scholarly journals Polyphosphazene-Based Nanocarriers for the Release of Camptothecin and Epirubicin

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 169
Author(s):  
Javier Pérez Quiñones ◽  
Cornelia Roschger ◽  
Aitziber Iturmendi ◽  
Helena Henke ◽  
Andreas Zierer ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Cancer Cell Line ◽  
Fold Increase ◽  
Lung Fibroblasts ◽  
Selective Toxicity ◽  
M Phase ◽  
Linear Poly ◽  
Almost All ◽  
Mcf 7

The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term activity and reduced side effects. In this sense, polyphosphazene nanocarriers were synthesized for the sustained release of the anticancer drugs camptothecin (CPT) and epirubicin (EPI). Linear poly(dichloro)phosphazene was modified with lipophilic tocopherol or testosterone glycinate, with antioxidant and antitumor activity, and with hydrophilic Jeffamine M1000 to obtain different polyphosphazene nanocarriers. It allowed us to encapsulate the lipophilic CPT and the more hydrophilic EPI. The encapsulation process was carried out via solvent exchange/precipitation, attaining a 9.2–13.6 wt% of CPT and 0.3–2.4 wt% of EPI. CPT-loaded polyphosphazenes formed 140–200 nm aggregates in simulated body physiological conditions (PBS, pH 7.4), resulting in an 80–100-fold increase of CPT solubility. EPI-loaded polyphosphazenes formed 250 nm aggregates in an aqueous medium. CPT and EPI release (PBS, pH 7.4, 37 °C) was monitored for 202 h, being almost linear during the first 8 h. The slow release of testosterone and tocopherol was also sustained for 150 hours in PBS (pH 7.4 and 6.0) at 37 °C. The co-delivery of testosterone or tocopherol and the anticancer drugs from the nanocarriers was expected. Cells of the human breast cancer cell line MCF-7 demonstrated good uptake of anticancer-drug-loaded nanocarriers after 6 hours. Similarly, MCF-7 spheroids showed good uptake of the anticancer-drug-loaded aggregates after 72 hours. Almost all anticancer-drug-loaded polyphosphazenes exhibited similar or superior toxicity against MCF-7 cells and spheroids when compared to raw anticancer drugs. Additionally, cell-cycle arrest in the G2/M phase was increased in response to the drug-loaded nanocarriers. Almost no toxicity of anticancer-drug-loaded aggregates against primary human lung fibroblasts was observed. Furthermore, the aggregates displayed no hemolytic activity, which is in contrast to the parent anticancer drugs. Consequently, synthesized polyphosphazene-based nanocarriers might be potential nanomedicines for chemotherapy.

scholarly journals Design, Synthesis and Biological Evaluation of Morpholinated Isatin-Quinoline Hybrids as Potential Anti-Breast Cancer Agents.

2021 ◽  
Author(s):  
Atamjit Singh ◽  
Komalpreet Kaur ◽  
Jaspreet Kaur ◽  
Puja Gulati ◽  
Amit Duggal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor Alpha ◽  
Fibroblast Cell ◽  
Biological Evaluation ◽  
Breast Cancer Cell Lines ◽  
Design Synthesis ◽  
M Phase ◽  
Almost All ◽  
Morpholine Derivatives ◽  
Mcf 7

Abstract Keeping in view the emerging need of potent and safer anti-breast cancer agents as well as pharmacological attributes of isatin, quinoline and morpholine derivatives, novel hydrazone linked morpholinated isatin-quinoline hybrids has been designed, synthesized and evaluated as anti-breast cancer agents. Synthesized hybrid compounds were preliminary screened against two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all synthetics showed potent inhibitory potential against hormone positive MCF-7 cells while inactive against hormone negative MDA-MB-231 cells. Potent compounds were further evaluated against L929 (noncancerous skin fibroblast) cell line and found highly selective for MCF-7 cells over L929 cells. Cell cycle analysis confirmed that most potent compound AS-4 (MCF-7: GI50 = 4.36 µM) cause mitotic arrest at G2/M-phase. Due to higher selectivity toward estrogen receptor alpha (ERα) dependent MCF-7 cells various binding interactions of AS-4 with ERα are also streamlined, suggesting the capability of AS-4 in completely blocking ERα. Overall study suggest that, AS-4 can act as a potential lead for further development of potent and safer anti-breast cancer agents.

scholarly journals Marine-Inspired Bis-indoles Possessing Antiproliferative Activity against Breast Cancer; Design, Synthesis, and Biological Evaluation

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 190 ◽  
Author(s):  
Wagdy M. Eldehna ◽  
Ghada S. Hassan ◽  
Sara T. Al-Rashood ◽  
Hamad M. Alkahtani ◽  
Abdulrahman A. Almehizia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Annexin V ◽  
Fold Increase ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Lead Compounds ◽  
M Phase ◽  
Indole Series ◽  
Induced Apoptosis ◽  
Mcf 7

Diverse indoles and bis-indoles extracted from marine sources have been identified as promising anticancer leads. Herein, we designed and synthesized novel bis-indole series 7a–f and 9a–h as Topsentin and Nortopsentin analogs. Our design is based on replacing the heterocyclic spacer in the natural leads by a more flexible hydrazide linker while sparing the two peripheral indole rings. All the synthesized bis-indoles were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. The most potent congeners 7e and 9a against MCF-7 cells (IC50 = 0.44 ± 0.01 and 1.28 ± 0.04 μM, respectively) induced apoptosis in MCF-7 cells (23.7-, and 16.8-fold increase in the total apoptosis percentage) as evident by the externalization of plasma membrane phosphatidylserine detected by Annexin V-FITC/PI assay. This evidence was supported by the Bax/Bcl-2 ratio augmentation (18.65- and 11.1-fold compared to control) with a concomitant increase in the level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action. The obtained results (% inhibition range: 16%–58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. Collectively, these results suggested that herein reported bis-indoles are good lead compounds for further optimization and development as potential efficient anti-breast cancer drugs.

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

Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110550
Author(s):  
Nabil A. Alhakamy ◽  
Mohammed W. Al-Rabia ◽  
Hani Z. Asfour ◽  
Samah Alshehri ◽  
Waleed S. Alharbi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Lipoic Acid ◽  
Breast Cancer Cells ◽  
Entrapment Efficiency ◽  
Fold Increase ◽  
Alpha Lipoic Acid ◽  
P53 Expression ◽  
Mcf 7

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.

scholarly journals In Vitro Anticancer Drug Sensitivity Sensing through Single-Cell Raman Spectroscopy

Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 286
Author(s):  
Jingkai Wang ◽  
Kaicheng Lin ◽  
Huijie Hu ◽  
Xingwang Qie ◽  
Wei E. Huang ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Line ◽  
Anticancer Drugs ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Metabolic Activity ◽  
Drug Sensitivity ◽  
Cancer Cell Line ◽  
Sensitivity Testing

Traditional in vitro anticancer drug sensitivity testing at the population level suffers from lengthy procedures and high false positive rates. To overcome these defects, we built a confocal Raman microscopy sensing system and proposed a single-cell approach via Raman-deuterium isotope probing (Raman-DIP) as a rapid and reliable in vitro drug efficacy evaluation method. Raman-DIP detected the incorporation of deuterium into the cell, which correlated with the metabolic activity of the cell. The human non-small cell lung cancer cell line HCC827 and human breast cancer cell line MCF-7 were tested against eight different anticancer drugs. The metabolic activity of cancer cells could be detected as early as 12 h, independent of cell growth. Incubation of cells in 30% heavy water (D2O) did not show any negative effect on cell viability. Compared with traditional methods, Raman-DIP could accurately determine the drug effect, meanwhile, it could reduce the testing period from 72–144 h to 48 h. Moreover, the heterogeneity of cells responding to anticancer drugs was observed at the single-cell level. This proof-of-concept study demonstrated the potential of Raman-DIP to be a reliable tool for cancer drug discovery and drug susceptibility testing.

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