Background Attenuating inflammatory response and relieving pain are two therapeutic therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with practical targeting ability and other complementary strategies urgently need to be explored. To achieve this goal, an acupoint drug delivery system that can target deliver anti-inflammatory drugs and simulate acupuncture in relieving pain was constructed, which can co-deliver triptolide (TP) and 2-chloro-N (6)-cyclopentyl adenosine (CCPA). Results We have successfully demonstrated that acupoint nanocomposite hydrogel composed of TP-Human serum album nanoparticles (TP@HSA NPs) and CCPA could effectively treat RA. The result shows that CCPA-Gel can enhance analgesic effects specifically at the acupoint, while the mechanical and thermal pain threshold was 4.9 and 1.6 times compared with non-acupoint, respectively, and the nanocomposite gel further enhanced. Otherwise, the combination of acupoint and nanocomposite hydrogel exerted synergetic improvement of inflammation, bone erosion, and reduction of systemic toxicity. Furthermore, it could regulate inflammatory factors and restore the balance of Th17/Treg cells, which provided a novel and effective treatment strategy for RA. Interestingly, acupoint administration could improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48 h), which may explain the better therapeutic efficiency and low toxicity. Conclusion This novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine. Graphical Abstract

No abstract

Peripheral nerve injury gives rise to devastating conditions including neural dysfunction, unbearable pain and even paralysis. The therapeutic effect of current treatment for peripheral nerve injury is unsatisfactory, resulting in slow nerve regeneration and incomplete recovery of neural function. In this study, nerve suture combined with ADSCs injection was adopted in rat model of sciatic nerve injury. Under real-time visualization of the injected cells with the guidance of NIR-II fluorescence imaging in vivo, a spatio-temporal map displaying cell migration from the proximal injection site (0 day post-injection) of the nerve to the sutured site (7 days post-injection), and then to the distal section (14 days post-injection) was demonstrated. Furthermore, the results of electromyography and mechanical pain threshold indicated nerve regeneration and functional recovery after the combined therapy. Therefore, in the current study, the observed ADSCs migration in vivo, electrophysiological examination results and pathological changes all provided robust evidence for the efficacy of the applied treatment. Our approach of nerve suture combined with ADSCs injection in treating peripheral nerve injury under real-time NIR-II imaging monitoring in vivo added novel insights into the treatment for peripheral nerve injury, thus further enhancing in-depth understanding of peripheral nerve regeneration and the mechanism behind.

Treatment according to the dynamic changes of bacterial load in vivo is critical for preventing progression of bacterial infections. Here, we present a lead sulfide quantum dots (PbS QDs) based second near-infrared (NIR-II) fluorescence imaging strategy for bacteria detection and real-time in vivo monitoring. Four strains of bacteria were labeled with synthesized PbS QDs which showed high bacteria labeling efficiency in vitro. Then bacteria at different concentrations were injected subcutaneously on the back of male nude mice for in vivo imaging. A series of NIR-II images taken at a predetermined time manner demonstrated changing patterns of photoluminescence (PL) intensity of infected sites, dynamically imaging a changing bacterial load in real-time. A detection limit around 102–104 CFU/ml was also achieved in vivo. Furthermore, analysis of pathology of infected sites were performed, which showed high biocompatibility of PbS QDs. Therefore, under the guidance of our developed NIR-II imaging system, real-time detection and spatiotemporal monitoring of bacterial infection in vivo can be achieved, thus facilitating anti-infection treatment under the guidance of the dynamic imaging of bacterial load in future.