Great challenges in investigating the release of drug in complex cellular microenvironments necessitate the development of stimuli-responsive drug delivery systems with real-time monitoring capability. In this work, a smart drug nanocarrier based on fluorescence resonance energy transfer (FRET) is fabricated by capping graphene quantum dots (GQDs, the acceptor) onto fluorescent mesoporous silica nanoparticles (FMSNs, the donor) via ATP aptamer for real-time monitoring of ATP-triggered drug release. Under extracellular conditions, the fluorescence of FMSNs remains in the "off" state in the low ATP level which is unable to trigger the release of drug. Once specifically recognized and internalized into the target tumor cells by AS1411 aptamer, in the ATP-rich cytoplasm, the conformation switch of the ATP aptamer causes the shedding of the GQDs from the nanocarriers, leading to the release of the loaded drugs and consequently severe cytotoxicity. Simultaneously, the fluorescence of FMSNs turns "on" along with the dissociation of GQDs, which allows real-time monitoring of the release of drug from the pores. Such a drug delivery system features high specificity of dual-target recognition with AS1411 and ATP aptamer as well as high sensitivity of the FRET-based monitoring strategy. Thus, the proposed multifunctional ATP triggered FRET-nanocarriers will find potential applications for versatile drug-release monitoring, efficient drug transport, and targeted cancer therapeutics.

Highlights d Radio-frequency (RF) waves activate ferritin-tagged channels via a biochemical pathway d RF interacts with ferritins, increasing the levels of free iron (labile iron pool) d Free iron produces reactive oxygen species and oxidizes membrane lipids d RF activates ferritin-tagged channels via iron-induced lipid oxidation

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A highly sensitive and selective photoelectrochemical (PEC) biosensor for Hg(2+) detection was developed on the basis of the synergistic effect of exciton energy transfer (EET) between CdS quantum dots (QDs) and Au nanoparticles (NPs) coupled with sensitization of rhodamine 123 (Rh123) for signal amplification. First, the TiO2/CdS hybrid structure obtained by depositing CdS QDs on TiO2 film was employed as a matrix for immobilizing probe DNA (pDNA). Next, Rh123 was introduced into the pDNA terminal, and then Au NP labeled target DNA (Au-tDNA) was hybridized with pDNA to form a rod-like double helix structure. The detection of Hg(2+) was based on a conformational change of the pDNA after incubating with Hg(2+). In the absence of Hg(2+), Rh123 was located away from the electrode surface due to the DNA hybridization, leading to inhibition of the sensitization effect, and meanwhile, the occurrence of EET between CdS QDs and Au NPs resulted in a photocurrent decrease. However, after incubating with Hg(2+), the rod-like double helix was disrupted, and the energy transfer was broken. In this case, the photocurrent recovered, and meanwhile, the folded pDNA made the labeled Rh123 move closer to the electrode surface, leading to the formation of the sensitization structure, which evidently increased the photocurrent intensity. The sensitivity of the biosensor for Hg(2+) detection was greatly enhanced for the dual signal amplification strategy. The linear range was 10 fM to 200 nM, with a detection limit of 3.3 fM. This biosensor provides a promising new platform for detecting various heavy metal ions at ultralow levels.

The replacement of aryl rings with saturated carbocyclic structures has garnered significant interest in drug discovery due to the potential for improved pharmacokinetic properties upon substitution. In particular, 1,3-difunctionalized bicyclo[1.1.1]pentanes (BCPs) have been widely adopted as bioisosteres for parasubstituted arene rings, appearing in a number of lead pharmaceutical candidates. However, despite the pharmaceutical value of 2-substituted BCPs as replacements for ortho- or meta-substituted arene rings, general and rapid syntheses of these scaffolds remain elusive. Current approaches to 2-substituted BCPs rely on installation of the bridge substituent prior to BCP core construction, leading to lengthy step counts and often nonmodular sequences. While challenging, direct functionalization of the strong bridge BCP C–H bonds would offer a more streamlined pathway to diverse 2-substituted BCPs. Here, we report a generalizable synthetic linchpin strategy for bridge functionalization via radical C–H abstraction of the BCP core. Through mild generation of a strong hydrogen atom abstractor, we rapidly synthesize novel 2-substituted BCP synthetic linchpins in one pot. These synthetic linchpins then serve as common precursors to complex 2-substituted BCPs, allowing one-step access to a number of previously inaccessible electrophile and nucleophile fragments at the 2-position via two new metallaphotoredox protocols. Altogether, this platform enables the expedient synthesis of four pharmaceutical analogues, all of which show similar or improved properties compared to their aryl-containing equivalents, demonstrating the potential of these 2-substituted BCPs in drug development.