Here, we report the one-step in situ detection of targeted miRNAs expression in single living cancer cells via MoS nanosheet-based fluorescence on/off probes. The strategy is based on the folic acid (FA)-poly(ethylene glycol)-functionalized MoS nanosheets with adsorbed dye-labeled single-stranded DNA (ssDNA). Once the nanoprobes are internalized into cancer cells, the hybridization between the probes and target miRNA results in the detachment of dye-labeled ssDNA from MoS nanosheets surface, leading to the green fluorescence recovery. In this nanoprobe, MoS nanosheets offer advantages of high fluorescence quenching efficiency and extremely low toxicity. The FA conjugation could protect the probes and improve cancer cell transfection efficiency. The ability of this nanoprobe for endogenous miRNA detection in single living cancer cells is demonstrated for two types of cancer cells with different miRNA-21 expressions (MCF-7 and Hela cells). This functionalized MoS nanosheet-based nanoprobes could provide a sensitive and real-time detection of intracellular miRNA detection platform.

COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.

Osteoarthritis (OA) is a leading cause of chronic pain in the elderly worldwide. Yet current diagnosis and therapy for OA pain are subjective and nonspecific with significant adverse effects. Here, we introduced a theranostic nanoprobe based on molybdenum disulfide nanosheet-coated gold nanorods (MoS2-AuNR) targeting never growth factor (NGF), a key player in pain sensation, for photoacoustic pain imaging and near-infrared (NIR) imaging-guided photothermal analgesic therapy. MoS2 coating significantly improved the photoacoustic and photothermal performance of AuNR. Functionalization of MoS2-AuNR nanoprobes by conjugating with NGF antibody enabled active targeting on painful OA knees in a surgical OA murine model. We observed that our functional nanoprobes accumulated in the OA knee rather than the contralateral intact one, and the amount was correlated with the severity of mechanical allodynia in our mouse model. Under imaging guidance, NIR-excited photothermal therapy could mitigate mechanical allodynia and walking imbalance behavior for both subacute and chronic stages of OA in a preclinical setting. This molecular theranostic approach enabled us to specifically localize the source of OA pain and efficiently block peripheral pain transmission.

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