Biodistribution and molecular studies on orally administered nanoparticle-AON complexes encapsulated with alginate aiming at inducing dystrophin rescue in mdx mice.
Biodistribution and molecular studies on orally administered nanoparticle-AON complexes encapsulated with alginate aiming at inducing dystrophin rescue in mdx mice.
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对口服纳米颗粒腹部复合物的生物分布和分子研究，旨在诱导MDX小鼠诱导肌营养不良蛋白营救的藻酸盐。
DOI：
10.1155/2013/527418
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发表时间：
2013
影响因子：
--
通讯作者：
Ferlini A
中科院分区：
文献类型：
--
作者：
Falzarano MS;Passarelli C;Bassi E;Fabris M;Perrone D;Sabatelli P;Maraldi NM;Donà S;Selvatici R;Bonaldo P;Sparnacci K;Laus M;Braghetta P;Rimessi P;Ferlini A
我们先前已经证明，腹膜内注射吸附在阳离子核-壳纳米颗粒（称为ZM 2）上的2′-O-甲基硫代磷酸酯（2′OMePS）反义寡核苷酸，可引起mdx小鼠肌肉中肌营养不良蛋白的恢复。本工作的目的是评估口服途径作为ZM 2-反义寡核苷酸复合物的替代给药方式。在单次和多次口服剂量的IR-染料缀合的纳米颗粒后，评价纳米颗粒的生物分布和消除。通过Odyssey红外成像系统在体内以及组织冷冻切片、尿液和粪便中追踪标记的纳米颗粒，并显示在肠道和腹部淋巴结中的持久性为72小时至7天，然后被消除。我们随后测试了无藻酸盐和藻酸盐包封的ZM 2-反义寡核苷酸（AON）复合物，分别在mdx小鼠中每周口服给药2次和3次，共12周。用藻酸盐ZM 2-AON处理在隔膜和肠平滑肌中诱导轻微的肌营养不良蛋白拯救，而在无藻酸盐ZM 2-AON处理的小鼠中没有检测到肌营养不良蛋白。这些数据鼓励进一步的实验口服给药测试NP和AON复合物，可能翻译的寡核糖核苷酸介导的分子疗法。
We have previously demonstrated that intraperitoneal injections of 2′-O-methyl-phosphorothioate (2′OMePS) antisense oligoribonucleotides adsorbed onto a cationic core-shell nanoparticles (NPs), termed ZM2, provoke dystrophin restoration in the muscles of mdx mice. The aim of the present work was to evaluate the oral route as an alternative way of administration for ZM2-antisense oligoribonucleotides complexes. The biodistribution and elimination of nanoparticles were evaluated after single and multiple oral doses of IR-dye conjugated nanoparticles. Labeled nanoparticles were tracked in vivo as well as in tissue cryosections, urines and feces by Odyssey infrared imaging system, and revealed a permanence in the intestine and abdominal lymph nodes for 72 hours to 7 days before being eliminated. We subsequently tested alginate-free and alginate-encapsulated ZM2-antisense oligoribonucleotides (AON) complexes orally administered 2 and 3 times per week, respectively, in mdx mice for a total of 12 weeks. Treatment with alginate ZM2-AON induced a slight dystrophin rescue in diaphragm and intestine smooth muscles, while no dystrophin was detected in alginate-free ZM2-AON treated mice. These data encourage further experiments on oral administration testing of NP and AON complexes, possibly translatable in oligoribonucleotides-mediated molecular therapies.
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影响因子：
12.4
作者：
Heemskerk, Hans;de Winter, Christa;van Kuik, Petra;Heuvelmans, Niki;Sabatelli, Patrizia;Rimessi, Paola;Braghetta, Paola;van Ommen, Gert-Jan B.;de Kimpe, Sjef;Ferlini, Alessandra;Aartsma-Rus, Annemieke;van Deutekom, Judith C. T.
通讯作者：
van Deutekom, Judith C. T.
影响因子：
158.5
作者：
Goemans, Nathalie M.;Tulinius, Mar;van Deutekom, Judith C.
通讯作者：
van Deutekom, Judith C.
影响因子：
3.7
作者：
Ferreiro, MG;Tillman, LG;Bodmeier, R
通讯作者：
Bodmeier, R
影响因子：
3.5
作者：
Heemskerk, Hans A.;de Winter, Christa L.;Aartsma-Rus, Annemieke
通讯作者：
Aartsma-Rus, Annemieke
影响因子：
14
作者：
Kavimandan, NJ;Losi, E;Peppas, NA
通讯作者：
Peppas, NA