Micelle-in-Liposomes for Sustained Delivery of Anticancer Agents That Promote Potent TRAIL-Induced Cancer Cell Apoptosis

Zhang, Zhenjiang; Patel, Sagar B.; King, Michael R.

doi:10.3390/molecules26010157

Cited by 15 publications

(9 citation statements)

References 41 publications

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“…We have adopted the double staining technique to establish the apoptotic potential of the blank micelles, free 2 ME, and the formulated 2 ME-loaded mixed micelles in PC-3 cell line. In brief, the PC-3 cells were exposed to the samples in a 12-well plate, where the initial density of the seeded cells was maintained at 10 5 cells per well (Zhang et al, 2020). IC50 concentration of 2 ME was maintained in the wells, which were incubated at 37°C for 24 h. Thereafter, the cells were washed with phosphate buffer in order to remove the micelles and free drug from the wells, and the apoptotic potential of the agents was measured using the conjugate of Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide following the instruction provided with the apoptotic detection kit (BD Bioscience, United States).…”

Section: Apoptotic Assaymentioning

confidence: 99%

Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer

et al. 2021

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The therapeutic efficacy of antineoplastic agents possessing a selective target to the nucleus of the cancer cells could be enhanced through novel formulation approaches. Thus, toward the improvement of the anticancer potential of 2-methoxy estradiol (2 ME) on prostate cancer, the drug was entrapped into the hydrophobic micelles core formulated with Phospholipon 90G and d-α-tocopheryl polyethylene glycol succinate (TPGS). Optimization of the formulation was done by Box-Behnken statistical design using Statgraphics software to standardize percentages of TPGS and phospholipid to obtain the smallest particle size. The optimized formulation was found to be spherical with nanometer size of 152 ± 5.2 nm, and low PDI (0.234). The entrapment efficiency of the micelles was 88.67 ± 3.21% with >93% release of 2 ME within 24 h. There was a 16-fold increase in apoptosis and an 8-fold increase in necrosis of the PC-3 cells when incubated with 2 ME micellar delivery compared to control cells (2.8 ± 0.2%). This increased apoptosis was further correlated with increased BAX expression (11.6 ± 0.7) and decreased BCL-2 expression (0.29 ± 0.05) in 2 ME micelles treated cells when compared to the control group. Further, loss of mitochondrial membrane potential (∼50-fold) by the drug-loaded micelles and free drug compared to control cells was found to be due to the generation of ROS. Findings on cell cycle analysis revealed the significant arrest of the G2-M phase of the PC-3 cells when incubated with the optimized formulation. Simultaneously, a significantly increased number of cells in pre-G1 revealed the maximum apoptotic potential of the drug when delivered via micellar formulation. Finally, upregulation of caspase-9, p53, and NO, with downregulation of TNF-α, NF-κβ, and inflammatory mediators of the PC-3 cells established the superiority of the micellar approach against prostate cancer. In summary, the acquired results highlighted the potentiality of the 2 ME-micellar delivery tool for controlling the growth of prostate cancer cells for improved efficacy.

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Section: Apoptotic Assaymentioning

confidence: 99%

Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer

et al. 2021

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“…In brief, MCF-7 cells were exposed to samples in a 12-well plate, where the initial density of the seed cells was preserved at 10 5 cells per well. (Zhang et al, 2020). A 10 μM concentration of 2 ME was maintained in the wells, which were incubated at 37°C for 24 h. Thereafter, the cells were washed with phosphate buffer in order to remove the micelles and free drug from the wells, and the apoptotic potential of the agents was measured using the conjugate of Annexin Vfluorescein isothiocyanate (FITC) and propidium iodide following the instruction provided with the apoptotic detection kit (BD Bioscience, USA).…”

Section: Evaluation Of 2 Me -Ala Npsmentioning

confidence: 99%

2-Methoxy-estradiol Loaded Alpha Lipoic Acid Nanoparticles Augment Cytotoxicity in MCF-7 Breast Cancer Cells

et al. 2021

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The therapeutic effectiveness of anticancer drugs with a selective target for the nucleus of cancer cells may be improved by experimental approaches. In this regard, the formulation of anticancer drugs is considered one of the best ways to improve their effectiveness in targeting cancerous tissues. To enhance the anticancer activity of 2-methoxy-estradiol (2 ME) for breast cancer, 2-methoxyestradiol loaded alpha lipoic acid nanoparticles have been formulated. The prepared formula was observed to be spherical with a nanometer-scale and low PDI size (.234). The entrapment efficiency of the 2ME-ALA NPs was 87.32 ± 2.21% with > 85% release of 2 ME within 24 h. There was a 1.2-fold increase in apoptosis and a 3.46-fold increase in necrosis of the MCF-7 cells when incubated with 2ME-ALA NPs when compared to control cells. This increased apoptosis was also associated with increased ROS and increased p53 expression in 2ME-ALA NPs treated cells compared to the raw-2 ME group. Evaluation of cell-cycle data showed a substantial arrest of the G2-M phase of the MCF-7 cells when incubated with 2ME-ALA NPs. At the same time, a dramatically increased number of pre-G1 cells showed the increased apoptotic potential of the 2 ME when administered via the proposed formulation. In the end, the differential upregulation of caspase-3, p53, and ROS in MCF-7 cells established the superiority of the 2ME-ALA-Ms approach in targeting breast cancer. In summary, these results demonstrate that 2ME-ALA NPs are an efficient delivery tool for controlling the growth of breast cancer cells.

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“…The increase in drug resistance in leukemic cells in high-density cultures was marked earlier [ 50 , 51 ]; however, the mechanism of this phenomena remains unclear. The results of our work show the great increase in the resistance of different AML cells (lines HL-60, THP-1, MV411, U937) in high-density cultures to inhibitors of topoisomerases, etoposide and topotecan [ 52 , 53 ]; an antimetabolite, cytarabine [ 54 ]; DNA targeting antitumor drugs doxorubicin and cisplatin [ 55 , 56 , 57 ]; as well as to antitumor recombinant protein izTRAIL [ 58 ]. It was important that the increase in the drug resistance of AML cells in high-density cell culture was reversible and that the transfer of the AML cells from high-density to low-density cultures decreased the resistance to an initial state.…”

Section: Discussionmentioning

confidence: 99%

The Increase in the Drug Resistance of Acute Myeloid Leukemia THP-1 Cells in High-Density Cell Culture Is Associated with Inflammatory-like Activation and Anti-Apoptotic Bcl-2 Proteins

Kobyakova

Lomovskaya

Сенотов

et al. 2022

IJMS

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It is known that cell culture density can modulate the drug resistance of acute myeloid leukemia (AML) cells. In this work, we studied the drug sensitivity of AML cells in high-density cell cultures (cell lines THP-1, HL-60, MV4-11, and U937). It was shown that the AML cells in high-density cell cultures in vitro were significantly more resistant to DNA-damaging drugs and recombinant ligand izTRAIL than those in low-density cell cultures. To elucidate the mechanism of the increased drug resistance of AML cells in high-density cell cultures, we studied the activation of Bcl-2, Hif-1alpha, and NF-kB proteins, as well as cytokine secretion, the inflammatory immunophenotype, and the transcriptome for THP-1 cells in the low-density and high-density cultures. The results indicated that the increase in the drug resistance of proliferating THP-1 cells in high-density cell cultures was associated with the accumulation of inflammatory cytokines in extracellular medium, and the formation of NF-kB-dependent inflammatory-like cell activation with the anti-apoptotic proteins Bcl-2 and Bcl-xl. The increased drug resistance of THP-1 cells in high-density cultures can be reduced by ABT-737, an inhibitor of Bcl-2 family proteins, and by inhibitors of NF-kB. The results suggest a mechanism for increasing the drug resistance of AML cells in the bone marrow and are of interest for developing a strategy to suppress this resistance.

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Micelle-in-Liposomes for Sustained Delivery of Anticancer Agents That Promote Potent TRAIL-Induced Cancer Cell Apoptosis

Cited by 15 publications

References 41 publications

Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer

Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer

2-Methoxy-estradiol Loaded Alpha Lipoic Acid Nanoparticles Augment Cytotoxicity in MCF-7 Breast Cancer Cells

The Increase in the Drug Resistance of Acute Myeloid Leukemia THP-1 Cells in High-Density Cell Culture Is Associated with Inflammatory-like Activation and Anti-Apoptotic Bcl-2 Proteins

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