Nanotechnology-empowered combination therapy for rheumatoid arthritis: principles, strategies, and challenges.

Rheumatoid arthritis (RA) is an autoimmune disease with multifactorial etiology and intricate pathogenesis. In RA, repeated monotherapy is frequently associated with inadequate efficacy, drug resistance, and severe side effects. Therefore, a shift has occurred in clinical practice toward combination therapy. However, conventional combination therapy encounters several hindrances, including low selectivity to arthritic joints, short half-lives, and varying pharmacokinetics among coupled drugs. Emerging nanotechnology offers an incomparable opportunity for developing advanced combination therapy against RA. First, it allows for co-delivering multiple drugs with augmented physicochemical properties, targeted delivery capabilities, and controlled release profiles. Second, it enables therapeutic nanomaterials development, thereby expanding combination regimens to include multifunctional nanomedicines. Lastly, it facilitates the construction of all-in-one nanoplatforms assembled with multiple modalities, such as phototherapy, sonodynamic therapy, and imaging. Thus, nanotechnology offers a promising solution to the current bottleneck in both RA treatment and diagnosis. This review summarizes the rationale, advantages, and recent advances in nano-empowered combination therapy for RA. It also discusses safety considerations, drug-drug interactions, and the potential for clinical translation. Additionally, it provides design tips and an outlook on future developments in nano-empowered combination therapy. The objective of this review is to achieve a comprehensive understanding of the mechanisms underlying combination therapy for RA and unlock the maximum potential of nanotechnology, thereby facilitating the smooth transition of research findings from the laboratory to clinical practice.

Nanomaterial-Based Drug Delivery Systems for Pain Treatment and Relief: From the Delivery of a Single Drug to Co-Delivery of Multiple Therapeutics.

The use of nanomaterials in drug delivery systems for pain treatment is becoming increasingly common. This review aims to summarize how nanomaterial-based drug delivery systems can be used to effectively treat and relieve pain, whether via the delivery of a single drug or a combination of multiple therapeutics. By utilizing nanoformulations, the solubility of analgesics can be increased. Meanwhile, controlled drug release and targeted delivery can be realized. These not only improve the pharmacokinetics and biodistribution of analgesics but also lead to improved pain relief effects with fewer side effects. Additionally, combination therapy is frequently applied to anesthesia and analgesia. The co-encapsulation of multiple therapeutics into a single nanoformulation for drug co-delivery has garnered significant interest. Numerous approaches using nanoformulation-based combination therapy have been developed and evaluated for pain management. These methods offer prolonged analgesic effects and reduced administration frequency by harnessing the synergy and co-action of multiple targets. However, it is important to note that these nanomaterial-based pain treatment methods are still in the exploratory stage and require further research to be effectively translated into clinical practice.

Adjoint traveltime tomography unravels a scenario of horizontal mantle flow beneath the North China craton.

The North China craton (NCC) was dominated by tectonic extension from late Cretaceous to Cenozoic, yet seismic studies on the relationship between crust extension and lithospheric mantle deformation are scarce. Here we present a three dimensional radially anisotropic model of NCC derived from adjoint traveltime tomography to address this issue. We find a prominent low S-wave velocity anomaly at lithospheric mantle depths beneath the Taihang Mountains, which extends eastward with a gradually decreasing amplitude. The horizontally elongated low-velocity anomaly is also featured by a distinctive positive radial anisotropy (VSH > VSV). Combining geodetic and other seismic measurements, we speculate the presence of a horizontal mantle flow beneath central and eastern NCC, which led to the extension of the overlying crust. We suggest that the rollback of Western Pacific slab likely played a pivotal role in generating the horizontal mantle flow at lithospheric depth beneath the central and eastern NCC.