Si-Shen Feng

A polymer-based nanocarrier was developed for the co-delivery of epigenetic and chemotherapeutic drugs. The sterically stabilized hybrid micelle system uses micelles composed of D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000). In this study, suberoylanilide hydroxamic acid (SAHA) and paclitaxel were used as model drugs for combination chemotherapy to enhance therapeutic efficiency in targeting mesenchyme-like triple negative breast cancer (TNBC) cells. Combination therapy of paclitaxel and SAHA in a dual drug micelle system, (P + S)_mic, exhibited an IC50 value of 0.52 μg/mL, which is about 5.91-fold more cytotoxic than the mere combination of free drugs (P + S). Furthermore, the (P + S)_mic formulation was far more effective at inhibiting cell migration by more than 3.4-fold than the control. Thus, our findings show that the co-delivery of these drugs using the micelle system greatly enhances their therapeutic effect at a lower dosage, thereby minimizing toxicity. In addition, this formulation is proved to be remarkably effective in preventing cell migration at low dosage.

A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors have great advantages to solve the problem, if the bottleneck of their delivery could be well addressed by the various nanocarriers. Moreover, co-delivery of siRNA together with the various anticancer agents in one nanocarrier may maximize their additive or synergistic effect. This review provides a comprehensive summary on the state-of-the-art of the nanocarriers, which may include prodrugs, micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles, nanoparticles of biodegradable polymers and nucleic acid nanocarriers for delivery of siRNA and co-delivery of siRNA together with anticancer agents with focus on synthesis of the nanocarrier materials, design and characterization, in vitro and in vivo evaluation, and prospect and challenges of nanocarriers.

A dendritic amphiphilic block copolymer H40‐poly(d,l‐lactide)‐block‐d‐α‐tocopheryl polyethylene glycol 1000 succinate (H40‐PLA‐b‐TPGS) is synthesized, which is then employed to develop a system of nanoparticles (NPs) loaded with docetaxel (DTX) as a model drug for cancer treatment due to its higher drug‐loading content and drug encapsulation efficiency, smaller particle size, faster drug release, and higher cellular uptake in comparison to the linear PLA polymer NPs and PLA‐b‐TPGS copolymer NPs. The drug‐loaded NPs are prepared by a modified nanoprecipitation method and characterized in terms of size and size distribution, surface morphology, drug release profile, and physical state of DTX. Cellular uptake of coumarin 6‐loaded NPs by MCF‐7 cancer cells is determined by flow cytometry and confocal laser scanning microscopy. The antitumor efficacy of the drug‐loaded NPs is investigated in vitro by MTT assay and in vivo by xenograft tumor model. The 72 h IC50 of the drug formulated in the PLA, PLA‐b‐TPGS, and H40‐PLA‐b‐TPGS NPs is found to be, 1.5 ± 0.3, 0.9 ± 0.1, and 0.15 ± 0.06 μg mL⁻¹, which are 7.3, 12.2, and 73.3‐fold effective than 11.0 ± 1.2 μg mL⁻¹ for Taxotere, respectively. Such advantages are further confirmed by the measurement of the tumor size and weight.