Active-passive Strategy for Enhanced Synergistic Photothermal-Ferroptosis Therapy in NIR-I/II Biowindows

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

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CD59 receptor targeted delivery of miRNA-1284 and cisplatin-loaded liposomes for effective therapeutic efficacy against cervical cancer cells

AMB Express ◽

10.1186/s13568-020-00990-z ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Li Wang ◽

Ting-Ting Liang

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Targeted Delivery ◽

Therapeutic Efficacy ◽

Cervical Cancer Cells

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Enhanced antineoplastic/therapeutic efficacy using 5-fluorouracil-loaded calcium phosphate nanoparticles

Beilstein Journal of Nanotechnology ◽

10.3762/bjnano.9.233 ◽

2018 ◽

Vol 9 ◽

pp. 2499-2515 ◽

Cited By ~ 4

Author(s):

Shanid Mohiyuddin ◽

Saba Naqvi ◽

Gopinath Packirisamy

Keyword(s):

Electron Microscopy ◽

Calcium Phosphate ◽

Cancer Cells ◽

Therapeutic Efficacy ◽

Therapeutic Potential ◽

Physicochemical Characterization ◽

A549 Cells ◽

Dependent Manner ◽

Calcium Phosphate Nanoparticles ◽

Apoptotic Induction

In the past few decades, the successful theranostic application of nanomaterials in drug delivery systems has significantly improved the antineoplastic potency of conventional anticancer therapy. Several mechanistic advantages of nanomaterials, such as enhanced permeability, retention, and low toxicity, as well as surface engineering with targeting moieties, can be used as a tool in enhancing the therapeutic efficacy of current approaches. Inorganic calcium phosphate nanoparticles have the potential to increase the therapeutic potential of antiproliferative drugs due to their excellent loading efficiency, biodegradable nature and controlled-release behaviour. Herein, we report a novel system of 5-fluorouracil (5-FU)-loaded calcium phosphate nanoparticles (CaP@5-FU NPs) synthesized via a reverse micelle method. The formation of monodispersed, spherical, crystalline nanoparticles with an approximate diameter of 160–180 nm was confirmed by different methods. The physicochemical characterization of the synthesized CaP@5-FU NPs was done with transmission electron microscopy (TEM), dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The antineoplastic potential of the CaP@5-FU NPs against colorectal and lung cancer cells was reported. The CaP@5-FU NPs were found to inhibit half the population (IC50) of lung adenocarcinoma (A549) cells at 32 μg/mL and colorectal (HCT-15) cancer cells at 48.5 μg/mL treatment. The apoptotic induction of CaP@5-FU NPs was confirmed with acridine orange/ethidium bromide (AO/EB) staining and by examining the morphological changes with Hoechst and rhodamine B staining in a time-dependent manner. The apparent membrane bleb formation was observed in FE-SEM micrographs. The up-regulated proapoptotic and down-regulated antiapoptotic gene expressions were further confirmed with semiquantitative reverse transcriptase polymerase chain reaction (PCR). The increased intracellular reactive oxygen species (ROS) were quantified via flow cytometry upon CaP@5-FU NP treatment. Likewise, the cell cycle analysis was performed to confirm the enhanced apoptotic induction. Our study concludes that the calcium phosphate nanocarriers system, i.e. CaP@5-FU NPs, has higher antineoplastic potential as compared to 5-FU alone and can be used as an improved alternative to the antimitotic drug, which causes severe side effects when administrated alone.

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Therapeutic Efficacy of Genistein-Topotecan Combination Compared to Vitamin D3-Topotecan Combination in LNCaP Prostate Cancer Cells

CellBio ◽

10.4236/cellbio.2013.23011 ◽

2013 ◽

Vol 02 (03) ◽

pp. 97-104

Author(s):

Shreyasee Chakraborty ◽

Bibiana Sandoval-Bernal ◽

James Kumi-Diaka

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Vitamin D3 ◽

Therapeutic Efficacy ◽

Prostate Cancer Cells

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DGAT1 is a lipid metabolism oncoprotein that enables cancer cells to accumulate fatty acid while avoiding lipotoxicity

10.1101/2020.06.23.166603 ◽

2020 ◽

Cited By ~ 1

Author(s):

Daniel J. Wilcock ◽

Andrew P. Badrock ◽

Rhys Owen ◽

Melissa Guerin ◽

Andrew D. Southam ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Cell Growth ◽

Cancer Cells ◽

Melanoma Cell ◽

Drug Targets ◽

Lipid Peroxides ◽

Acid Oxidation ◽

Growth Factor Signaling ◽

Bona Fide

ABSTRACTDysregulated cellular metabolism is a hallmark of cancer. As yet, few druggable oncoproteins directly responsible for this hallmark have been identified. Increased fatty acid acquisition allows cancer cells to meet their membrane biogenesis, ATP, and signaling needs. Excess fatty acids suppress growth factor signaling and cause oxidative stress in non-transformed cells, but surprisingly not in cancer cells. Molecules underlying this cancer adaptation may provide new drug targets. Here, we identify Diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, as a frequently up-regulated oncoprotein allowing cancer cells to tolerate excess fatty acids. DGAT1 over-expression alone induced melanoma in zebrafish melanocytes, and co-operated with oncogenic BRAF or NRAS for more rapid melanoma formation. Mechanistically, DGAT1 stimulated melanoma cell growth through sustaining mTOR kinase–S6 kinase signaling and suppressed cell death by tempering fatty acid oxidation, thereby preventing accumulation of reactive oxygen species including lipid peroxides.SIGNIFICANCEWe show that DGAT1 is a bona fide oncoprotein capable of inducing melanoma formation and co-operating with other known drivers of melanoma. DGAT1 facilitates enhanced fatty acid acquisition by melanoma cells through suppressing lipototoxicity. DGAT1 is also critical for maintaining S6K activity required for melanoma cell growth.

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Abstract 367: Assessing the therapeutic efficacy of Cyst(e)inase to induce oxidative stress mediated cytotoxicity in pancreatic cancer cells

10.1158/1538-7445.am2016-367 ◽

2016 ◽

Author(s):

Sabin Kshattry ◽

Achinto Saha ◽

Shira Cramer ◽

Everett M. Stone ◽

George Georgiou ◽

...

Keyword(s):

Oxidative Stress ◽

Pancreatic Cancer ◽

Cancer Cells ◽

Therapeutic Efficacy ◽

Pancreatic Cancer Cells

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205 SELECTIVE ANTITUMOR THERAPEUTIC EFFECT OF 5-FLUOROCYTOSINE AND INTERFERON-BETA AGAINST BREAST AND ENDOMETRIAL CANCER CELLS BY ENGINEERED STEM CELLS EXPRESSING CYTOSINE DEAMINASE AND HUMAN INTERFERON-BETA

Reproduction Fertility and Development ◽

10.1071/rdv24n1ab205 ◽

2012 ◽

Vol 24 (1) ◽

pp. 215

Author(s):

B.-R. Yi ◽

K.-A. Hwang ◽

K.-C. Choi

Keyword(s):

Stem Cells ◽

Endometrial Cancer ◽

Stem Cell ◽

Cell Viability ◽

Cancer Cells ◽

Therapeutic Efficacy ◽

Interferon Beta ◽

Cytosine Deaminase ◽

Genetically Engineered ◽

Human Interferon

When genetically engineered with chemo- or immunotherapeutic genes, stem cells can exhibit a potent therapeutic efficacy combined with their strong tumour tropism. The stem cells were genetically engineered to express a bacterial cytosine deaminase (CD) gene and/or a human interferon-β (IFN-b) gene; thus, 2 stem cell lines, HB1.F3.CD and HB1.F3.CD.IFN-b, were generated, respectively. The CD gene, one of suicide gene, can convert the nontoxic prodrug 5-fluorocytosine (5-FC) to an active form, 5-fluorouracil (5-FU), which has a powerful cytotoxic effect on cancer cells. In addition, human IFN-b is a typical cytokine having an antitumour effect. Using reverse transcription-PCR (RT-PCR), we confirmed CD and/or IFN-b gene expression in HB1.F3 (maternal stem cells) and HB1.F3.CD and HB1.F3.CD.IFN-b cells and the expression of chemoattractant ligands and receptors including stem cell factor (SCF), CXCR4, c-kit, vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in breast (MCF-7) and endometrial cancer (Ishikawa) cells. To determine the migratory capability of engineered stem cells, we performed a modified trans-well assay. In addition, to identify their therapeutic efficacy, we co-cultured HB1.F3.CD or HB1.F3.CD.IFN-b with breast and endometrial cancer cells and cell viability was measured by MTT assay. The engineered stem cells expressed CD and IFN-b genes and several chemoattractant molecules, SCF, CXCR4, VEGF/VEGFR2 and c-kit, were strongly expressed in breast and endometrial cancer cells. These stem cells were effectively migrated to breast and endometrial cancer cells due to chemoattractant molecules secreted by breast and endometrial cancer cells. In therapeutic efficacy, the viability of breast and endometrial cancer cells treated with 5-FC was reduced in the presence of the HB1.F3.CD and HB1.F3.CD.IFN-b cells. Cell viability was more reduced when co-cultured with HB1.F3.CD.IFN-b compared with HB1.F3.CD cells. In conclusion, the results from the present study suggest that genetically modified stem cells expressing CD and IFN-b can be used as a gene-based therapy for treating breast and endometrial cancer via their tumour tropism. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0005723).

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