<p>Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy</p>

Abstract

BackgroundS-HM-3 is a tumor angiogenesis inhibitor with short half-life (25 min). In this present, TPGS/Solutol polymeric micelles was prepared to load together insoluble paclitaxel (PTX) and soluble S-HM-3, expecting to together deliver them to the tumor site with long-circulating, targeting function and combating multi-drug resistance (MDR).Materials and methodsPTX and S-HM-3 loaded TPGS/Solutol micelles (PHTSm) were prepared by the method of thin-film evaporation, and characterized by dynamic light scattering, transmission electron microscope (TEM), atomic force microscopy (AFM) and releasing properties. The anticancer effect of the polymeric micelles system was evaluated and confirmed by experiments of in vitro cell uptake study, in vivo pharmacokinetics, and pharmacodynamics studies.ResultsMicelles exhibited smooth spherical morphology with 20~30 nm and low critical micelle concentration (CMC) value of 0.000124 mg/mL. Only about 30% of PTX were slowly released from micelles at 48h, which can beneficial to the long circulation in blood. The results of in vitro cell assay proved that S-HM-3 could be easier to get into MDA-MB-231 cell, and its angiogenesis inhibition ability was also enhanced after integrating into micelles. In particular, the results of in vivo studies showed that the half-life of S-HM-3 and PTX was significantly prolonged 25.27 and 5.54 folds, and their AUC0–∞ was enhanced 129.78 and 15.65 times, respectively. Meanwhile 83.05% tumor inhibition rate of PHTSm was achieved compared with 59.99% of PTX.ConclusionsTPGS and Solutol micelles hold promising potential to resolve the conundrum of combined therapy of cytotoxic drug and angiogenesis inhibitor with different physicochemical property and anticancer mechanism in clinical use.

Nanomechanics in Monitoring the Effectiveness of Drugs Targeting the Cancer Cell Cytoskeleton

“…Taxanes and vinca alkaloids are not the only pair of microtubule-targeted agents studied. The other combinations employed are taxol/colchicine [ 70 ] or paclitaxel/S-HM -3 (a tumor angiogenesis inhibitor with a short half-life) [ 71 ]. Analogously to vincristine, colchicine destabilizes microtubules.…”

“…In another example, the structural and mechanical properties of the neuroblastoma SH-SY5Y cells induced by the N-methyl-D-aspartate (NMDA) receptors (a subtype glutamate receptor) were studied in a time-dependent manner. AFM reveals the rougher surface and more rigid cells attributed to the real-time degeneration [ 71 ]. Targeting the low-density lipoprotein receptor-related protein 1 (LRP-1) is considered a promising therapeutic target as LRP-1 can internalize the proteases involved in cancer progression.…”

Encapsulating Halofuginone Hydrobromide in TPGS Polymeric Micelles Enhances Efficacy Against Triple-Negative Breast Cancer Cells

“…Compared with other drug delivery systems, nanocarriers have multiple advantages, such as targeting, long-action time, low toxic effect, and wide drug-loading (DL) capacity. 20 , 21 Polymer micelles (PMs) can be self-assembled to form nanoparticles with a hydrophobic core and a hydrophilic shell. As a new type of drug vehicle, PMs have a high DL capacity, stable structure, long retention time in the body, and few adverse effects.…”

The Effects of Cetuximab and Cisplatin Anti-Cancer Drugs on the Mechanical Properties of the Lung Cancerous Cells Using Atomic Force Microscope

“…That is the reason that microtubules become goals for microtubule-targeted drugs (MTDs) applied in antitumor therapies [25]. On the other hand, some of the anti-cancer drugs are not interacting directly with the cellule cytoskeleton [26]. Some of the glycolytic enzymes are introduced associated with the cytoskeleton [26].…”

“…On the other hand, some of the anti-cancer drugs are not interacting directly with the cellule cytoskeleton [26]. Some of the glycolytic enzymes are introduced associated with the cytoskeleton [26]. These enzymes' detachment from the cytoskeleton displays in the reduction in glycolysis level and reconstructing of the cell cytoskeleton [27].…”