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Adjuvant-aided combination chemotherapy is one of the most effective ways of cancer treatment by overcoming the multidrug resistance (MDR) and reducing the side-effects of anticancer drugs. In this study, Conferone (Conf) was used as an adjuvant in combination with Doxorubicin (Dox) for inducing apoptosis to MDA-MB-231 cells. Herein, the novel biodegradable amphiphilic β-cyclodextrin grafted poly maleate-co-PLGA was synthesized by thiol-ene addition and ring-opening process. Micelles obtained from the novel copolymer showed exceptional properties such as small size of around 34.5 nm, CMC of 0.1 μg/mL, and cell internalization of around 100% at 30 min. These novel engineered micelles were used for combination delivery of doxorubicin-conferone with high encapsulation efficiency of near 100% for both drugs. Our results show that combination delivery of Dox and Conf to MDA-MB-231 cells had synergistic effects (CI IC50 = 0.259 μg/mL). RT-PCR and western-blot tests show that Dox-Conf loaded βCD-g-PMA-co-PLGA micelle induced apoptosis via intrinsic pathway. Therefore, the unique design of multi-functional pH-sensitive micelles open a new perspective for the development of nanomedicine for combination chemo-adjuvant therapy against malignant cancer.

pH-sensitive micelles are desirable for co-drug delivery in cancer chemotherapy. Herein, a novel, very pH-sensitive and biodegradable citric acid grafted poly maleate-block-poly lactic-co-glycolic acid was synthesized and assembled as micelles via ultrasonication. The engineered homogeneous nanomicelles were used for the first time for doxorubicin and conferone combination chemotherapy in the MDA-MB-231 breast cancer cell line. The physicochemical properties of the micelles were investigated via 13CNMR, 1HNMR, FTIR, CHNS, DSC, SEM, and DLS-zeta analysis, and the in vitro degradation of the synthetic copolymer was investigated to confirm its biodegradability. The critical micelle concentration (CMC) value of the micelles was determined using pyrene as a probe and a spectrofluorometer. The drug release process was studied in acidic and neutral pH. The anti-tumoral properties of the dual drug-loaded micelles were investigated via MTT assay, cell cycle, and apoptosis experiments. The apoptosis was confirmed by Annexin-V, qRT-PCR and western blotting. The particle size (51.9 nm), zeta potential (−6.57 mV) and CMC (1.793 μg mL−1) of the co-drug loaded micelles were in the acceptable range for electrostatic stability. The uptake of the co-drug loaded micelles in the MDA-MB-231 cell line and spheroids was 97% and 36.1%, respectively. The cell cycle and apoptosis tests revealed that the cells treated with the co-drug-loaded micelles showed the highest amount of apoptosis (95.35%) in comparison to the single drug-loaded micelles and free drugs. Reverse transcription PCR (RT-PCR) showed that the expression levels of the proapoptotic genes were significantly up-regulated in the presence of the co-drug loaded micelles versus the single-drug loaded micelles and free drugs. Western blotting revealed that the co-drug-loaded micelles promoted apoptosis via the caspase-dependent pathway. Our findings confirmed that the pH-responsive biodegradable micelles containing doxorubicin and conferone are novel and effective for combination chemotherapy and offer a promising strategy for future in vivo studies.

This study aimed to design an effective targeted combination of doxorubicin (Dox)-Curcumin (Cur) delivery system to eradicate the MDA-MB231 cell line. A novel biodegradable poly e-Caprolactone-co-maleic anhydride-graft-citric acid copolymer micelle (PCL-co-P(MA-g-CA)) was synthesized through thiolen radical copolymerization and ring-opening polymerization. The unique micelle structure allowed simultaneous loading of hydrophilic Dox and hydrophobic Cur with a loading efficiency of above 98 % for each drug. The physicochemical characterization of copolymeric micelle was analyzed by 1HNMR, 13CNMR, FTIR, DSC, CMC, DLS and SEM. The in vitro cytotoxicity was assessed by MTT assay, cell cycle analysis, annexin V-FITC apoptosis, qRT-PCR and western blot. The final obtained micelles with critical micelle concentration (CMC) of 0.5 μg/mL, and particle size and surface charge was 60 nm and -14.1 mV, respectively. Beside the fast uptake of designed micelle, Dox@Cur loaded micelle showed a synergistic effect with the combination index (CI) value of below 1. Our results revealed that this novel engineered combinatorial micelle induced apoptosis (96 %) which was proved by annexin V and cell cycle. qRT-PCR and western blot assays demonstrated involvement of intrinsic apoptosis pathways in the genetic and protein levels. Finally, the penetration of Dox@Cur loaded micelle was evaluated by 3D in vitro tumor formation. Our findings showed the penetration behavior of micelles is in a concentration-dependent manner. In conclusion, combinational therapy by using Dox and Cur nano-formulation has boosted the cytotoxicity in MDA-MB231 cells by promoting the apoptotic response.

This paper describes the adsorption of heavy metal ions from aqueous solutions by nano structure alumina. Our study tested the removal of three heavy metals: Pb 2+ , Ni 2+ and Zn 2+ . The optimum contact time, adsorbent mass, and pH were determined, and adsorption isotherms were obtained using concentrations of the metal ions ranging from 25 to 150 mg L − 1 . The adsorption process follows pseudo-second-order reaction kinetics, as well as Langmuir and Freundlich adsorption isotherms. The paper discusses the thermodynamic parameters of the adsorption (the Gibbs free energy, entropy, and enthalpy). Our results demonstrate that the adsorption process was spontaneous and exothermic under natural conditions. The maximum capacity of adsorbent for Pb 2+ , Ni 2+ and Zn 2+ are 125, 83.33 and 58.82 mg g − 1 , respectively. This study revealed that nano structure γ-alumina was an effective adsorbent for removal of these ions from aqueous solutions.