Enhanced Anti-Rheumatoid Arthritis Activity of Total Alkaloids from Picrasma Quassioides in Collagen-Induced Arthritis Rats by a Targeted Drug Delivery System.

New drug delivery systems have rarely been used in the formulation of traditional Chinese medicine, especially those that are crude active Chinese medicinal ingredients. In the present study, hyaluronic acid decorated lipid-polymer hybrid nanoparticles were used to prepare a targeted drug delivery system (TDDS) for total alkaloid extract from Picrasma quassioides (TAPQ) to improve its targeting property and anti-inflammatory activity. Picrasma quassioides, a common-used traditional Chinese medicine (TCM), containing a series of hydrophobic total alkaloids including ß-carboline and canthin-6-one alkaloids show great anti-inflammatory activity. However, its high toxicity (IC50= 8.088±0.903 µg/ml), poor water solubility (need to dissolve with 0.8% Tween-80) and poor targeting property severely limits its clinical application. Herein, hyaluronic acid (HA) decorated lipid-polymer hybrid nanoparticles loaded with TAPQ (TAPQ-NPs) were designed to overcome above mentioned deficiencies. TAPQ-NPs have good water solubility, strong anti-inflammatory activity and great joint targeting property. The in vitro anti-inflammatory activity assay showed that the efficacy of TAPQ-NPs was significantly higher than TAPQ(P<0.001). Animal experiments showed that the nanoparticles had good joint targeting property and had strong inhibitory activity against collagen-induced arthritis (CIA). These results indicate that the application of this novel targeted drug delivery system in the formulation of traditional Chinese medicine is feasible.

Self-Delivered and Self-Monitored Chemo-Photodynamic Nanoparticles with Light-Triggered Synergistic Antitumor Therapies by Downregulation of HIF-1α and Depletion of GSH.

Photodynamic therapy (PDT), a clinically approved cancer treatment, has faced many drawbacks that restricted its applications. For example, the hypoxia-induced elevated hypoxia-inducible factor-1α (HIF-1α) may desensitize tumors to PDT, and the high concentration of glutathione (GSH) in cancer cells can also neutralize the generated reactive oxygen species (ROS) during PDT, resulting in insufficient therapy. Moreover, extra probes for imaging-guided visualization therapy are always needed to track drug release or distribution, while it may decrease the drug loading of the drug delivery system (DDS). In the present study, we have designed and prepared a novel multifunctional combined therapy nanoparticle (ZnPc@Cur-S-OA NPs), in which curcumin (Cur) was not only used as a chemotherapy drug to achieve a combination therapy with PDT via downregulating HIF-1α and depleting GSH in B16F10 cells but also designed as a small-molecule ROS-triggered release prodrug to deliver the photosensitizer (PS). The red fluorescence of PS in the nanoparticles (NPs) can be used to track the NPs distribution, while the green fluorescence of Cur showed an "OFF-ON" activation, which enables additional imaging and real-time self-monitoring capabilities. These results proved that the prepared combined therapy NPs were more effective to inhibit the growth of B16F10 mouse melanoma tumor than was monotherapy without eliciting systemic toxicity either in vitro or in vivo, which indicated the combined therapy NPs as an effective way to improve the PDT efficacy via downregulation of HIF-1α and depletion of GSH. Thus, the strategy of using a multifunctional natural product as the stimuli-responsive carrier as well as the synergist with PDT for enhancing antitumor efficacy via multiple pathways may open an alternative avenue to fabricate new self-delivery combination therapy nanodrugs. Besides, the fluorescence emitted from the drug can be used for real-time self-monitoring of drug release and distribution, which has great potential in clinic to adjust the administration dose and irradiation time for different tumor types and stages for individual therapy.