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Nanoaggregate-forming lipid-conjugated AS1411 aptamer as a promising tumor-targeted delivery system of anticancer agents in vitro
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2021-06-24 , DOI: 10.1016/j.nano.2021.102429
Josué Carvalho 1 , Jéssica Lopes-Nunes 1 , Brune Vialet 2 , Tiago Rosado 3 , Eugenia Gallardo 1 , João Vale 4 , Catarina Eloy 5 , Sofia Ferreira 6 , Rita Palmeira-de-Oliveira 7 , Maria Paula Cabral Campello 8 , António Paulo 8 , Philippe Barthélémy 2 , Jean-Louis Mergny 9 , Gilmar F Salgado 2 , João A Queiroz 1 , Andrew D Ellington 10 , Carla Cruz 1
Affiliation  

Nanoparticles offer targeted delivery of drugs with minimal toxicity to surrounding healthy tissue and have great potential in the management of human papillomavirus (HPV)-related diseases. We synthesized lipid-modified AS1411 aptamers capable of forming nanoaggregates in solution containing Mg2+. The nanoaggregates presented suitable properties for pharmaceutical applications such as small size (100 nm), negative charge, and drug release. The nanoaggregates were loaded with acridine orange derivative C8 for its specific delivery into cervical cancer cell lines and HPV-positive tissue biopsies. This improved inhibition of HeLa proliferation and cell uptake without significantly affecting healthy cells. Finally, the nanoaggregates were incorporated in a gel formulation with promising tissue retention properties aiming at developing a local delivery strategy of the nanoaggregates in the female genital tract. Collectively, these findings suggest that the nanoformulation protocol has great potential for the delivery of both anticancer and antiviral agents, becoming a novel modality for cervical cancer management.



中文翻译:

纳米聚集体形成脂质缀合的 AS1411 适体作为一种有前途的体外抗癌药物靶向肿瘤递送系统

纳米颗粒提供靶向递送药物,对周围健康组织的毒性最小,并且在管理人乳头瘤病毒 (HPV) 相关疾病方面具有巨大潜力。我们合成了脂质修饰的 AS1411 适体,能够在含有 Mg 2+的溶液中形成纳米聚集体。纳米聚集体呈现出适合药物应用的特性,例如小尺寸(100 nm)、负电荷和药物释放。纳米聚集体负载吖啶橙衍生物 C 8因其特异性递送至宫颈癌细胞系和 HPV 阳性组织活检。这改善了对 HeLa 增殖和细胞摄取的抑制,而不会显着影响健康细胞。最后,将纳米聚集体掺入具有良好组织保留特性的凝胶制剂中,旨在开发纳米聚集体在女性生殖道中的局部递送策略。总的来说,这些研究结果表明,纳米制剂方案在递送抗癌剂和抗病毒剂方面具有巨大潜力,成为宫颈癌治疗的一种新方式。

更新日期:2021-07-14
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