Novel Targeted Anti-Tumor Nanoparticles Developed from Folic Acid-Modified 2-Deoxyglucose

The glucose analog, 2-deoxyglucose (2-DG), specifically inhibits glycolysis of cancer cells and interferes with the growth of cancer cells. However, the excellent water solubility of 2-DG makes it difficult to be concentrated in tumor cells. In this study, a targeted nano-pharmacosome was developed with folic acid-modified 2-DG (FA-2-DG) by using amino ethanol as a cleavable linker. FA-2-DG was able to self-assemble, forming nano-particles with diameters of 10–30 nm. The biological effects were evaluated with cell viability assays and flow cytometry analysis. Compared with a physical mixture of folic acid and 2-DG, FA-2-DG clearly reduced cell viability and resulted in cell cycle arrest. A computational study involving docking simulation suggested that FA-2-DG can dock into the same receptor as folic acid, thus confirming that the structural modification did not affect the targeting performance. The results indicated that the nano-pharmacosome consisting of FA-2-DG can be used for targeting in a nano-drug delivery system.

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(3,3’-Methylene)bis-2-hydroxy-1,4-naphthoquinones induce cytotoxicity against DU145 and PC3 cancer cells by inhibiting cell viability and promoting cell cycle arrest

Molecular Biology Reports ◽

10.1007/s11033-021-06406-w ◽

2021 ◽

Author(s):

Paula Priscilla de Freitas ◽

Ruan Carlos Busquet Ribeiro ◽

Isabella dos Santos Guimarães ◽

Caroline S. Moreira ◽

David R. Rocha ◽

...

Keyword(s):

Cell Cycle ◽

Cell Viability ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Cycle Arrest

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Gold nanoparticle-enhanced near infrared fluorescent nanocomposites for targeted bio-imaging

RSC Advances ◽

10.1039/c4ra12066c ◽

2015 ◽

Vol 5 (1) ◽

pp. 20-26 ◽

Cited By ~ 22

Author(s):

Hao Cheng ◽

Chuanxi Wang ◽

Zhenzhu Xu ◽

Huihui Lin ◽

Chi Zhang

Keyword(s):

Folic Acid ◽

Cancer Cells ◽

Gold Nanoparticle ◽

Near Infrared ◽

Water Solubility ◽

Imaging Agents ◽

Nir Fluorescence ◽

Target Imaging ◽

Bio Imaging ◽

Low Toxicity

Folic acid-conjugated nanocomposites with NIR fluorescence, water-solubility, and low toxicity are prepared and used as target-imaging agents for cancer cells.

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2-Deoxyglucose-Modified Folate Derivative: Self-Assembling Nanoparticle Able to Load Cisplatin

Molecules ◽

10.3390/molecules24061084 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1084 ◽

Cited By ~ 1

Author(s):

Shaoming Jin ◽

Zhongyao Du ◽

Pengjie Wang ◽

Huiyuan Guo ◽

Hao Zhang ◽

...

Keyword(s):

Folic Acid ◽

Self Assembly ◽

Water Solubility ◽

Pure Water ◽

The Self ◽

Molar Ratio ◽

Antineoplastic Drugs ◽

Self Assembling ◽

Bonding Interaction ◽

Nano Drug Delivery

Folic acid has been widely introduced into nano-drug delivery systems to give nanoparticle-targeted characteristics. However, the poor water solubility of folic acid may hinder the exploitation of its ability to load antineoplastic drugs. In the present study, we designed a new folate derivative (FA-2-DG) synthesized from folic acid and 2-Deoxyglucose (2-DG). The aim of this study was to evaluate the self-assembly characteristics of FA-2-DG, and its ability of loading cisplatin. The critical micelle concentration was 7.94 × 10−6 mol L−1. Fourier transform infrared spectroscopy indicated that hydrogen bonding interaction is a main driving force for the self–assembly of FA-2-DG. The particle was stable in pure water or 0.5% bovine serum albumin dispersions. By forming a coordination bond, the particles assembled from FA-2-DG can load cisplatin. The loading efficiency was maximal when the molar ratio of FA-2-DG to cisplatin was 2:1.

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NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis

10.21203/rs.2.20090/v2 ◽

2020 ◽

Author(s):

Fenhong Kang ◽

Yanlong Wang ◽

Yaping Luo ◽

Yongjun Zhang

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Apoptosis ◽

Colony Formation ◽

G1 Phase ◽

Ovarian Cancer Cells ◽

Cycle Arrest

Abstract Background: The cancer cell metastasis and the acquisition of chemotherapy resistance remain huge challenge for ovarian cancer treatment. Previously, N-myc downstream-regulated gene 2 (NDRG2) serves as a tumor suppressor for many cancers. Here, we attempted to investigate the specific roles of NDRG2 in ovarian cancer. Methods: The expression levels of NDRG2 were detected by qRT-PCR or Immunoblotting. CCK-8 assay was employed to examine the cell viability of ovarian cancer cells. The colony formation ability was determined by colony formation assay. Flow cytometry analyses were performed to detect the cell apoptosis and cell cycle. Xenograft tumor assay was performed to detect the in vivo function of NDRG2. Results: We revealed that NDRG2 mRNA expression and protein levels were downregulated within both ovarian cancer tissues and cell lines. The overexpression of NDRG2 dramatically inhibited the cell viability and colony formation and tumor growth, whereas promoted the cell apoptosis, cell cycle arrest in G1 phase within ovarian cancer cells. More importantly, NDRG2 overexpression significantly enhanced the suppressive roles of cisplatin (DDP) in ovarian cancer cell viability. On the contrary, NDRG2 silence exerted opposing effects on ovarian cancer cells. Conclusions: In summary, we provide a solid experimental basis demonstrating the tumor-suppressive effects of NDRG2 in inhibiting the cell proliferation, enhancing the cell apoptosis, eliciting the cell cycle arrest in G1 phase, and promoting the suppressive effects of DDP on the viability of ovarian cancer cells. NDRG2 administration presents a potent adjuvant treatment for ovarian cancer therapy.

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Folate-targeted PTEN/AKT/P53 signaling pathway promotes apoptosis in breast cancer cells

Pteridines ◽

10.1515/pteridines-2020-0020 ◽

2020 ◽

Vol 31 (1) ◽

pp. 158-164

Author(s):

Hexian Wang ◽

Qiang Fan ◽

Longlong Zhang ◽

Danli Shi ◽

Haibo Wang ◽

...

Keyword(s):

Breast Cancer ◽

Folic Acid ◽

Cell Viability ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

P53 Protein ◽

Specific Inhibitor ◽

P53 Signaling ◽

P53 Signaling Pathway

AbstractObjective Folate deficiency is closely related to the occurrence of human tumors and plays an important role in cell growth, differentiation, repair, and host defense. We studied the effects of folic acid on the apoptosis of breast cancer cells (MDA-MB-231) and on the activity of the PTEN/AKT/P53 signaling pathway in breast cancer cells.Methods Breast cancer cells (MDA-MB-231) were treated with folate alone or in combination with a PTEN specific inhibitor, SF1670. Cell viability was detected by a MTT assay, and the expression levels of apoptosis-related proteins and PTEN/AKT/P53 signaling pathway were detected via Western blot analysis. Rate of apoptosis was measured via cytometry.Results Folic acid inhibited the cell viability of MDAMB-231 cells and the expressions of Bcl-2 and p-AKT proteins and upregulate the expression of Bax, PTEN, and P53 proteins, thereby inducing apoptosis in these cells. SF1670 treatment inhibited the expressions of Bcl-2 and p-AKT protein and upregulate Bax, PTEN, and P53 protein expression.Conclusion Folic acid has cytotoxic effects on MDAMB-231 cells and can induce apoptosis by targeting the PTEN/AKT/P53 signaling pathway.

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NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis

10.21203/rs.2.20090/v1 ◽

2020 ◽

Author(s):

Fenhong Kang ◽

Yanlong Wang ◽

Yaping Luo ◽

Yongjun Zhang

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Apoptosis ◽

Colony Formation ◽

G1 Phase ◽

Ovarian Cancer Cells ◽

Cycle Arrest

Abstract Background The cancer cell metastasis and the acquisition of chemotherapy resistance remain huge challenge for ovarian cancer treatment. Previously, N-myc downstream-regulated gene 2 (NDRG2) serves as a tumor suppressor for many cancers. Here, we attempted to investigate the specific roles of NDRG2 in ovarian cancer.Methods The expression levels of NDRG2 were detected by qRT-PCR or Immunoblotting assay. CCK-8 assay was employed to examine the cell viability of ovarian cancer cells. The colony formation ability was determined by colony formation assay. Flow cytometry analyses were performed to detect the cell apoptosis and cell cycle.Results Herein, we revealed that NDRG2 mRNA expression and protein levels were downregulated within both ovarian cancer tissues and cell lines. The overexpression of NDRG2 dramatically inhibited the cell viability and colony formation, whereas promoted the cell apoptosis and cell cycle arrest in G1 phase within ovarian cancer cells. More importantly, NDRG2 overexpression significantly enhanced the suppressive roles of cisplatin (DDP) in ovarian cancer cell viability. On the contrary, NDRG2 silence exerted opposing effects on ovarian cancer cells.Conclusions In summary, we provide a solid experimental basis demonstrating the tumor-suppressive effects of NDRG2 in inhibiting the cell proliferation, enhancing the cell apoptosis, eliciting the cell cycle arrest in G1 phase, and promoting the suppressive effects of DDP on the viability of ovarian cancer cells. NDRG2 administration presents a potent adjuvant treatment for ovarian cancer therapy, which needs further in vivo and clinical investigation.

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Poly(N-Isopropylacrylamide)-Functional Silicon Nanocrystals for Thermosensitive Fluorescence Cellar Imaging

Polymers ◽

10.3390/polym12112565 ◽

2020 ◽

Vol 12 (11) ◽

pp. 2565

Author(s):

Yiting Li ◽

Lihui Zhang ◽

Youhong Shi ◽

Jialing Huang ◽

Yaqiong Yang ◽

...

Keyword(s):

Folic Acid ◽

Cancer Cells ◽

Silicon Nanocrystals ◽

Water Solubility ◽

Fluorescence Emission ◽

Normal Pressure ◽

Polymerization Process ◽

Solution Temperature ◽

One Pot ◽

Silicon Crystals

Silicon nanocrystals (Si NCs) have received surging interest as a type of quantum dot (QD) due to the availability of silicon in nature, tunable fluorescence emission properties and excellent biocompatibility. More importantly, compared with many group II–VI and III–V based QDs, they have low toxicity. Here, thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm)-functional Si NCs were firstly prepared for thermoresponsive detection of cancer cells. Si NCs were prepared under normal pressure with excellent water solubility. Then folic acid was bonded to the silicon nanocrystals through the reaction of amino and carboxyl groups for specific recognition of cancer cells. The folic-acid-modified silicon crystals (Si NCs-FA) could be modified by a one-pot copolymerization process into PNIPAAm nanospheres during the monomer polymerization process (i.e., Si NCs-FA-PNIPAAm) just by controlling the temperature below the lower critical solution temperature (LCST) and above the LCST. The results showed that the Si-FA-PNIAAm nanospheres exhibited not only reversible temperature-responsive on-off fluorescence properties, but also can be used as temperature indicators in cancer cells.

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Rnf2 knockdown reduces cell viability and promotes cell cycle arrest in gastric cancer cells

Oncology Letters ◽

10.3892/ol.2017.5868 ◽

2017 ◽

Vol 13 (5) ◽

pp. 3817-3822 ◽

Cited By ~ 9

Author(s):

Jingfang Zhang ◽

Zhenni Sun ◽

Yafei Han ◽

Ruyong Yao ◽

Lu Yue ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Viability ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Gastric Cancer Cells ◽

Cycle Arrest

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Enhanced Photodynamic Anticancer Activities of Multifunctional Magnetic Nanoparticles (Fe3O4) Conjugated with Chlorin e6 and Folic Acid in Prostate and Breast Cancer Cells

Nanomaterials ◽

10.3390/nano8090722 ◽

2018 ◽

Vol 8 (9) ◽

pp. 722 ◽

Cited By ~ 12

Author(s):

Kyong-Hoon Choi ◽

Ki Nam ◽

Guangsup Cho ◽

Jin-Seung Jung ◽

Bong Park

Keyword(s):

Photodynamic Therapy ◽

Folic Acid ◽

Magnetic Nanoparticles ◽

Cancer Cells ◽

Biological Effects ◽

Chlorin E6 ◽

Deep Penetration ◽

Promising Alternative ◽

Long Wavelength

Photodynamic therapy (PDT) is a promising alternative to conventional cancer treatment methods. Nonetheless, improvement of in vivo light penetration and cancer cell-targeting efficiency remain major challenges in clinical photodynamic therapy. This study aimed to develop multifunctional magnetic nanoparticles conjugated with a photosensitizer (PS) and cancer-targeting molecules via a simple surface modification process for PDT. To selectively target cancer cells and PDT functionality, core magnetic (Fe3O4) nanoparticles were covalently bound with chlorin e6 (Ce6) as a PS and folic acid (FA). When irradiated with a 660-nm long-wavelength light source, the Fe3O4-Ce6-FA nanoparticles with good biocompatibility exerted marked anticancer effects via apoptosis, as confirmed by analyzing the translocation of the plasma membrane, nuclear fragmentation, activities of caspase-3/7 in prostate (PC-3) and breast (MCF-7) cancer cells. Ce6, used herein as a PS, is thus more useful for PDT because of its ability to produce a high singlet oxygen quantum yield, which is owed to deep penetration by virtue of its long-wavelength absorption band; however, further in vivo studies are required to verify its biological effects for clinical applications.

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Multifunctional phosphate based nanoparticles as a platform for imaging, targeting and doxorubicin delivery to human breast cancer CD44+ cells.

10.1101/2021.11.08.467718 ◽

2021 ◽

Author(s):

Priscila Izabel Santos de Totaro

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Cell Viability ◽

Cancer Cells ◽

Tumor Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Biological Effects ◽

Human Breast ◽

Mcf 7

Functionalized nanostructured systems can be used for imaging and drug delivery for anti-tumor therapy, including breast tumors. This is a more efficient approach that offers reduced systemic side effects compared to conventional diagnostic and chemotherapy methods. Multifunctional nanoparticles are potential tools in the diagnosis, location tracing and kill tumor cells through a less invasive manner. Functionalized phosphate-based nanoparticles are capable of encapsulating, or may be associated, with fluorescent probes. In this study, we synthesize a nanoparticle phosphate-based composite (NPC) and functionalize it with poly-ethylene glycol (PEG), hyaluronic acid (HA), the fluorescent probe rhodamin 6G (R6G) and the antimitotic doxorubicin (DOX). We focused on targeting human breast cancer cells reporting the biological effects of functionalized NPC on them. NPC and NPC formulations containing PEG, HA, and R6G did not cause cell viability reduction on MCF-7 and MDA-MB-231 cell lines. The cellular internalization of NPC was quantified by real-time in vitro observation, and confirmed by electron microscopy techniques. Intracellular NPC distribution is detected in the cytoplasm and nucleus of tumor cells by confocal fluorescent images. The percent association of doxorubicin to NPC matrix was approximately 18% and NPC formulations associated with doxorubicin led to a significant reduction in cell viability in MDA-MB-231 and MCF-7 cells. This data suggest the potential use of NPC as a non-cytotoxic platform for association with functional ligands to selective targeting breast cancer cells. NPC use can be also explored in drug delivery to cancer cells.

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