Nucleoside Transporter-guided Cytarabine Conjugated Liposomes for Intracellular Methotrexate Delivery and Cooperative Choriocarcinoma Therapy

2021 ◽  
Author(s):  
Weidong Fei ◽  
Yunchun Zhao ◽  
Xiaodong Wu ◽  
Dongli Sun ◽  
Yao Yao ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Rational Design ◽  
High Efficiency ◽  
Nucleoside Transporter ◽  
Childbearing Age ◽  
Equilibrative Nucleoside Transporter ◽  
Choriocarcinoma Cells ◽  
Tumor Accumulation ◽  
Novel Strategy ◽  
Distribution Studies

Abstract The gestational trophoblastic tumor seriously endangers child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides novel strategy for the treatment of trophoblastic tumors. Focus on the overexpressed human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), the cytarabine (Cy, a substrate of ENT1) grafted liposome (Cy-Lipo) was introduced for targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. The ENT1 has high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transporting function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations achieved high tumor accumulation and retention in pharmacokinetic and distribution studies. More importantly, the designed Cy-lipid conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, Cy-Lipo@MTX exerts an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds a great potential to be a high-efficiency target for the rational design of active targeting nanotherapeutics.

scholarly journals Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weidong Fei ◽  
Yunchun Zhao ◽  
Xiaodong Wu ◽  
Dongli Sun ◽  
Yao Yao ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Rational Design ◽  
High Efficiency ◽  
Nucleoside Transporter ◽  
Childbearing Age ◽  
Biodistribution Studies ◽  
Trophoblastic Tumors ◽  
Choriocarcinoma Cells ◽  
Tumor Accumulation ◽  
Novel Strategy

AbstractGestational trophoblastic tumors seriously endanger child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides a novel strategy for the treatment of trophoblastic tumors. Focusing on the overexpression of human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), cytarabine (Cy, a substrate of ENT1)-grafted liposomes (Cy-Lipo) were introduced for the targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. ENT1 has a high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transportation function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations showed high tumor accumulation and retention in biodistribution studies. More importantly, the designed DSPE-PEG2k-Cy conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, Cy-Lipo@MTX exerted an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds great potential as a high-efficiency target for the rational design of active targeting nanotherapeutics. Graphic abstract

scholarly journals Novel Strategy with Gemcitabine for Advanced Pancreatic Cancer

ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Shuji Komori ◽  
Shinji Osada ◽  
Kazuhiro Yoshida
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Metabolic Enzymes ◽  
Interindividual Variation ◽  
Nucleoside Transporter ◽  
Standard Drug ◽  
Equilibrative Nucleoside Transporter ◽  
Nucleotide Pools ◽  
Novel Strategy

5-fluorouracil (5-FU) is widely used in chemotherapy for gastric and colorectal cancer, but gemcitabine (GEM), and not 5-FU, is approved as a standard drug for use in pancreatic cancer. Interindividual variation in the enzyme activity of the GEM metabolic pathway can affect the extent of GEM metabolism and the efficacy of GEM chemotherapy. Human equilibrative nucleoside transporter 1 (hENT1) is recognized as a major transporter of GEM into cells. In addition, a factor that activates hENT1 is the inhibition of thymidylate synthase (TS), one of the 5-FU metabolic enzymes; TS inhibition mediates depleting intracellular nucleotide pools, resulting in the activation of the salvage pathway mediated through hENT1. In this paper, the role of 5-FU in GEM-based chemotherapy for pancreatic cancer is discussed with special emphasis on enzymes involved in the 5-FU and GEM metabolic pathways and in the correlation between GEM responsiveness and the expression of 5-FU and GEM metabolic enzymes.

scholarly journals Equilibrative nucleoside transporter 1 inhibition rescues energy dysfunction and pathology in a model of tauopathy

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Ching-Pang Chang ◽  
Ya-Gin Chang ◽  
Pei-Yun Chuang ◽  
Thi Ngoc Anh Nguyen ◽  
Kuo-Chen Wu ◽  
...  
Keyword(s):  
Nucleoside Transporter ◽  
Tau Pathology ◽  
Synaptic Loss ◽  
Equilibrative Nucleoside Transporter ◽  
Beneficial Effects ◽  
Molecular Alterations ◽  
Gradual Loss ◽  
Novel Strategy ◽  
Neuronal Functions ◽  
The Brain

AbstractTau pathology is instrumental in the gradual loss of neuronal functions and cognitive decline in tauopathies, including Alzheimer’s disease (AD). Earlier reports showed that adenosine metabolism is abnormal in the brain of AD patients while consequences remained ill-defined. Herein, we aimed at investigating whether manipulation of adenosine tone would impact Tau pathology, associated molecular alterations and subsequent neurodegeneration. We demonstrated that treatment with an inhibitor (J4) of equilibrative nucleoside transporter 1 (ENT1) exerted beneficial effects in a mouse model of Tauopathy. Treatment with J4 not only reduced Tau hyperphosphorylation but also rescued memory deficits, mitochondrial dysfunction, synaptic loss, and abnormal expression of immune-related gene signatures. These beneficial effects were particularly ascribed to the ability of J4 to suppress the overactivation of AMPK (an energy reduction sensor), suggesting that normalization of energy dysfunction mitigates neuronal dysfunctions in Tauopathy. Collectively, these data highlight that targeting adenosine metabolism is a novel strategy for tauopathies.

Nano Technological Approach for Anti-Tumor Therapy: Opportunities and Challenges

2020 ◽  
Vol 10 ◽  
Author(s):  
Krishna Champaneria ◽  
Prajesh Prajapati
Keyword(s):  
Adverse Effects ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Blood Circulation ◽  
Review Paper ◽  
Tumor Therapy ◽  
Conventional Chemotherapy ◽  
Targeting Delivery ◽  
Tumor Accumulation ◽  
Work Done

Cancer is one of the reason for mortality and its individual and collective impact is substantial. Conventional chemotherapy utilizes drugs that can destroy Tumor cells effectively. But these agents destroy healthy cells along with the tumor cells, leading to many adverse effects which include hypersensitivity reactions, nephrotoxicity, and neurotoxicity. To minimize the adverse effects, various drug delivery systems (DDSs) has been developed. Among them, nanoparticles are attractive platforms for it. So this review paper explores the recent work done on targeted delivery, enhancing tumor accumulation and longer blood circulation using more effective biomaterial that will enhance the properties of nanoparticles. Moreover, various target-specific delivery of drugs like antibody-targeted, targeting delivery through angiogenesis, mitochondria, CD44 receptor are also explained.

scholarly journals Improving the Utility of a Dynorphin Peptide Analogue Using Mannosylated Glycoliposomes

2021 ◽  
Vol 22 (15) ◽  
pp. 7996
Author(s):  
Jordan D. Lewicky ◽  
Nya L. Fraleigh ◽  
Alexandrine L. Martel ◽  
Thi M.-D. Nguyen ◽  
Peter W. Schiller ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Delivery Systems ◽  
Kappa Opioid Receptor ◽  
Antagonist Activity ◽  
Peptide Analogue ◽  
Nanoparticle Delivery ◽  
The Central Nervous System ◽  
Metabolic Degradation ◽  
Distribution Studies

Peptide therapeutics offer numerous advantages in the treatment of diseases and disorders of the central nervous system (CNS). However, they are not without limitations, especially in terms of their pharmacokinetics where their metabolic lability and low blood–brain barrier penetration hinder their application. Targeted nanoparticle delivery systems are being tapped for their ability to improve the delivery of therapeutics into the brain non-invasively. We have developed a family of mannosylated glycoliposome delivery systems for targeted drug delivery applications. Herein, we demonstrate via in vivo distribution studies the potential of these glycoliposomes to improve the utility of CNS active therapeutics using dynantin, a potent and selective dynorphin peptide analogue antagonist of the kappa opioid receptor (KOR). Glycoliposomal entrapment protected dynantin against known rapid metabolic degradation and ultimately improved brain levels of the peptide by approximately 3–3.5-fold. Moreover, we linked this improved brain delivery with improved KOR antagonist activity by way of an approximately 30–40% positive modulation of striatal dopamine levels 20 min after intranasal administration. Overall, the results clearly highlight the potential of our glycoliposomes as a targeted delivery system for therapeutic agents of the CNS.

scholarly journals Biomarkers in Pancreatic Cancer as Analytic Targets for Nanomediated Imaging and Therapy

Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 3083
Author(s):  
Cristiana Maria Grapa ◽  
Lucian Mocan ◽  
Dana Crisan ◽  
Mira Florea ◽  
Teodora Mocan
Keyword(s):  
Drug Delivery ◽  
Pancreatic Cancer ◽  
Targeted Delivery ◽  
Drug Toxicity ◽  
Treatment Options ◽  
Tumor Stroma ◽  
Chemotherapy Response ◽  
Rising Incidence ◽  
Tumor Accumulation ◽  
Accumulation Ability

As the increase in therapeutic and imaging technologies is swiftly improving survival chances for cancer patients, pancreatic cancer (PC) still has a grim prognosis and a rising incidence. Practically everything distinguishing for this type of malignancy makes it challenging to treat: no approved method for early detection, extended asymptomatic state, limited treatment options, poor chemotherapy response and dense tumor stroma that impedes drug delivery. We provide a narrative review of our main findings in the field of nanoparticle directed treatment for PC, with a focus on biomarker targeted delivery. By reducing drug toxicity, increasing their tumor accumulation, ability to modulate tumor microenvironment and even improve imaging contrast, it seems that nanotechnology may one day give hope for better outcome in pancreatic cancer. Further conjugating nanoparticles with biomarkers that are overexpressed amplifies the benefits mentioned, with potential increase in survival and treatment response.

Contribution of equilibrative nucleoside transporter (ENT) 2 to fluorouracil transport in rat placental trophoblast cells

2017 ◽  
Vol 32 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Akinori Takagi ◽  
Tomohiro Nishimura ◽  
Tomoya Akashi ◽  
Masatoshi Tomi ◽  
Emi Nakashima
Keyword(s):  
Nucleoside Transporter ◽  
Trophoblast Cells ◽  
Equilibrative Nucleoside Transporter
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