Anti-migratory and increased cytotoxic effects of novel dual drug-loaded complex hybrid micelles in triple negative breast cancer cells

Abstract

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.

<p>^99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation</p>

“…Recent studies have shown that TPGS could play a role as an anticancer drug enhancer by inhibiting P-glycoprotein-mediated multidrug resistance in multiple tumor cells. [33][34][35][36][37][38] However, few investigations have involved the combination functions of therapy and diagnosis.…”

Mesoporous carbon nanoshells for high hydrophobic drug loading, multimodal optical imaging, controlled drug release, and synergistic therapy

“…The drug loading capacity of FMP-CNSs for PTX was 800.4 mg/g (~80.4 wt%), which is much higher than that previously-reported other mesoporous silica-based nanocarriers and hybrid micelles (<30.9 wt%). 26,63, 64 The appearance of the characteristic UV-Vis absorption peak of PTX at around 200 nm (Fig. 3d) confirms the successful loading of PTX molecules in FMP-CNSs.…”

Overcoming the Blood-Brain Barrier: Functionalised Chitosan Nanocarriers

“…Chitosan-based micelles or microemulsions were also found to be promising brain-targeting delivery systems due to their high brain biodistribution in in vivo studies For brain-targeted cancer treatment, Agrawal et al [96] developed chitosan micelles that were conjugated with transferrin and d-α-tocopherol PEG 1000 succinate (Figure 7B). This showed several benefits, including increased solubility of chitosan in acidic environments, the enhanced permeation of the NCs due to reversible opening of TJs, and inhibition of the P-gp [97][98][99][100]. The resulting micelles had an average size of 15 nm and an average ZP of −3 mV.…”