Structural Deformation of MTX Induced by Nanodrug Conjugation Dictate Intracellular Drug Transport and Drug Efficacy

Park, Jun-Young; Hyun, Ja-Shil; Jee, Jun-Goo; Park, Sung Jean; Khang, Dongwoo

doi:10.2147/ijn.s317231

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…Fig. 6B shows two negative minima around 208 nm and 222 nm, suggesting that all proteins adopt the helical structure, similarly (Park et al 2021). The secondary structural composition calculated by the software, CDNN revealed more than 90% of the secondary components are α-helices, which is in good agreement with the predicted structure as shown in Fig.…”

Section: Structural Characteristic Of Grim-19supporting

confidence: 80%

Mass Production and Characterization of Recombinant Human Grim-19 in Escherichia coli

Subedi,

Park

2023

DTT

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The gene associated with retinoid-interferon-induced mortality 19 (Grim-19, also known as NADH dehydrogenase 1 α subunit 13) induces apoptotic cell death in response to interferon-β (IFN-β) and retinoic acid (RA) treatment. The Grim-19/ Stat3 complex suppresses the essential genes that enhance cell growth. In addition, Grim-19 inhibits oncoproteins and viral gene products during tumorigenesis, which suggests that the development of biologics of Grim-19 could be considered. Although various cellular functions of Grim-19 were identified, limited information on the structural characteristics of Grim-19 is available. To study the structural characteristics of Grim-19 and to discover the possible biologics of Grim-19, the preparation of a large amount of Grim-19 is necessary. Grim-19 is the subunit of the mitochondrial membrane protein, ubiquinone, which is also found in the nucleus and cytoplasm. Thus, the stable recombinant protein of Grim-19 is not easily obtainable because of the aggregation of the protein. Here we successfully established an efficient expression system in E. coli by designing various E. coli vectors. Most of the E. coli vectors showed acceptable expression levels of Grim-19 in E. coli while they mainly produced an insoluble form of Grim-19 which could not be refolded sufficiently in vitro. Only the NusA-tagged Grim-19 fusion protein can be obtained as the soluble form in E. coli. The CD analysis showed Grim-19 mainly contains the α-helical structure with a melting temperature, 47℃.

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Section: Structural Characteristic Of Grim-19supporting

confidence: 80%

Mass Production and Characterization of Recombinant Human Grim-19 in Escherichia coli

Subedi,

Park

2023

DTT

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“…The literature has shown that covalent conjugation of CNT-DOX in intracellular trafficking assays represents a more stable drug conjugation style in intracellular drug delivery systems [ 35 ]. In this study, intracellular drug delivery analysis showed that early endosome (EE) and LE signal intensities were analyzed in normal lung cancer cells (A549 and H446 cells) and multidrug-resistant SCLC cells (H69AR cells) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Overcoming multidrug-resistant lung cancer by mitochondrial-associated ATP inhibition using nanodrugs

et al. 2023

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Despite the development of therapeutic modalities to treat cancer, multidrug resistance (MDR) and incomplete destruction of deeply embedded lung tumors remain long-standing problems responsible for tumor recurrence and low survival rates. Therefore, developing therapeutic approaches to treat MDR tumors is necessary. In this study, nanodrugs with enhanced intracellular drug internalization were identified by the covalent bonding of carbon nanotubes of a specific nano size and doxorubicin (DOX). In addition, carbon nanotube conjugated DOX (CNT-DOX) sustained in the intracellular environment in multidrug-resistant tumor cells for a long time causes mitochondrial damage, suppresses ATP production, and results in the effective therapeutic effect of drug-resistant tumors. This study identified that H69AR lung cancer cells, an adriamycin (DOX) drug-resistant tumor cell line, did not activate drug resistance function on designed nano-anticancer drugs with a specific nano size. In summary, this study identified that the specific size of the nanodrug in combination with DOX overcame multidrug-resistant tumors by inducing selective accumulation in tumor cells and inhibiting ATP by mitochondrial damage.

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“…Modifications in the structural variants of MTX enhanced the anti-inflammatory drug effectiveness of human fibroblast like synovial cells (FLS) through sustained extracellular drug release and burst drug release beneath intracellular state. 69 Moreover, methotrexate (MTX) has adverse side effects such as gastrointestinal complications and hepatotoxicity leading to MTX discontinuation. Subsequently, a highpressure carbon monoxide synthesized single-walled carbon nanotubes (HiPco-SWCNTs) and carboxyl-SWCNTs combined with a small interfering RNA (siRNA) targeting NOTCH1gene are examined as drug carrier for methotrexate.…”

Section: Effective Utilization and Outcomes Of Carbon Nanotubes In Dr...mentioning

confidence: 99%

Carbon Nanotubes: An Optimistic Nanomaterial with Superfluity Characteristics in Drug Delivery for the Treatment of Arthritis

Srinivasan¹,

Palanisamy²

2022

Ind. J. Pharm. Edu. Res

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Arthritis is chronic disease that affects the joint system and induces pain and inflammation in human body. Nanotechnology based drug delivery has progressed to be viable and more attractive for the treatment of arthritis. A carbon nanotube is one of the foremost prominent nanomaterials with high surface area utilized to exhibit stable release of drugs. Nonetheless, researchers have done investigations using either single-walled carbon nanotubes (SWCNT) or multi-walled carbon nanotubes (MWCNT) to gain optimistic results in targeted delivery for arthritis disorder. In this view, functionalized carbon nanotubes are employed to deliver drugs with higher accuracy and controlled release of drugs with less toxic effects. Unfortunately, very limited investigations are reported the prospective utilization of functionalized carbon nanotubes as eminent drug carriers for arthritis treatment. Moreover, the amounts of toxicity of carbon nanotubes, as well as their aggregation in cells and tissues are the key limits that must be considered evidently. The biosafety exposure of carbon nanotubes to humans are still a source of concern. As a result, more research is needed to solve the obstacles associated with carbon nanotubes in conjugation with drugs such as agglomeration, lack of solubility and interaction mechanism with drugs. In this review, we discussed the significant characteristics and outcomes of carbon nanotubes in drug delivery for the treatment of arthritis disease. The toxic level of carbon nanotubes is projected and why the incorporation of CNTs in drug delivery is still limited in various phases is highlighted. The biosafety aspects, cellular uptake mechanism and the importance of functionalization carbon nanotubes in drug delivery are reviewed.

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Structural Deformation of MTX Induced by Nanodrug Conjugation Dictate Intracellular Drug Transport and Drug Efficacy

Cited by 6 publications

References 43 publications

Mass Production and Characterization of Recombinant Human Grim-19 in Escherichia coli

Mass Production and Characterization of Recombinant Human Grim-19 in Escherichia coli

Overcoming multidrug-resistant lung cancer by mitochondrial-associated ATP inhibition using nanodrugs

Carbon Nanotubes: An Optimistic Nanomaterial with Superfluity Characteristics in Drug Delivery for the Treatment of Arthritis

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