With the development of nanotechnology, various drug delivery systems including inorganic nanoparticles, liposomes, polymers, etc. have been developed over the past decade. Some of these nanoparticles are also forthcoming candidates for the successful delivery of small interfering RNA (siRNA) for targeted gene silencing. Upon its discovery, siRNA was perceived as a highly promising agent in the treatment of various diseases. However, it could not exhibit the expected clinical outcomes owing to the unfavorable challenges during delivery. One such challenge was identified as the lack of an effective carrier. Among the carriers, calcium phosphate (CaP) nanoparticles have attracted remarkable attention due to the superior biochemical properties and hold great promise for siRNA. It is well known that synthesis conditions influence the types of crystalline phases of CaPs as well as morphology. In this study, to address the influence of these parameters on the success of siRNA delivery, three different arginine (Arg) modified CaP nanoparticles having different chemical and morphological characteristics were synthesized as being the carriers of two specific siRNAs against survivin and cyclin B1. The functioning of CaP surfaces with Arg results in positive zeta potential on the surfaces. Functionalized nanoparticles have a higher loading capacity compared to unmodified particles, as they have a cationic surface that can be easily attached to negatively charged siRNAs. The gene silencing ability and the consequent in vitro antitumor activity of these CaP-Arg-siRNA complexes were investigated using A549 non-small-cell lung cancer cells. We found that high survivin and cyclin B1 expression is associated with worse survival in patients with lung cancer based on the Kaplan-Meier database. Considering the promoting role of survivin and cyclin B1 in cancer development and progression, CaP-Arg-siRNA mediated suppression of these genes resulted in a significant decrease in cell growth and induction of apoptosis. Our data suggest that all three CaP-Arg nanoparticles synthesized in this work can be used as safe and efficient nanocarriers for siRNA delivery, offering the opportunity to develop new therapeutic strategies for the treatment of lung cancer.

随着纳米技术的发展，在过去的十年中已经开发了包括无机纳米颗粒，脂质体，聚合物等在内的各种药物递送系统。这些纳米颗粒中的一些也即将成功地用于靶向基因沉默的小干扰RNA（siRNA）的交付。发现后，siRNA被认为是治疗各种疾病的极有前途的药物。然而，由于分娩过程中的不利挑战，它不能表现出预期的临床结果。此类挑战之一被确定为缺乏有效的载体。在载体中，磷酸钙（CaP）纳米颗粒因其优异的生化特性而引起了人们的极大关注，并为siRNA带来了广阔前景。众所周知，合成条件会影响CaPs结晶相的类型以及形态。在这项研究中，为了解决这些参数对siRNA传递成功的影响，合成了三种不同的精氨酸（Arg）修饰的CaP纳米颗粒，它们具有不同的化学和形态学特征，它们是两种针对survivin和cyclin B1的特异性siRNA的载体。CaP表面具有Arg的功能可在表面上产生正的Zeta电位。与未修饰的颗粒相比，官能化的纳米颗粒具有更高的负载能力，因为它们具有易于附着至带负电荷的siRNA的阳离子表面。基因沉默能力及其结果 为了解决这些参数对siRNA传递成功的影响，合成了三种具有不同化学和形态学特征的精氨酸（Arg）修饰的CaP纳米颗粒，它们是两种针对survivin和cyclin B1的特异性siRNA的载体。CaP表面具有Arg的功能可在表面上产生正的Zeta电位。与未修饰的颗粒相比，官能化的纳米颗粒具有更高的负载能力，因为它们具有易于附着至带负电荷的siRNA的阳离子表面。基因沉默能力及其结果 为了解决这些参数对siRNA传递成功的影响，合成了三种具有不同化学和形态学特征的精氨酸（Arg）修饰的CaP纳米颗粒，它们是两种针对survivin和cyclin B1的特异性siRNA的载体。CaP表面具有Arg的功能可在表面上产生正的Zeta电位。与未修饰的颗粒相比，功能化的纳米颗粒具有更高的负载能力，因为它们具有易于附着至带负电荷的siRNA的阳离子表面。基因沉默能力及其结果 CaP表面具有Arg的功能可在表面上产生正的Zeta电位。与未修饰的颗粒相比，官能化的纳米颗粒具有更高的负载能力，因为它们具有易于附着至带负电荷的siRNA的阳离子表面。基因沉默能力及其结果 CaP表面具有Arg的功能可在表面上产生正的Zeta电位。与未修饰的颗粒相比，官能化的纳米颗粒具有更高的负载能力，因为它们具有易于附着至带负电荷的siRNA的阳离子表面。基因沉默能力及其结果使用A549非小细胞肺癌细胞研究了这些CaP-Arg-siRNA复合物的体外抗肿瘤活性。我们发现，根据Kaplan-Meier数据库，survivin和cyclin B1的高表达与肺癌患者较差的生存率相关。考虑到存活蛋白和细胞周期蛋白B1在癌症发展和进展中的促进作用，CaP-Arg-siRNA介导的这些基因的抑制导致细胞生长和凋亡诱导的显着减少。我们的数据表明，在这项工作中合成的所有三个CaP-Arg纳米颗粒都可以用作siRNA输送的安全，有效的纳米载体，从而为开发治疗肺癌的新治疗策略提供了机会。