Liposomal siRNA nanocarriers for cancer therapy.
Liposomal siRNA nanocarriers for cancer therapy.
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DOI：
10.1016/j.addr.2013.12.008
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发表时间：
2014-02
影响因子：
16.1
通讯作者：
Lopez-Berestein G
中科院分区：
文献类型：
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作者：
Ozpolat B;Sood AK;Lopez-Berestein G
小干扰rna （Small interfering rna, siRNA）是近年来出现的一种新的治疗方法，在癌症和其他疾病的治疗方面具有巨大的潜力。一种特殊设计的siRNA结合并诱导靶基因（mRNA）转录后沉默。基于sirna的治疗药物的临床应用受到其快速降解、细胞摄取不良和全身给药后肾脏清除迅速的限制。由脂质、聚合物和金属组成的各种合成和天然纳米颗粒已被开发用于siRNA递送，具有不同的功效和安全性。通过提高稳定性和生物利用度，脂质体纳米颗粒已被证明可以有效地将siRNA递送到肿瘤组织中。虽然提供高转染效率和与带负电荷的siRNA形成复合物的能力，但阳离子脂质体/脂质体具有高毒性。另一方面，带负电荷的脂质体会迅速从循环中清除。为了克服这些问题，我们开发了高度安全有效的中性脂基纳米脂质体，在全身（静脉）给药后提供强大的肿瘤基因沉默。该输送系统在多种动物原位人类肿瘤模型中显示出显著的抗肿瘤效果。在这里，我们简要概述了这种和其他基于脂质的方法在不同肿瘤模型中用于癌症治疗的临床前应用，以及作为sirna纳米疗法在人类癌症中的潜在应用。
Small interfering RNAs (siRNA) have recently emerged as a new class of therapeutics with a great potential to revolutionize the treatment of cancer and other diseases. A specifically designed siRNA binds and induces post-transcriptional silencing of target genes (mRNA). Clinical applications of siRNA-based therapeutics have been limited by their rapid degradation, poor cellular uptake, and rapid renal clearance following systemic administration. A variety of synthetic and natural nanoparticles composed of lipids, polymers, and metals have been developed for siRNA delivery, with different efficacy and safety profiles. Liposomal nanoparticles have proven effective in delivering siRNA into tumor tissues by improving stability and bioavailability. While providing high transfection efficiency and a capacity to form complexes with negatively charged siRNA, cationic lipids/liposomes are highly toxic. Negatively charged liposomes, on the other hand, are rapidly cleared from circulation. To overcome these problems we developed highly safe and effective neutral lipid-based nanoliposomes that provide robust gene silencing in tumors following systemic (intravenous) administration. This delivery system demonstrated remarkable antitumor efficacy in various orthotopic human cancer models in animals. Here, we briefly overview this and other lipid-based approaches with preclinical applications in different tumor models for cancer therapy and potential applications as siRNA-nanotherapeutics in human cancers.