scholarly journals Oxidation-Triggerable Liposome Incorporating Poly(Hydroxyethyl Acrylate-co-Allyl methyl sulfide) as an Anticancer Carrier of Doxorubicin

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 180 ◽  
Author(s):  
Jin Ah Kim ◽  
Dong Youl Yoon ◽  
Jin-Chul Kim
Keyword(s):  
Cancer Cells ◽  
Surface Activity ◽  
Laser Scanning ◽  
Drug Carriers ◽  
Laser Scanning Microscopy ◽  
Cancer Drug ◽  
Confocal Laser ◽  
H2o2 Treatment ◽  
Methyl Sulfide ◽  
Anti Cancer

Since cancer cells are oxidative in nature, anti-cancer agents can be delivered to cancer cells specifically without causing severe normal cell toxicity if the drug carriers are designed to be sensitive to the intrinsic characteristic. Oxidation-sensitive liposomes were developed by stabilizing dioleoylphosphatidyl ethanolamine (DOPE) bilayers with folate-conjugated poly(hydroxyethyl acrylate-co-allyl methyl sulfide) (F-P(HEA-AMS)). The copolymer, synthesized by a free radical polymerization, was surface-active but lost its surface activity after AMS unit was oxidized by H2O2 treatment. The liposomes with F-P(HEA-AMS) were sensitive to H2O2 concentration (0%, 0.5%, 1.0%, and 2.0%) in terms of release, possibly because the copolymer lost its surface activity and its bilayer-stabilizing ability upon oxidation. Fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM) revealed that doxorubicin (DOX)-loaded liposomes stabilized with folate-conjugated copolymers markedly promoted the transport of the anti-cancer drug to cancer cells. This was possible because the liposomes were readily translocated into the cancer cells via receptor-mediated endocytosis. This liposome would be applicable to the delivery carrier of anticancer drugs.

scholarly journals Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 462 ◽  
Author(s):  
Joanna Pilch ◽  
Patrycja Kowalik ◽  
Piotr Bujak ◽  
Anna M. Nowicka ◽  
Ewa Augustin
Keyword(s):  
Quantum Dots ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Laser Scanning ◽  
Biological Response ◽  
Drug Carriers ◽  
Confocal Laser ◽  
Normal Cells ◽  
H460 Cells ◽  
Hct116 Cells

Nanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry and light microscopy) in lung H460 and colon HCT116 cancer cells. We show the time-dependent cellular uptake of QD–UA hybrids, which were more efficiently retained inside the cells compared to UAs alone, especially in H460 cells, which could be due to multiple endocytosis pathways. In contrast, in HCT116 cells, the hybrids were taken up only by one endocytosis mechanism. Both UAs and their hybrids induced apoptosis in H460 and HCT116 cells (to a greater extent in H460). Cells which did not die underwent senescence more efficiently following QDs–UAs treatment, compared to UAs alone. Cellular senescence was not observed in HCT116 cells following treatment with both UAs and their hybrids. Importantly, QDgreen/red themselves did not provoke toxic responses in cancer or normal cells. In conclusion, QDs are good candidates for targeted UA delivery carriers to cancer cells while protecting normal cells from toxic drug activities.

scholarly journals Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

2018 ◽  
Vol 14 ◽  
pp. 756-771 ◽  
Author(s):  
Sabine Schuster ◽  
Beáta Biri-Kovács ◽  
Bálint Szeder ◽  
Viktor Farkas ◽  
László Buday ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Dependent Manner ◽  
Binding Studies ◽  
Gnrh Receptors

Gonadotropin releasing hormone-III (GnRH-III), a native isoform of the human GnRH isolated from sea lamprey, specifically binds to GnRH receptors on cancer cells enabling its application as targeting moieties for anticancer drugs. Recently, we reported on the identification of a novel daunorubicin–GnRH-III conjugate (GnRH-III–[4Lys(Bu), 8Lys(Dau=Aoa)] with efficient in vitro and in vivo antitumor activity. To get a deeper insight into the mechanism of action of our lead compound, the cellular uptake was followed by confocal laser scanning microscopy. Hereby, the drug daunorubicin could be visualized in different subcellular compartments by following the localization of the drug in a time-dependent manner. Colocalization studies were carried out to prove the presence of the drug in lysosomes (early stage) and on its site of action (nuclei after 10 min). Additional flow cytometry studies demonstrated that the cellular uptake of the bioconjugate was inhibited in the presence of the competitive ligand triptorelin indicating a receptor-mediated pathway. For comparative purpose, six novel daunorubicin–GnRH-III bioconjugates have been synthesized and biochemically characterized in which 6Asp was replaced by D-Asp, D-Glu and D-Trp. In addition to the analysis of the in vitro cytostatic effect and cellular uptake, receptor binding studies with 125I-triptorelin as radiotracer and degradation of the GnRH-III conjugates in the presence of rat liver lysosomal homogenate have been performed. All derivatives showed high binding affinities to GnRH receptors and displayed in vitro cytostatic effects on HT-29 and MCF-7 cancer cells with IC50 values in a low micromolar range. Moreover, we found that the release of the active drug metabolite and the cellular uptake of the bioconjugates were strongly affected by the amino acid exchange which in turn had an impact on the antitumor activity of the bioconjugates.

Doxorubicin and siRNA Co-Delivery System Based on Carbon Dots Inhibits Chemoresistance of Lung Cancer

2021 ◽  
Author(s):  
Hui Luo ◽  
Kexin Tang ◽  
Kaichen Huang ◽  
Xi Lin ◽  
Chaoming Mei ◽  
...  
Keyword(s):  
Delivery System ◽  
Carbon Dots ◽  
Laser Scanning ◽  
Raw Materials ◽  
Metastatic Potential ◽  
Laser Scanning Microscopy ◽  
Migration And Invasion ◽  
Confocal Laser ◽  
Clinical Practices ◽  
Anti Cancer

Abstract BackgroundThe resistance to the anti-cancer agent limits the chemotherapy effect in the cancer therapy. Tumor easily develops resistance to anti-cancer drugs leading to decreased therapy efficiency of chemotherapies. Targeting signaling molecules related with chemoresistance through strategy of co-delivery siRNA and chemotherapeutics may overcome the multidrug resistance to chemotherapy. A co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. ResultsThe co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics by electronstatic interactions on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property and the capability of loading siRNA. The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cell by pH-triggered manner using flow cytometry and confocal laser scanning microscopy analysis. MRP1 was successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionThe co-delivery systems effectively loaded and released siRNA and DOX agents to the targeted tumor, overcoming the resistant to chemotherapy. By suppressing MRP1, CD-PEI-DOX-siMRP1 can obviously increase the drug intercellular accumulation and inhibit the cell proliferation, migration and invasion, implying its potential application in enhancing therapeutic efficiency in clinical practices.

scholarly journals LHH1, a novel antimicrobial peptide with anti-cancer cell activity identified from Lactobacillus casei HZ1

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jun-Fang He ◽  
Du-Xin Jin ◽  
Xue-Gang Luo ◽  
Tong-Cun Zhang
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lactobacillus Casei ◽  
Laser Scanning ◽  
Cell Activity ◽  
Antimicrobial Activities ◽  
Confocal Laser ◽  
Anti Cancer

Abstract Antimicrobial peptides have been attracting increasing attention for their multiple beneficial effects. In present study, a novel AMP with a molecular weight of 1875.5 Da, was identified from the genome of Lactobacillus casei HZ1. The peptide, which was named as LHH1 was comprised of 16 amino acid residues, and its α-helix content was 95.34% when dissolved in 30 mM SDS. LHH1 exhibited a broad range of antimicrobial activities against Gram-positive bacteria and fungus. It could effectively inhibit Staphylococcus aureus with a minimum inhibitory concentration of 3.5 μM and showed a low hemolytic activity. The scanning electron microscope, confocal laser scanning microscope and flow cytometry results showed that LHH1 exerted its antibacterial activity by damaging the cell membrane of Staphylococcus aureus. Meanwhile, LHH1 also exhibited anti-cancer cell activities against several cancer cells via breaking the cell membrane of MGC803, HCT116 and C666-1 cancer cells.

FAP-1 in pancreatic cancer cells

2001 ◽  
Vol 114 (15) ◽  
pp. 2735-2746
Author(s):  
Hendrik Ungefroren ◽  
Marie-Luise Kruse ◽  
Anna Trauzold ◽  
Stefanie Roeschmann ◽  
Christian Roeder ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Surface ◽  
Pancreatic Carcinoma ◽  
Cancer Cells ◽  
Golgi Complex ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Pancreatic Cancer Cells ◽  
Induced Apoptosis

In this study we investigated the functional role of FAP-1 as a potential inhibitor of CD95 (Fas, APO-1)-mediated apoptosis in pancreatic cancer cells. Stable transfection of the CD95-sensitive, FAP-1-negative cell line Capan-1 with an FAP-1 cDNA resulted in a strongly decreased sensitivity to CD95-induced apoptosis, as measured by DNA fragmentation and caspase-3 activity. Inhibition of cellular protein tyrosine phosphatases with orthovanadate dose-dependently increased CD95-induced apoptosis in CD95-resistant FAP-1-positive Panc89 and Capan-1-FAP-1 cells almost to the level seen in wild-type Capan-1 cells. Blocking the CD95/FAP-1 interaction in Panc89 cells by cytoplasmic microinjection of a synthetic tripeptide mimicking the C terminus of CD95 resulted in a mean 5.5-fold increase in apoptosis compared to cells that received a control peptide. Using confocal laser scanning microscopy we show that in Panc89 cells FAP-1 is mainly associated with the Golgi complex and with peripheral vesicles. FAP-1 displayed enhanced colocalization with CD95 upon CD95 stimulation in the Golgi complex but not in surface-associated vesicles. This correlated with a decrease in plasma membrane staining for CD95 as determined by FACS analysis. Inhibition of Golgi anterograde transport by brefeldin A abolished the anti-CD95-induced colocalization of FAP-1 and CD95 as well as the decrease in cell-surface-associated CD95. Finally, we demonstrate by immunohistochemistry that FAP-1 is strongly expressed in tumor cells from pancreatic carcinoma tissues. Taken together, these results show that FAP-1 can protect pancreatic carcinoma cells from CD95-mediated apoptosis, probably by preventing anti-CD95-induced translocation of CD95 from intracellular stores to the cell surface.

scholarly journals Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen

Polymers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1516
Author(s):  
Munther Alomari ◽  
Rabindran Jermy Balasamy ◽  
Dana Almohazey ◽  
Vijaya Ravinayagam ◽  
Mohammad Al Hamad ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Methyl Methacrylate ◽  
Cancer Cells ◽  
Laser Scanning ◽  
Nile Red ◽  
Laser Scanning Microscopy ◽  
Estrogen Signaling ◽  
Confocal Laser ◽  
Poly Methyl Methacrylate ◽  
Cervical Cancer Cells

Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will not uptake TAM and will show low response. Poly (methyl methacrylate) (PMMA) nanoparticles were prepared using surfactant-free emulsion polymerization, then were loaded with Nile red (NR), which resulted in PMMA-NR. To enhance TAM delivery to cervical cancer cells (HELA), which is considered ER-negative, we loaded TAM and polymethyl methacrylate nanoparticles-Nile-red into silica (PMMA-NR-Si-TAM). The uptake and intracellular distribution were visualized by confocal laser scanning microscopy, and the in vitro cytotoxic activity was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay using HELA and non-tumorigenic cell line HFF-1. The sensitivity of HELA (LC50: 207.31 µg/mL) and HFF-1 (LC50: 234.08 µg/mL) to free TAM was very low. However, after the encapsulation of TAM with PMMA-NR, the sensitivity significantly increased HELA (LC50: 71.83 µg/mL) and HFF-1 (LC50: 37.36 µg/mL). This indicates that TAM can be used for the treatment of ER-negative cervical cancer once conjugated to PMMA-NR nanoparticles. In addition, the PMMA-NR formulation appears to be highly suitable for cancer imaging and drug delivery.

scholarly journals Optical Properties of Doxorubicin Hydrochloride Load and Release on Silica Nanoparticle Platform

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3968
Author(s):  
Trong Nghia Nguyen ◽  
Thi Thuy Nguyen ◽  
Thi Ha Lien Nghiem ◽  
Duc Toan Nguyen ◽  
Thi Thu Ha Tran ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Laser Scanning ◽  
Ph Dependence ◽  
Silica Nanoparticle ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Doxorubicin Hydrochloride ◽  
Drug Delivery Vehicles ◽  
The Stöber Method

Silica nanoparticles (SiO2 NPs) synthesized by the Stober method were used as drug delivery vehicles. Doxorubicin hydrochloride (DOX·HCl) is a chemo-drug absorbed onto the SiO2 NPs surfaces. The DOX·HCl loading onto and release from the SiO2 NPs was monitored via UV-VIS and fluorescence spectra. Alternatively, the zeta potential was also used to monitor and evaluate the DOX·HCl loading process. The results showed that nearly 98% of DOX·HCl was effectively loaded onto the SiO2 NPs’ surfaces by electrostatic interaction. The pH-dependence of the process wherein DOX·HCl release out of DOX·HCl-SiO2 NPs was investigated as well. For comparison, both the free DOX·HCl molecules and DOX·HCl-SiO2 NPs were used as the labels for cultured cancer cells. Confocal laser scanning microscopy images showed that the DOX·HCl-SiO2 NPs were better delivered to cancer cells which are more acidic than healthy cells. We propose that engineered DOX·HCl-SiO2 systems are good candidates for drug delivery and clinical applications.

scholarly journals Aptamer-Aptamer Chimera for Targeted Delivery and ATP-Responsive Release of Doxorubicin into Cancer Cells

2021 ◽  
Vol 22 (23) ◽  
pp. 12940
Author(s):  
Ezaldeen Esawi ◽  
Walhan Alshaer ◽  
Ismail Sami Mahmoud ◽  
Dana A. Alqudah ◽  
Bilal Azab ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Targeted Delivery ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Innovative Drug ◽  
Great Opportunity ◽  
Selective Delivery ◽  
In Cells

Aptamers offer a great opportunity to develop innovative drug delivery systems that can deliver cargos specifically into targeted cells. In this study, a chimera consisting of two aptamers was developed to deliver doxorubicin into cancer cells and release the drug in cytoplasm in response to adenosine-5′-triphosphate (ATP) binding. The chimera was composed of the AS1411 anti-nucleolin aptamer for cancer cell targeting and the ATP aptamer for loading and triggering the release of doxorubicin in cells. The chimera was first produced by hybridizing the ATP aptamer with its complementary DNA sequence, which is linked with the AS1411 aptamer via a poly-thymine linker. Doxorubicin was then loaded inside the hybridized DNA region of the chimera. Our results show that the AS1411–ATP aptamer chimera was able to release loaded doxorubicin in cells in response to ATP. In addition, selective uptake of the chimera into cancer cells was demonstrated using flow cytometry. Furthermore, confocal laser scanning microscopy showed the successful delivery of the doxorubicin loaded in chimeras to the nuclei of targeted cells. Moreover, the doxorubicin-loaded chimeras effectively inhibited the growth of cancer cell lines and reduced the cytotoxic effect on the normal cells. Overall, the results of this study show that the AS1411–ATP aptamer chimera could be used as an innovative approach for the selective delivery of doxorubicin to cancer cells, which may improve the therapeutic potency and decrease the off-target cytotoxicity of doxorubicin.

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