Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer.

A novel pH/redox-responsive hyperbranched MeO-PEG-b-(NIPAAm-co-PBAE) nanoparticles (NPs) were designed with size shrinkage and charge-reversible potential for targeted delivery of docetaxel (DTX) to MDA-MB-231 cell lines. In the tumor microenvironment (TME), amine protonation induces charge reversal and disulfide bond cleavage under high TME GSH concentration causing size shrinkage, improved deep tumor penetration, and active targeting of the therapeutic agents. These nano drug delivery systems (NDDSs) significantly promoted cancer cell uptake (~ 100% at 0.5 h), facilitating site-specific delivery and deep tumor penetration. The MTT assay revealed significantly higher cytotoxicity (P value < 0.0001) for DTX-loaded NPs compared to free DTX. Cell cycle analysis revealed G2/M (58.3 ± 2.1%) and S (21.5 ± 1.3%) arrest for DTX-loaded NPs, while free DTX caused G2/M (67.9 ± 1.1%) and sub-G1 (10.3 ± 0.8%) arrest. DTX-loaded NPs induced higher apoptosis (P value < 0.001) in MDA-MB-231 cells (71.5 ± 2.8%) compared to free DTX (42.3 ± 3.1%). Western blotting and RT-PCR assays confirmed significant up-regulation of protein levels and apoptotic genes by DTX-loaded NPs compared to free DTX. In conclusion, TME-responsive charge reversal and size-shrinkable smart NDDSs designed based on low pH, and high glutathione (GSH), offer more effective site-specific delivery of therapeutic agents to tumors.

Dye stability of black cherry plum anthocyanins in the interaction with co-pigments and sucrose sweetener.

In this research, the co-pigmentation reactions between black cherry plum (Prunus cerasifera Ehrh. cv. Pissardii Nigra) anthocyanins and caffeic, gallic, 4-hydroxybenzoic, malic, and tannic acids with different concentrations (0, 120, 240, 480, and 960 mg L-1) at various temperatures (20, 40, 60, 80, and 100°C) were investigated at pH 3.5. The strongest immediate co-pigmentations resulted at 960 mg L-1, being significantly highest using tannic acid at all temperatures. In addition, the anthocyanin stability and the brown polymeric color formation were investigated in the presence of different concentrations of sucrose sweetener (0, 30, and 60%) and different pHs (2 and 3) in the range of 0-60 h. Also, the amount of furfural was measured in the presence of 0% and 30% sucrose concentrations at pH 2 after 20 h at 90°C by HPLC (high-performance liquid chromatography), and the most polymeric color formation was observed in the concentration of 60% sucrose at pH 2 after 60 h.

pH/redox responsive size-switchable intelligent nanovehicle for tumor microenvironment targeted DOX release.

Tumor microenvironment (TME) targeted strategy could control the drug release in tumor cells more accurately and creates a new opportunity for enhanced site-specific targeted delivery. In this study, (PAA-b-PCL-S-S-PCL-b-PAA) copolymeric nanoparticles (NPs) with size-switchable ability and dual pH/redox-triggered drug release behavior were designed to significantly promote cancer uptake (cell internalization of around 100% at 30 min) and site-specific targeted doxorubicin (DOX) delivery in MDA-MB-231 tumor cells. NPs surface charge was shifted from - 17.8 to - 2.4 and their size shrunk from 170.3 to 93 nm in TME. The cell cycle results showed that DOX-loaded NPs showed G2/M (68%) arrest, while free DOX showed sub-G1 arrest (22%). Apoptosis tests confirmed that the cells treated with DOX-loaded NPs showed a higher amount of apoptosis (71.6%) than the free DOX (49.8%). Western blot and RT-PCR assays revealed that the apoptotic genes and protein levels were significantly upregulated using the DOX-loaded NPs vs. the free DOX (Pvalue < 0.001). In conclusion, dual pH/redox-responsive and size-switchable DOX-loaded NPs developed here showed outstanding anti-tumoral features compared with free DOX that might present a prospective platform for tumor site-specific accumulation and drug release that suggest further in vivo research.

Integration of ß-cyclodextrin into graphene quantum dot nano-structure and its application towards detection of Vitamin C at physiological pH: A new electrochemical approach.

For the first time, ß-Cyclodextrin (ß-CD) attachment to graphene quantum dot (GQD) structure was performed using simultaneous electrodeposition of GQD and ß-CD on the surface of glassy carbon electrode (GCE). Cyclic voltammetry at potential range -1.0 to 1.0V from mixture of GQD and ß-CD produced a well-defined ß-CD-GQD deposited on the surface of glassy carbon electrode. ß-CD-GQD modified GCE was used as a new electrocatalytical nanocomposite towards electrooxidation of Vitamin C (as sample analyte). The synergistic effects and the catalytic activity of the ß-CD-GQD modified GCE were investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV) chronoamperometry (CA) and square wave voltammetry (SWV). The process of oxidation involved and its kinetics were established by using cyclic voltammetry, chronoamperometry techniques. It has been found that in the course of an anodic potential sweep the electro-oxidation of Vitamin C is catalyzed by synergetic effect of ß-CD and GQD through a mediated electron transfer mechanism. Therefore, ß-CD-GQDs promote the rate of oxidation by increasing the peak current. The cyclic voltammetric results indicate that ß-CD-GQDs-GCE can remarkably enhance electroactivity towards the oxidation of Vitamin C in buffer solution. We have illustrated that the as-obtained ß-CD-GQDs-GCE exhibited a much higher electrocatalytical behavior than GQDs for the electrooxidation and detection of Vitamin C which was about two fold higher than for GQDs. The electrochemical behavior was further exploited as detection scheme for the Vitamin C electrooxidation by square wave voltammetry.