scholarly journals Evaluation of Riboflavin Transporters as Targets for Drug Delivery and Theranostics

2019 ◽  
Vol 10 ◽  
Author(s):  
Lisa Bartmann ◽  
David Schumacher ◽  
Saskia von Stillfried ◽  
Marieke Sternkopf ◽  
Setareh Alampour-Rajabi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Constitutive Expression ◽  
Tumor Stroma ◽  
Cellular Growth ◽  
Kidney Cells ◽  
Luminal A ◽  
Uptake Mechanism

The retention and cellular internalization of drug delivery systems and theranostics for cancer therapy can be improved by targeting molecules. Since an increased uptake of riboflavin was reported for various cancers, riboflavin and its derivatives may be promising binding moieties to trigger internalization via the riboflavin transporters (RFVT) 1, 2, and 3. Riboflavin is a vitamin with pivotal role in energy metabolism and indispensable for cellular growth. In previous preclinical studies on mice, we showed the target-specific accumulation of riboflavin-functionalized nanocarriers in cancer cells. Although the uptake mechanism of riboflavin has been studied for over a decade, little is known about the riboflavin transporters and their expression on cancer cells, tumor stroma, and healthy tissues. Furthermore, evidence is lacking concerning the representativeness of the preclinical findings to the situation in humans. In this study, we investigated the expression pattern of riboflavin transporters in human squamous cell carcinoma (SCC), melanoma and luminal A breast cancer samples, as well as in healthy skin, breast, aorta, and kidney tissues. Low constitutive expression levels of RFVT1–3 were found on all healthy tissues, while RFVT2 and 3 were significantly overexpressed in melanoma, RFVT1 and 3 in luminal A breast cancer and RFVT1–3 in SCC. Correspondingly, the SCC cell line A431 was highly positive for all RFVTs, thus qualifying as suitable in vitro model. In contrast, activated endothelial cells (HUVEC) only presented with a strong expression of RFVT2, and HK2 kidney cells only with a low constitutive expression of RFVT1–3. Functional in vitro studies on A431 and HK2 cells using confocal microscopy showed that riboflavin uptake is mostly ATP dependent and primarily driven by endocytosis. Furthermore, riboflavin is partially trafficked to the mitochondria. Riboflavin uptake and trafficking was significantly higher in A431 than in healthy kidney cells. Thus, this manuscript supports the hypothesis that addressing the riboflavin internalization pathway may be highly valuable for tumor targeted drug delivery.

Polymer Coated Iron Nanoparticles: Radiolabeling & In Vitro Studies

2020 ◽  
Vol 13 ◽  
Author(s):  
Selin Yılmaz ◽  
Çiğdem İçhedef ◽  
Kadriye Buşra Karatay ◽  
Serap Teksöz
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Iron Oxide ◽  
Cancer Cells ◽  
Iron Oxide Nanoparticles ◽  
Breast Cancer Cells ◽  
Cancer Drug ◽  
Oxide Nanoparticles ◽  
Sem Images

Backgorund: Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used for targeted drug delivery systems due to their unique magnetic properties. Objective: In this study, it’s aimed to develop a novel targeted 99mTc radiolabeled polymeric drug delivery system for Gemcitabine (GEM). Methods: Gemcitabine, an anticancer agent, was encapsulated into polymer nanoparticles (PLGA) together with iron oxide nanoparticles via double emulsion technique and then labeled with 99mTc. SPIONs were synthesized by reduction–coprecipitation method and encapsulated with oleic acid for surface modification. Size distribution and the morphology of the synthesized nanoparticles were caharacterized by dynamic light scattering(DLS)and scanning electron microscopy(SEM), respectively. Radiolabeling yield of SPION-PLGAGEM nanoparticles were determined via Thin Layer Radio Chromatography (TLRC). Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells in vitro. Results: SEM images displayed that the average size of the drug-free nanoparticles was 40 nm and the size of the drug-loaded nanoparticles was 50 nm. The diameter of nanoparticles were determined as 366.6 nm by DLS, while zeta potential was found as-29 mV. SPION was successfully coated with PLGA, which was confirmed by FTIR. GEM encapsulation efficiency of SPION-PLGA was calculated as 4±0.16 % by means of HPLC. Radiolabeling yield of SPION-PLGA-GEM nanoparticles were determined as 97.8±1.75 % via TLRC. Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells. SPION-PLGA-GEM showed high uptake on MCF-7, whilst incorporation rate was increased for both cell lines which external magnetic field application. Conclusion: 99mTc labeled SPION-PLGA nanoparticles loaded with GEM may overcome some of the obstacles in anti-cancer drug delivery because of their appropriate size, non-toxic, and supermagnetic characteristics.

scholarly journals Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Click Reaction ◽  
Chemotherapy Drugs ◽  
Targeting Peptide ◽  
And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

Folic acid-functionalized niosomal nanoparticles for selective dual-drug delivery into breast cancer cells: An in-vitro investigation

2020 ◽  
Vol 31 (9) ◽  
pp. 4064-4071
Author(s):  
Iman Akbarzadeh ◽  
Mohammad Tavakkoli Yaraki ◽  
Saeedeh Ahmadi ◽  
Mohsen Chiani ◽  
Dariush Nourouzian
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Folic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vitro Investigation ◽  
Dual Drug

scholarly journals Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Chandran Murugan ◽  
Kathirvel Rayappan ◽  
Ramar Thangam ◽  
Ramasamy Bhanumathi ◽  
Krishnamurthy Shanthi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Structural Changes ◽  
Silica Nanoparticle ◽  
Therapeutic Effects ◽  
Multiple Drugs

Abstract Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms as in vitro and in vivo. The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT. Subsequently, grafting of arginine-glycine-aspartic acid (cRGD) peptide on the surface of nanocarrier (CPMSN) thwarted the uptake by normal cells, but facilitated their uptake in cancer cells through integrin receptor mediated endocytosis and the dissociation of nanocarriers due to the ability to degrade CS and PAA in acidic pH, which enhance the intracellular release of drugs. Subsequently, the released drugs induce remarkable molecular activation as well as structural changes in tumor cell endoplasmic reticulum, nucleus and mitochondria that can trigger cell death. The valuable CPMSNs may open up new avenues in developing targeted therapeutic strategies to treat cancer through serving as an effective drug delivery podium.

scholarly journals Encapsulation of Quercetin in Tri-Block-Copolymer/Tween 80 Mixed Nanomicelles to Enhance its Cytotoxicity Against Breast Cancer Cells

2021 ◽  
Author(s):  
Reza Davarnejad ◽  
Kiyana Layeghy ◽  
Meysam Soleymani ◽  
Arvin Ayazi
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Drug Delivery System ◽  
Delivery System ◽  
Breast Cancer Cells ◽  
Therapeutic Potential ◽  
Tween 80 ◽  
Prolonged Release

Abstract Quercetin, a natural polyphenolic compound, has attracted much attention due to its great therapeutic potential against various types of diseases. But clinical applications of quercetin are limited due to its poor aqueous solubility and low bioavailability. The main purpose of this research was to evaluate the therapeutic potential of quercetin-loaded Pluronic F127 (PF127)/Tween 80 mixed nanomicelles as a passive targeted drug delivery system for breast cancer therapy. To this end, quercetin-loaded mixed nanomicelles with different mass ratios of drug:PF127:Tween 80 were prepared by the thin-film hydration method. The highest drug loading and entrapment efficiency were obtained to be 2.3% and 98.0%, respectively, for mixed micelles with drug:PF127:Tween 80 ratio of 1:40:15. The physical interactions of quercetin with PF127 and Tween 80 at optimized ratio was investigated by XRD and FTIR analyses. The mean hydrodynamic size and surface charge of prepared nanomicelles, measured by DLS and zeta potential analyses, were 22.1 nm and -7.63 mV, respectively. The results of in-vitro drug release experiments showed that, the mixed micellar system has a prolong and sustained release behavior compared to the solution of free quercetin. Moreover, the in-vitro cytotoxicity studies of quercetin-loaded mixed nanomicelles on breast cancer cells (MCF-7) revealed that, the encapsulated drug have a lower IC50 value (8.9 µg/mL) compared to the free drug (49.2 µg/mL). Our results suggest that, quercetin-loaded mixed nanomicelles can be considered as a promising drug delivery system with prolonged release and potentiated cytotoxicity against breast cancer cells.

Hydrophobic myristic acid modified PAMAM dendrimers augment the delivery of tamoxifen to breast cancer cells

RSC Advances ◽  
2016 ◽  
Vol 6 (30) ◽  
pp. 24808-24819 ◽  
Author(s):  
Ishita Matai ◽  
P. Gopinath
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Myristic Acid ◽  
Breast Cancer Cells ◽  
Pamam Dendrimers ◽  
Hydrophobically Modified ◽  
Delivery Vector

In the present study, cationic generation 5 polyamido amine (G5 PAMAM) dendrimers were hydrophobically modified by grafting the surface with lipid-like myristic acid (My) tails to augment their potential as a drug delivery vector in vitro.

scholarly journals Combined p53- and PTEN-deficiency activates expression of mesenchyme homeobox 1 (MEOX1) required for growth of triple-negative breast cancer

2020 ◽  
Vol 295 (34) ◽  
pp. 12188-12202
Author(s):  
Mari Gasparyan ◽  
Miao-Chia Lo ◽  
Hui Jiang ◽  
Chang-Ching Lin ◽  
Duxin Sun
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Normal Breast ◽  
Luminal A ◽  
Tyrosine Kinase 2 ◽  
Breast Cells

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype for which effective therapies are unavailable. TNBC has a high frequency of tumor protein p53 (Tp53/p53)- and phosphatase and tensin homolog (PTEN) deficiencies, and combined p53- and PTEN-deficiency is associated with poor prognosis and poor response to anticancer therapies. In this study, we discovered that combined p53- and PTEN-deficiency in TNBC activates expression of the transcription factor mesenchyme homeobox 1 (MEOX1). We found that MEOX1 is expressed only in TNBC cells with frequent deficiencies in p53 and PTEN, and that its expression is undetectable in luminal A, luminal B, and HER2+ subtypes, as well as in normal breast cells with wild-type (WT) p53 and PTEN. Notably, siRNA knockdown of both p53 and PTEN activated MEOX1 expression in breast cancer cells, whereas individual knockdowns of either p53 or PTEN had only minimal effects on MEOX1 expression. MEOX1 knockdown abolished cell proliferation of p53- and PTEN-deficient TNBC in vitro and inhibited tumor growth in vivo, but had no effect on the proliferation of luminal and HER2+ cancer cells and normal breast cells. RNA-Seq and immunoblotting analyses showed that MEOX1 knockdown decreased expression of tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 5B (STAT5B), and STAT6 in p53- and PTEN-deficient TNBC cells. These results reveal the effects of combined p53- and PTEN-deficiency on MEOX1 expression and TNBC cell proliferation, suggesting that MEOX1 may serve as a potential therapeutic target for managing p53- and PTEN-deficient TNBC.

scholarly journals Furin Prodomain ppFurin Enhances Ca2+ Entry Through Orai and TRPC6 Channels’ Activation in Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1670
Author(s):  
Jose J. López ◽  
Geraldine Siegfried ◽  
Carlos Cantonero ◽  
Fabienne Soulet ◽  
Jean Descarpentrie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vitro Digestion ◽  
Cellular Growth ◽  
Malignant Phenotype ◽  
Factor C ◽  
Orai Channels

The intracellular calcium concentration ([Ca2+]i) modulation plays a key role in the regulation of cellular growth and survival in normal cells and failure of [Ca2+]i homeostasis is involved in tumor initiation and progression. Here we showed that inhibition of Furin by its naturally occurring inhibitor the prodomain ppFurin in the MDA-MB-231 breast cancer cells resulted in enhanced store-operated calcium entry (SOCE) and reduced the cell malignant phenotype. Expression of ppFurin in a stable manner in MDA-MB-231 and the melanoma MDA-MB-435 cell lines inhibits Furin activity as assessed by in vitro digestion assays. Accordingly, cell transfection experiments revealed that the ppFurin-expressing cells are unable to adequately process the proprotein convertase (PC) substrates vascular endothelial growth factor C (proVEGF-C) and insulin-like growth factor-1 receptor (proIGF-1R). Compared to MDA-MB-435 cells, expression of ppFurin in MDA-MB-231 and BT20 cells significantly enhanced SOCE and induced constitutive Ca2+ entry. The enhanced SOCE is impaired by inhibition of Orai channels while the constitutive Ca2+ entry is attenuated by silencing or inhibition of TRPC6 or inhibition of Orai channels. Analysis of TRPC6 activation revealed its upregulated tyrosine phosphorylation in ppFurin-expressing MDA-MB-231 cells. In addition, while ppFurin had no effect on MDA-MB-435 cell viability, in MDA-MB-231 cells ppFurin expression reduced their viability and ability to migrate and enhanced their sensitization to the apoptosis inducer hydrogen peroxide and similar results were observed in BT20 cells. These findings suggest that Furin inhibition by ppFurin may be a useful strategy to interfere with Ca2+ mobilization, leading to breast cancer cells’ malignant phenotype repression and reduction of their resistance to treatments.

scholarly journals A REVIEW ON FAST DISSOLVING TABLETIn-vitro drug release study: preparation and evaluation of chitosan anchored nanoparticles

2019 ◽  
Vol 9 (1) ◽  
pp. 6-8
Author(s):  
Rajkumari Thagele
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Release ◽  
Cancer Cells ◽  
Sodium Tripolyphosphate ◽  
Chitosan Nanoparticles ◽  
Human Beings ◽  
Drug Release Study ◽  
Release Study

Cancer has become a solemn threat to the life of human beings universally. Various strategies are available to steadfastness cancer; however they are not so effective owed to their serious side effects, noxious effect to healthy cells and non- specificity to cancer cells targeting. To tenacity above facts we try to deed inherent characters of cancer cells. HA was used as a targeting agent for drug delivery to breast cancer cells. In this work nanoparticles were equipped using chitosan and sodium tripolyphosphate encapsulating methotrexate. Methotrexate (Mtx) a folic acid antagonist that inhibits dihydrofolatereductase (DHFR) and blocks conversion of dihydrofolic acid (DHFA) to tetrahydrofolic acid (THFA) of the cell cycle. Chitosan anchored nanoparticles were prepared by ionotropic gelation method by means of sodium tripolyphosphate and evalauted for in-vitro drug release study with dialysis membrane. Result depicts that drug releases from chitosan nanoparticles in sustained manner over a prolonged episode of time from the NPs as the medium acidity enhanced at the target site, not in plasma. In conclusion, chitosan anchored nanoparticles of MTX could be well thought-out as probable candidate for drug delivery in the treatment of breast cancer. Keywords: Breast cancer, Methotrexate, Chitosan, TPP and Nanoparticles.

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