recent advances in single QD-based nanosensors and their applications for sensitive detection of DNAs, microRNAs, proteins, enzymes, small molecules and viruses. We highlight the challenges and future direction of single QD-based nanosensors as well.
Carrier-free prodrug-nanoassemblies have emerged as promising nanomedicines. In particular, the self-assembled nanoparticles (NPs) composed of homodimeric prodrugs with ultrahigh drug loading have attracted broad attention. However, most homodimeric prodrugs show poor self-assembly ability due to their symmetric structures. Herein, we developed photosensitizer-driven nanoassemblies of homodimeric prodrug for self-enhancing activation and chemo-photodynamic synergistic therapy.
Methods:
In this work, a pyropheophorbide a (PPa)-driven nanoassemblies of an oxidation-responsive cabazitaxel homodimer (CTX-S-CTX) was fabricated (pCTX-S-CTX/PPa NPs). The assembly mechanisms, aggregation-caused quenching (ACQ) effect alleviation, singlet oxygen generation, self-enhancing prodrug activation, cellular uptake, intracellular reactive oxygen species (ROS) generation and synergistic cytotoxicity of pCTX-S-CTX/PPa NPs were investigated
in vitro
. Moreover, the pharmacokinetics,
ex vivo
biodistribution and
in vivo
therapeutic efficacy of pCTX-S-CTX/PPa NPs were studied in mice bearing 4T1 tumor.
Results:
Interestingly, PPa was found to drive the assembly of CTX-S-CTX, which cannot self-assemble into stable NPs alone. Multiple intermolecular forces were found to be involved in the assembly process. Notably, the nanostructure was destroyed in the presence of endogenous ROS, significantly relieving the ACQ effect of PPa. In turn, ROS generated by PPa under laser irradiation together with the endogenous ROS synergistically promoted prodrug activation. As expected, the nanoassemblies demonstrated potent antitumor activity in a 4T1 breast cancer BALB/c mice xenograft model.
Conclusion:
Our findings offer a simple strategy to facilitate the assembly of homodimeric prodrugs and provide an efficient nanoplatform for chemo-photodynamic therapy.
A B S T R A C TThe role of graphene oxide (GO) on anaerobic digestion (AD) of swine manure concerning the performance, microbial community and antibiotic resistance genes (ARGs) reduction was investigated. Results showed that methane production was reduced by 13.1%, 10.6%, 2.7% and 17.1% at GO concentration of 5 mg/L, 50 mg/L, 100 mg/L and 500 mg/L, respectively, but propionate degradation was enhanced along with GO addition. Both bacterial and archaeal community changed little after GO addition. AD could well reduce ARGs abundance, but it was deteriorated at the GO concentration of 50 mg/L and 100 mg/L and enhanced at 500 mg/L, while no obvious changes at 5 mg/L. Network and SEM analysis indicated that changes of each ARG was closely associated with variation of microbial community composition, environmental variables contributed most to the dynamics of ARGs indirectly, GO influenced the ARGs dynamics negatively and (heavy metal resistance genes (MRGs)) influenced the most directly.
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