Rui Li's research while affiliated with Shanghai University of Traditional Chinese Medicine and other places

The therapeutic efficacy of chemotherapy in many types of hematological malignancies and solid tumors is dramatically hindered by multidrug resistance (MDR). This work presents a combination strategy of pretreatment of MDA-MB-231/MDR1 cells with quercetin (QU) followed by doxorubicin (DOX) to overcome MDR, which can be delivered by mixed micelles composed of the reduction-sensitive hyaluronic acid-based conjugate and D-α-tocopheryl polyethylene glycol 1000 succinate. The combination strategy can enhance the cytotoxicity of DOX on MDA-MB-231/MDR1 cells by increasing intracellular DOX accumulation and facilitating DOX-induced apoptosis. The probable MDR-reversal mechanisms are that the pretreatment cells with QU-loaded mixed micelles downregulate P-glycoprotein expression to decrease DOX efflux as well as initiate mitochondria-dependent apoptotic pathways to accelerate DOX-induced apoptosis. In addition, this combination strategy not only can potentiate in vivo tumor-targeting efficiency but also can enhance the anti-tumor effect in MDA-MB-231/MDR1-bearing nude mice without toxicity or side effects. This research suggests that the co-administration of natural compounds and chemotherapeutic drugs could be an effective strategy to overcome tumor MDR which deserves further exploration.

To address the dilemma of in vivo stability and anti-tumor effects of micellar drugs, novel organic and inorganic hybridized nanoparticle, that is, hyaluronic acid mineralized micelles, are designed to deliver paclitaxel (PTX) efficiently. The resulting micelles exhibit excellent drug loading capacities (30.6%) and entrapment efficiency (87.8%) for PTX with a small size (134.8 nm). Notably, the dual-sensitive release of PTX-loaded mineralized micelles is obtained in the condition of 40 mM GSH and pH 5.0, while release is slow in the physiological environment. With favorable cell uptake, mineralized micelles show decent tumor accumulation, which corresponds to their significant targeting capacity from the observed real-time images. Compared with Taxol, PTX-loaded mineralized micelles show a lower half-maximal inhibitory concentration (IC50) value (0.025 µg/mL), higher cell apoptosis rate (23.5%) in MDA-MB-231 cells, lower systemic toxicity to nude mice, and more potent in vivo tumor inhibition (1.57 times higher than Taxol (p < 0.05)).

Multidrug resistance (MDR) is a major obstacle to successful cancer therapy, especially for chemotherapy. Endogenous stimulus-responsive nanosystems (ESRNs), which were developed on the basis of the pathophysiological characteristics of the endogenous tumor microenvironment, have emerged as an efficient cancer therapy and have played an increasingly important role particularly in combating MDR cancers. These nanosystems can control the drug-releasing pattern temporally and spatially and can improve the accumulation of chemotherapeutic agents in MDR tumors or cells. This review focuses on recently published literature about nanosystems with endogenous stimulus-responsive features to overcome MDR, and it discusses their design and stimulus sensitivity, as well as their in vitro and in vivo anti-tumor efficacy in MDR tumors and cells.