The role of high‐density lipoproteins in antitumor drug delivery

Sarhadi, Susan; Ganjali, Shiva; Pirro, Matteo; Sahebkar, Amirhossein

doi:10.1002/iub.2105

Cited by 6 publications

(5 citation statements)

References 77 publications

(152 reference statements)

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“…Over a 27‐year follow‐up period, TG levels >5 mmol/L (440 mg/dl) and <1 mmol/L (88 mg/dl) were associated with 17‐ and 5‐fold risks of myocardial infarction 14 . As the smallest and densest of the plasma lipoproteins, high‐density lipoprotein (HDL) has been identified as a major recipient of free cholesterol and reversed cholesterol transport 15 . HDL also performs functions such as the promotion of cholesterol efflux from macrophages, antioxidant activity, inhibition of vascular inflammation, and improvement of endothelial function 16 .…”

Section: Discussionmentioning

confidence: 99%

Predictive value of the atherogenic index of plasma for chronic total occlusion before coronary angiography

Liu

et al. 2021

Clinical Cardiology

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Background The atherogenic index of plasma (AIP) is calculated by logarithmic transformation of the ratio of triglyceride (TG) and high‐density lipoprotein cholesterol (HDL‐C) concentrations. Although previous studies have demonstrated that the AIP is associated with coronary artery disease, its association with chronic total occlusion (CTO) requires elucidation. Hypothesis We hypothesized that the AIP would have diagnostic value in cases of CTO and could be used to predict adverse events. Methods This study involved 1131 inpatients who underwent coronary angiography. Data on demographic and clinical characteristics, coronary artery stenosis rated by the Gensini score, and clinical assessment by the Global Registry of Acute Coronary Events and thrombolysis in myocardial infarction (TIMI) scores were collected by cardiovascular doctors. Serum AIP values were evaluated by logarithmic transformation of the ratio of TG and HDL‐C concentrations. The correlations of AIP values with clinical parameters were assessed, and receiver‐operating characteristic curves were constructed for CTO diagnosis. Results Overall, 1131 inpatients were assigned to the CTO (n = 398) and control (n = 733) groups. Compared with the control group, the CTO group showed a significantly higher AIP (p < .05). The AIP was positively correlated with body mass index, the TIMI score, the Gensini score, and stent length and was effective for the diagnosis and risk assessment of patients with CTO. Multivariate logistic regression analyses revealed that the AIP was an independent risk factor for CTO. The findings suggest that the AIP could predict the presence of CTO and disease severity.

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Section: Discussionmentioning

confidence: 99%

Predictive value of the atherogenic index of plasma for chronic total occlusion before coronary angiography

Liu

et al. 2021

Clinical Cardiology

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“…Thus, in contrast to their ability to curb early payload release in the cell-free environment of a buffer solution, the mannose-coated rHDL NPs were effective in delivering DMXAA to the macrophages. Together with the natural intratumoral accumulation of HDL-type nanoparticles [ 70 , 94 , 95 ], this selective release of the payload to the ID8 CM-educated RAW 264.7 macrophages underscores the potential of the rHDL-DPM NPs in improving therapeutic payload bioavailability at the tumor site. Furthermore, the rHDL-DPM NPs were more efficient at delivering their payload to the ID8 CM-educated macrophages than to the ID8 cells.…”

Section: Discussionmentioning

confidence: 99%

Mannose-Coated Reconstituted Lipoprotein Nanoparticles for the Targeting of Tumor-Associated Macrophages: Optimization, Characterization, and In Vitro Evaluation of Effectiveness

et al. 2023

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Reconstituted high-density lipoprotein nanoparticles (rHDL NPs) have been utilized as delivery vehicles to a variety of targets, including cancer cells. However, the modification of rHDL NPs for the targeting of the pro-tumoral tumor-associated macrophages (TAMs) remains largely unexplored. The presence of mannose on nanoparticles can facilitate the targeting of TAMs which highly express the mannose receptor at their surface. Here, we optimized and characterized mannose-coated rHDL NPs loaded with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an immunomodulatory drug. Lipids, recombinant apolipoprotein A-I, DMXAA, and different amounts of DSPE-PEG-mannose (DPM) were combined to assemble rHDL-DPM-DMXAA NPs. The introduction of DPM in the nanoparticle assembly altered the particle size, zeta potential, elution pattern, and DMXAA entrapment efficiency of the rHDL NPs. Collectively, the changes in physicochemical characteristics of rHDL NPs upon the addition of the mannose moiety DPM indicated that the rHDL-DPM-DMXAA NPs were successfully assembled. The rHDL-DPM-DMXAA NPs induced an immunostimulatory phenotype in macrophages pre-exposed to cancer cell-conditioned media. Furthermore, rHDL-DPM NPs delivered their payload more readily to macrophages than cancer cells. Considering the effects of the rHDL-DPM-DMXAA NPs on macrophages, the rHDL-DPM NPs have the potential to serve as a drug delivery platform for the selective targeting of TAMs.

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“…In 2012, through a combination of small-scale clinical trials and animal experiments, we demonstrated that aging may promote cardiac apoptosis, a significant cause of ischemia-induced heart failure [ 4 ]. Peitan L et al’s study found that Bax mRNA / Bcl-2 mRNA and apoptosis rate are higher in aged mice compared to the young with the establishment of coronary artery ischemia/reperfusion model [ 18 ]. Data from several studies also proved this conclusion [ 5 , 6 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Increased cytochrome C threonine 50 phosphorylation in aging heart as a novel defensive signaling against hypoxia/reoxygenation induced apoptosis

Sun

Lin

et al. 2022

Aging

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Previous studies have shown that aging promotes myocardial apoptosis. However, the detailed mechanisms remain unclear. Our recent studies revealed that aging not only activates apoptosis, but also activates some antiapoptotic factors. By quantitative phosphoproteomics, here we demonstrated that aging increases cytochrome c (Cytc) phosphorylation at threonine 50 (T50), a post-translational modification with unknown functional impact. With point mutation and lentivirus transfection, cardiomyocytes were divided into four groups: empty vector group, WT (wild type), T50E (as a phosphomimic variant), and T50A (non-phosphorylatable). TUNEL staining and flow cytometry were used to determine the apoptosis ratio in different groups after hypoxic/reoxygenated (H/R) treatment. The results showed that T50-phosphorylated Cytc suppressed myocardial apoptosis induced by H/R. Furthermore, Western Blot and ELISA measurements revealed that Cytc T50 phosphorylation inhibited caspase-9 and caspase-3 activity without altering caspase-8, BCL-2, BCL-XL, and Bax expression. In our study, we demonstrated that aging increases phosphorylation Cytc at T50 and this aging-increasing phosphorylation site can suppress H/R-induced apoptosis.

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The role of high‐density lipoproteins in antitumor drug delivery

Cited by 6 publications

References 77 publications

Predictive value of the atherogenic index of plasma for chronic total occlusion before coronary angiography

Predictive value of the atherogenic index of plasma for chronic total occlusion before coronary angiography

Mannose-Coated Reconstituted Lipoprotein Nanoparticles for the Targeting of Tumor-Associated Macrophages: Optimization, Characterization, and In Vitro Evaluation of Effectiveness

Increased cytochrome C threonine 50 phosphorylation in aging heart as a novel defensive signaling against hypoxia/reoxygenation induced apoptosis

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