Abstract:In the present study, the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers of around 20 nm. The characterization study shows metallic AuNPs with MTX polydispersed on the surface. MTX is linked by the replacement of citrate by the MTX carboxyl group. The drug release profiles show faster MTX release when it is conjugated, which leads to the best control of plasma concentration. Moreover, the enhanced rel… Show more
“…However, high doses of MTX usually lead to serious side effects. Nowadays, some carriers have been loaded with MTX to improve drug safety ( 35 - 37 ). Desipramine, an antidepressant, is commonly used in combination regimens, not only helping to relieve depression but also enhancing the cytotoxicity of the platinum agents ( 38 ).…”
Background: Autophagy inhibits tumorigenesis by limiting inflammation. Various lncRNAs are associated with tumour biological processes, including lung adenocarcinoma (LUAD), but the role of autophagyrelated lncRNAs (ARlncRNAs) in LUAD has not been fully elucidated. Thus, this study aimed to construct a prognostic signature based on ARlncRNAs for LUAD.
Methods:The RNA-seq (FPKM) data and clinical information of LUAD patients were downloaded fromThe Cancer Genome Atlas (TCGA) database. After differentially expressed lncRNAs in tumour and normal groups were identified, cox regression analyses were performed to construct a prognostic signature which was then assessed through independent prognostic analysis and functional enrichment analysis. Moreover, based on the mRNAs co-expressed with the ARlncRNAs, several potential small molecule drugs were explored in the Connectivity map (Cmap).Results: A signature consisting of seven ARlncRNAs (FAM83A−AS1, LINC01116, ILF3-DT, EBLN3P, AL161785.1, AC092279.1 and AC026355.2) was constructed to predict overall survival (OS) for LUAD.The signature was identified to be independent by the cox regression analysis and obtained the largest area under the curve (AUC =0.721) in the ROC. Six small molecule drugs (MS-275, methotrexate, desipramine, benzbromarone, rifampicin and doxazosin) were selected from Cmap.Conclusions: A novel ARlncRNA signature for LUAD prognostic prediction was constructed, which had better efficacy than the TNM stage and used to propose potential therapeutic regimens for LUAD patients.
“…However, high doses of MTX usually lead to serious side effects. Nowadays, some carriers have been loaded with MTX to improve drug safety ( 35 - 37 ). Desipramine, an antidepressant, is commonly used in combination regimens, not only helping to relieve depression but also enhancing the cytotoxicity of the platinum agents ( 38 ).…”
Background: Autophagy inhibits tumorigenesis by limiting inflammation. Various lncRNAs are associated with tumour biological processes, including lung adenocarcinoma (LUAD), but the role of autophagyrelated lncRNAs (ARlncRNAs) in LUAD has not been fully elucidated. Thus, this study aimed to construct a prognostic signature based on ARlncRNAs for LUAD.
Methods:The RNA-seq (FPKM) data and clinical information of LUAD patients were downloaded fromThe Cancer Genome Atlas (TCGA) database. After differentially expressed lncRNAs in tumour and normal groups were identified, cox regression analyses were performed to construct a prognostic signature which was then assessed through independent prognostic analysis and functional enrichment analysis. Moreover, based on the mRNAs co-expressed with the ARlncRNAs, several potential small molecule drugs were explored in the Connectivity map (Cmap).Results: A signature consisting of seven ARlncRNAs (FAM83A−AS1, LINC01116, ILF3-DT, EBLN3P, AL161785.1, AC092279.1 and AC026355.2) was constructed to predict overall survival (OS) for LUAD.The signature was identified to be independent by the cox regression analysis and obtained the largest area under the curve (AUC =0.721) in the ROC. Six small molecule drugs (MS-275, methotrexate, desipramine, benzbromarone, rifampicin and doxazosin) were selected from Cmap.Conclusions: A novel ARlncRNA signature for LUAD prognostic prediction was constructed, which had better efficacy than the TNM stage and used to propose potential therapeutic regimens for LUAD patients.
“…This is because they can efficiently localize MTX to the inflamed joints by taking advantage of the leaky vasculature in these tissues. Indeed, various MTX-loaded nanoparticles based on liposomes, , proteins, , and organic , and inorganic components have been developed to improve therapeutic outcomes relative to free MTX. The data of Figure B,C show that the pCaSiNP construct also effectively accumulated in the regions of the inflamed joints.…”
The lack of drugs that target both disease progression
and tissue
preservation makes it difficult to effectively manage rheumatoid arthritis
(RA). Here, we report a porous silicon-based nanomedicine that efficiently
delivers an antirheumatic drug to inflamed synovium while degrading
into bone-remodeling products. Methotrexate (MTX) is loaded into the
porous silicon nanoparticles using a calcium silicate based condenser
chemistry. The calcium silicate–porous silicon nanoparticle
constructs (pCaSiNPs) degrade and release the drug preferentially
in an inflammatory environment. The biodegradation products of the
pCaSiNP drug carrier are orthosilicic acid and calcium ions, which
exhibit immunomodulatory and antiresorptive effects. In a mouse model
of collagen-induced arthritis, systemically administered MTX-loaded
pCaSiNPs accumulate in the inflamed joints and ameliorate the progression
of RA at both early and established stages of the disease. The disease
state readouts show that the combination is more effective than the
monotherapies.
“…Some drugs with specific groups can directly link with AuNPs, such as methotrexate (MTX) with carboxylic groups. 37 Even the simplest conjugate (MTX-AuNPs) also showed enhanced cytotoxic effect against cancer cells, while free MTX exhibited reduced anticancer effect at equal doses. 37 , 38 Figure 3 Intracellular distribution of free DOX and Au-SS-DOX in HepG2-R cells.…”
Section: Aunps In Cancer Therapymentioning
confidence: 99%
“… 37 Even the simplest conjugate (MTX-AuNPs) also showed enhanced cytotoxic effect against cancer cells, while free MTX exhibited reduced anticancer effect at equal doses. 37 , 38 Figure 3 Intracellular distribution of free DOX and Au-SS-DOX in HepG2-R cells. Confocal images of cells treated with ( A ) free DOX and ( B ) Au-SS-DOX showing distribution of DOX-derived fluorescence (red).…”
Cancer is the second leading cause of death in the world, behind only cardiovascular diseases, and is one of the most serious diseases threatening human health nowadays. Cancer patients’ lives are being extended by the use of contemporary medical technologies, such as surgery, radiotherapy, and chemotherapy. However, these treatments are not always effective in extending cancer patients’ lives. Simultaneously, these approaches are often accompanied with a series of negative consequences, such as the occurrence of adverse effects and an increased risk of relapse. As a result, the development of a novel cancer-eradication strategy is still required. The emergence of nanomedicine as a promising technology brings a new avenue for the circumvention of limitations of conventional cancer therapies. Gold nanoparticles (AuNPs), in particular, have garnered extensive attention due to their many specific advantages, including customizable size and shape, multiple and useful physicochemical properties, and ease of functionalization. Based on these characteristics, many therapeutic and diagnostic applications of AuNPs have been exploited, particularly for malignant tumors, such as drug and nucleic acid delivery, photodynamic therapy, photothermal therapy, and X-ray-based computed tomography imaging. To leverage the potential of AuNPs, these applications demand a comprehensive and in-depth overview. As a result, we discussed current achievements in AuNPs in anticancer applications in a more methodical manner in this review. Also addressed in depth are the present status of clinical trials, as well as the difficulties that may be encountered when translating some basic findings into the clinic, in order to serve as a reference for future studies.
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