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Multifunctional cationic nanosystems for nucleic acid therapy of thoracic aortic dissection.

ABSTRACT: Thoracic aortic dissection (TAD) is an aggressive vascular disease that requires early diagnosis and effective treatment. However, due to the particular vascular structure and narrowness of lesion location, there are no effective drug delivery systems for the therapy of TAD. Here, we report a multifunctional delivery nanosystem (TP-Gd/miRNA-ColIV) composed of gadolinium-chelated tannic acid (TA), low-toxic cationic PGEA (ethanolamine-aminated poly(glycidyl methacrylate)) and type IV collagen targeted peptide (ColIV) for targeted nucleic acid therapy, early diagnosis and noninvasive monitoring of TAD. Such targeted therapy with miR-145 exhibits impressive performances in stabilizing the vascular structures and preventing the deterioration of TAD. After the treatment with TP-Gd/miR-145-ColIV, nearly no dissection occurs in the thoracic aortic arches of the mice with TAD model. Moreover, TP-Gd/miRNA-ColIV also demonstrates good magnetic resonance imaging (MRI) ability and can be used to noninvasively monitor the development conditions of TAD.

SUBMITTER: Xu C

PROVIDER: S-EPMC6639375 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Multifunctional cationic nanosystems for nucleic acid therapy of thoracic aortic dissection.

Xu Chen C Zhang Yanzhenzi Y Xu Ke K Nie Jing-Jun JJ Yu Bingran B Li Sijin S Cheng Gang G Li Yulin Y Du Jie J Xu Fu-Jian FJ

Nature communications 20190718 1

Thoracic aortic dissection (TAD) is an aggressive vascular disease that requires early diagnosis and effective treatment. However, due to the particular vascular structure and narrowness of lesion location, there are no effective drug delivery systems for the therapy of TAD. Here, we report a multifunctional delivery nanosystem (TP-Gd/miRNA-ColIV) composed of gadolinium-chelated tannic acid (TA), low-toxic cationic PGEA (ethanolamine-aminated poly(glycidyl methacrylate)) and type IV collagen tar ...[more]

PMID: 31320641

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Project description:BackgroundRetrograde type A aortic dissection (RTAD) is a rare but life-threatening complication after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). A graft inversion technique was applied to distal anastomosis in total arch replacement for this complicated dissection. We reviewed our results of the processing for this serious complication. The aim is to evaluate the feasibility of this technology.MethodsFrom January 2013 to December 2017, 20 patients (80% male, mean age 50.9 ± 9.5 years) with retrograde type A aortic dissection after thoracic endovascular aortic repair for type B aortic dissection were scheduled for surgical treatment at our center. All patients underwent an ascending aorta and total aortic arch replacement procedure. The 20 patients were divided into two groups, 1 group involved 9 patients underwent surgery using stepwise technique; the graft inversion technique was performed in the other group containing the remaining 11 patients. The postoperative variables, including cardiopulmonary bypass time, the circulatory arrest time, the aortic cross clamp time, were analyzed. Meanwhile we also analyzed the postoperative mortality and complications to evaluate the early and mid-term outcomes of surgical treatment for RTAD after TEVAR.ResultsIn-hospital mortality was 10% (2 of 20 patients). No patient developed postoperative paraplegia, renal failure, stroke, or distal anastomotic bleeding. Two patients developed renal insufficiency, one developed neurologic insufficiency, and one developed pulmonary infection, all of which were managed accordingly. Cardiopulmonary bypass (CPB) time, and circulatory arrest time were significantly shorter in the graft inversion group than in the stepwise group (165.8 ± 37.9 min versus 206.1 ± 46.8 min, p<0.05; 34.5 ± 5.6 min versus 42.4 ± 9.5 min, p<0.05, respectively). The 18 survivors had a mean follow-up of 25.8 ± 18.2 months, and all patients remained alive and well.ConclusionGraft inversion can enable a secure distal anastomosis under good surgical exposure, resulting in reduced durations of CPB, and circulatory arrest for RTAD after TEVAR. Surgical treatment could be a safe alternative for treatment of this patients.

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Multifunctional cationic nanosystems for nucleic acid therapy of thoracic aortic dissection.

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Multifunctional cationic nanosystems for nucleic acid therapy of thoracic aortic dissection.

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