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Cuboidal tethered cyclodextrin frameworks tailored for hemostasis and injured vessel targeting.

ABSTRACT: Rationale: Targeted delivery of therapeutic drugs or imaging agents to injured blood vessels via nanocarriers is likely to be dependent on the particle shape, yet cubic nanoparticle carriers have not been reported for vascular targeting. Here, we demonstrate that cuboidal cyclodextrin frameworks possess superior hemostasis effect and injured vessels targeting compared with spherical counterpart. Methods: Cuboidal and biocompatible γ-cyclodextrin metal-organic frameworks (CD-MOFs) are synthesized, tethered via crosslinking and surface modification with GRGDS peptide (GS5-MOFs). The specific interactions of cubic GS5-MOF nanoparticles with activated platelets were investigated by in vitro platelet aggregation assay and atomic force microscopy measurements (AFM). The hemostatic capacity and injured vessel targeting efficacy were evaluated in vivo. Results: Cuboidal GS5-MOF nanoparticles exhibit enhanced adhesion and aggregation with activated platelets in vitro under static condition and a physiologically relevant flow environment. The cubic GS5-MOF nanoparticles show efficient hemostatic effects with bleeding time and blood loss decrease of 90% and strong injured vessel targeting in vivo, markedly superior to spherical γ-CD nanosponges with the same chemical composition. Conclusions: These results clearly highlight the contribution of the cuboidal shape of GS5-MOFs to the enhanced aggregation of activated platelets and high targeting to damaged vessels. The cuboidal nanoparticle system provides an innovative delivery platform for the treatment and diagnosis of vascular diseases.

SUBMITTER: He Y

PROVIDER: S-EPMC6525997 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The cause of lacunar ischemic stroke, a clinical feature of cerebral small vessel disease (SVD), is largely unknown. Inflammation and endothelial dysfunction have been implicated. Plasma biomarkers could provide mechanistic insights but current data are conflicting. White matter hyperintensities (WMHs) are an important imaging biomarker of SVD. It is unknown if plasma biomarkers add predictive capacity beyond age and vascular risk factors in explaining WMH.We prospectively recruited patients presenting with non-disabling ischemic stroke, classifying them clinically and with the help of MRI as lacunar or cortical. We measured biomarkers of inflammation, endothelial dysfunction and hemostasis for >1 month after stroke and compared biomarker levels between stroke subtypes. We quantitatively calculated WMH. We used multiple linear regression analysis to model WMH as a function of age, sex, hypertension and smoking (the baseline model). We fitted exploratory models using plasma biomarkers as predictor variables to assess model improvement over baseline.We recruited 125 patients. The lacunar group (n = 65) had lower tissue plasminogen activator (t-PA) levels in unadjusted (7.39 vs. 8.59 ng/ml, p = 0.029) and adjusted (p = 0.035) analyses compared with the cortical group (n = 60). There were no significant differences in the other plasma biomarkers. The results for t-PA were consistent with an updated meta-analysis, although the effect remains non-significant (standardized mean difference -0.08 (95% CI -0.25 to 0.09)). The baseline regression model explained 29% of the variance in quantitative WMH (R2 0.289). Inflammatory biomarkers showed minor improvement over baseline (R2 0.291), but the other plasma biomarkers did not improve the baseline model.Plasma t-PA levels appear to differ between lacunar and cortical stroke subtypes, late after stroke, independent of age, sex and vascular risk factors and may reflect endothelial dysfunction. Except for a minor additional predictive effect of inflammatory markers, plasma biomarkers do not relate to WMH severity in this small stroke population.

Project description:Importance:Vessel-sealant devices (VSDs) have been popularized for use in thyroid operations; however, the association of their use with postoperative neck hematoma, a rare but potentially fatal complication, has not been well studied. Objective:To examine the association of VSDs vs conventional hemostasis (CH) in thyroid operations with the development of neck hematoma. Design, Setting, and Participants:This retrospective cohort study evaluated 10?903 patients in the Thyroid Procedure-Targeted Database of the National Surgical Quality Improvement Program from January 1, 2016, to December 31, 2017. One-to-one nearest-neighbor propensity score matching was conducted to adjust for differences in baseline covariates, including demographics, comorbidities, indications for thyroid procedure (goiter, Graves disease, malignant and benign thyroid nodule), and several other thyroid-specific characteristics, between the VSD and CH groups. Main Outcomes and Measures:The primary outcome was postoperative hematoma requiring intervention with open evacuation, return to the operating room, tracheostomy, additional observation, or extended length of stay. Secondary outcomes include recurrent laryngeal nerve injury, operative duration, and hospital length of stay. Results:One-to-one propensity score matching yielded 6522 patients (mean [SD] age, 52 [15] years; 8544 [78.4%] female) with 3261 in each exposure group such that distribution of observed baseline covariates was not different between groups of the same propensity score. Within the matched cohort, CH was associated with higher odds of neck hematoma compared with VSD (odds ratio, 2.33; 95% CI, 1.55-3.49; P?<?.001), with 34 (1.0%) hematomas in the VSD group and 78 (2.4%) in the CH group. On the basis of this analysis, the number needed to treat with a VSD to prevent 1 postoperative hematoma was 74. Secondary outcomes included longer length of hospital stay (incidence rate ratio, 1.29; 95% CI, 1.23-1.36; P?<?.001]) in the CH group compared with the VSD group but no difference in the odds of recurrent laryngeal nerve injury (odds ratio, 0.90; 95% CI, 0.73-1.11; P?=?.32) or operative duration (incidence rate ratio, 0.99; 95% CI, 0.96-1.01; P?=?.24). Conclusions and Relevance:Use of VSDs during thyroid operations was associated with reduced odds of neck hematoma compared with CH techniques without increasing odds of nerve injury. The results suggest that postoperative neck hematoma rates after thyroid surgery may differ based on the hemostasis technique and that these differences should be considered when developing strategies for quality improvement of postoperative outcomes.

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Cuboidal tethered cyclodextrin frameworks tailored for hemostasis and injured vessel targeting.

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