scholarly journals Impact of Polyallylamine Hydrochloride on Gene Expression and Karyotypic Stability of Multidrug Resistant Transformed Cells

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2332
Author(s):  
Larisa Alekseenko ◽  
Mariia Shilina ◽  
Irina Kozhukharova ◽  
Olga Lyublinskaya ◽  
Irina Fridlyanskaya ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Sublethal Effects ◽  
Chinese Hamster ◽  
Multidrug Resistant ◽  
Genetic Characteristics ◽  
Oncogenic Potential ◽  
Intracellular Drug Delivery ◽  
Immortalized Cells ◽  
Polyallylamine Hydrochloride ◽  
Increased Sensitivity

The synthetic polymer, polyallylamine hydrochloride (PAA), is found in a variety of applications in biotechnology and medicine. It is used in gene and siRNA transfer, to form microcapsules for targeted drug delivery to damaged and tumor cells. Conventional chemotherapy often does not kill all cancer cells and leads to multidrug resistance (MDR). Until recently, studies of the effects of PAA on cells have mainly focused on their morphological and genetic characteristics immediately or several hours after exposure to the polymer. The properties of the cell progeny which survived the sublethal effects of PAA and resumed their proliferation, were not monitored. The present study demonstrated that treatment of immortalized Chinese hamster cells CHLV-79 RJK sensitive (RJK) and resistant (RJKEB) to ethidium bromide (EB) with cytotoxic doses of PAA, selected cells with increased karyotypic instability, were accompanied by changes in the expression of p53 genes c-fos, topo2-α, hsp90, hsc70. These changes did not contribute to the progression of MDR, accompanied by the increased sensitivity of these cells to the toxic effects of doxorubicin (DOX). Our results showed that PAA does not increase the oncogenic potential of immortalized cells and confirmed that it can be used for intracellular drug delivery for anticancer therapy.

Freezing-Assisted Intracellular Drug Delivery to Multidrug Resistant Cancer Cells

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Ka Yaw Teo ◽  
Bumsoo Han
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Plasma Membranes ◽  
Cancer Cell Line ◽  
Multidrug Resistant ◽  
Drug Uptake ◽  
Freezing And Thawing ◽  
Intracellular Space ◽  
Intracellular Drug Delivery ◽  
Model Drug

The efficacy of chemotherapy is significantly impaired by the multidrug resistance (MDR) of cancer cells. The mechanism of MDR is associated with the overexpression of certain adenosine triphosphate-binding cassette protein transporters in plasma membranes, which actively pump out cytotoxic drugs from the intracellular space. In this study, we tested a hypothesis that freezing and thawing (F/T) may enhance intracellular drug delivery to MDR cancer cells via F/T-induced denaturation of MDR-associated proteins and/or membrane permeabilization. After a human MDR cancer cell line (NCI/ADR-RES) was exposed to several F/T conditions, its cellular drug uptake was quantified by a fluorescent calcein assay using calcein as a model drug. After F/T to −20°C, the intracellular uptake of calcein increased by 70.1% (n=5, P=0.0004). It further increased to 118% as NCI/ADR-RES cells were frozen/thawed to −40°C (n=3, P=0.009). These results support the hypothesis, and possible mechanisms of F/T-enhanced intracellular drug delivery were proposed and discussed.

Doxorubicin Loaded Nanoparticle Consisting of Chitosan and Mannose Modified Graphene Oxide for Intracellular Drug Delivery and Anti-tumor Activity

2020 ◽  
Vol 13 (5) ◽  
pp. 5155-5164
Author(s):  
Meena K. S. ◽  
Sonia K ◽  
Alamelu Bai S
Keyword(s):  
Drug Delivery ◽  
Graphene Oxide ◽  
Drug Delivery System ◽  
Delivery System ◽  
In Vitro Release ◽  
Cancer Drug ◽  
Hemolysis Assay ◽  
Functionalized Graphene Oxide ◽  
Intracellular Drug Delivery ◽  
Modified Graphene Oxide

In order to develop the efficiency and the specificity of anticancer drug delivery, we have designed an innovative nanocarrier. The nanocarrier system comprises of a multifunctional graphene oxide nanoparticle-based drug delivery system (GO-CS-M-DOX) as a novel platform for intracellular drug delivery of doxorubicin (DOX). Firstly, graphene oxide (GO) was synthesized by hummer’s method whose surface was functionalized by chitosan (CS) in order to obtain a more precise drug delivery, the system was then decorated with mannose (M). Further conjugation of an anti-cancer drug doxorubicin to the nanocarrier system resulted in GO-CS-M-DOX drug delivery system. The resultant conjugate was characterized for its physio-chemical properties and its biocompatibility was evaluated via hemolysis assay. The drug entrapment efficiency is as high as 90% and in vitro release studies of DOX under pH 5.3 is significantly higher than that under pH 7.4. The anticancer activity of the synthesized drug delivery system was studied by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay against MCF-7 cell line. These results stated that the pH dependent multifunctional doxorubicin- chitosan functionalized graphene oxide based nanocarrier system, could lead to a promising and potential platform for intracellular delivery and cytotoxicity activity for variety of anticancer drugs.   

scholarly journals Full length and alternatively spliced pgp1 transcripts in multidrug-resistant Chinese hamster lung cells

1991 ◽  
Vol 266 (7) ◽  
pp. 4545-4555
Author(s):  
S E Devine ◽  
A Hussain ◽  
J P Davide ◽  
P W Melera
Keyword(s):  
Chinese Hamster ◽  
Multidrug Resistant ◽  
Full Length ◽  
Lung Cells ◽  
Alternatively Spliced

scholarly journals Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 927
Author(s):  
Sebas D. Pronk ◽  
Erik Schooten ◽  
Jurgen Heinen ◽  
Esra Helfrich ◽  
Sabrina Oliveira ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Single Domain ◽  
Drug Conjugates ◽  
Intracellular Drug Delivery ◽  
Internalization Rate ◽  
Single Domain Antibodies ◽  
Different Characteristics

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to their internalization speed. The efficacy of the conjugates was inhibited in the presence of vacuolin-1, an inhibitor of lysosomal maturation, suggesting lysosomal trafficking is needed for efficient drug release. In conclusion, sdAb constructs with different internalization rates can be designed against the same target, and sdAbs with a high internalization rate induce more cell killing than sdAbs with a lower internalization rate in vitro. Even though the overall efficacy should also be tested in vivo, sdAbs are particularly interesting formats to be explored to obtain different internalization rates.

pH-Responsive Poly(styrene-alt-maleic anhydride) Alkylamide Copolymers for Intracellular Drug Delivery

2006 ◽  
Vol 7 (8) ◽  
pp. 2407-2414 ◽  
Author(s):  
Scott M. Henry ◽  
Mohamed E. H. El-Sayed ◽  
Christopher M. Pirie ◽  
Allan S. Hoffman ◽  
Patrick S. Stayton
Keyword(s):  
Drug Delivery ◽  
Maleic Anhydride ◽  
Ph Responsive ◽  
Intracellular Drug Delivery

pH-sensitive polyion complex micelles for tunable intracellular drug delivery

2015 ◽  
Vol 213 ◽  
pp. e55
Author(s):  
Jinjin Chen ◽  
Ying Zhang ◽  
Jianxun Ding ◽  
Chunsheng Xiao ◽  
Xiuli Zhuang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ph Sensitive ◽  
Polyion Complex ◽  
Polyion Complex Micelles ◽  
Intracellular Drug Delivery ◽  
Complex Micelles

Pillar[5]arene based supramolecular prodrug micelles with pH induced aggregate behavior for intracellular drug delivery

2015 ◽  
Vol 51 (14) ◽  
pp. 2999-3002 ◽  
Author(s):  
Yin Wang ◽  
Jianwei Du ◽  
Youxiang Wang ◽  
Qiao Jin ◽  
Jian Ji
Keyword(s):  
Drug Delivery ◽  
Acidic Condition ◽  
Ph Responsive ◽  
Intracellular Drug Delivery ◽  
Aggregate Behavior ◽  
Therapy Effect

A novel type of dual pH-responsive supramolecular prodrug micelles based on pillar[5]arene was prepared. It was found that the prodrug micelles could be aggregated upon acidic condition, which led to enhanced accumulation and better therapy effect.

Dual-Responsive Bola-Type Supra-Amphiphile Constructed from Water-Soluble Pillar[5]arene and Naphthalimide-Containing Amphiphile for Intracellular Drug Delivery

2017 ◽  
Vol 9 (5) ◽  
pp. 4843-4850 ◽  
Author(s):  
Xin Liu ◽  
Keke Jia ◽  
Yichen Wang ◽  
Wei Shao ◽  
Chenhao Yao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Water Soluble ◽  
Dual Responsive ◽  
Intracellular Drug Delivery

scholarly journals Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 237 ◽  
Author(s):  
Diti Desai ◽  
Malin Åkerfelt ◽  
Neeraj Prabhakar ◽  
Mervi Toriseva ◽  
Tuomas Näreoja ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Surface Charge ◽  
Silica Nanoparticles ◽  
Lipid Bilayers ◽  
Mesoporous Silica Nanoparticles ◽  
Cellular Level ◽  
Dependent Manner ◽  
Ethylene Imine ◽  
Intracellular Drug Delivery

Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were used: MSNs with a surface-grown poly(ethylene imine), PEI, coating only for hydrophobic cargo and MSNs with lipid bilayers covalently coupled to the PEI layer as a diffusion barrier for hydrophilic cargo. First, the effect of hydrophobicity corresponding to loading degree (hydrophobic cargo) as well as surface charge (hydrophilic cargo) on intracellular drug release was studied on the cellular level. All incorporated agents were able to release to varying degrees from the endosomes into the cytoplasm in a loading degree (hydrophobic) or surface charge (hydrophilic) dependent manner as detected by live cell imaging. When administered to organotypic 3D tumor models, the hydrophilic versus hydrophobic cargo-carrying MSNs showed remarkable differences in labeling efficiency, which in this case also corresponds to drug delivery efficacy in 3D. The obtained results could thus indicate design aspects to be taken into account for the development of efficacious intracellular drug delivery systems, especially in the translation from standard 2D culture to more biologically relevant organotypic 3D cultures.

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