In Vivo Behavior of Ultrasmall Spherical Nucleic Acids.
In Vivo Behavior of Ultrasmall Spherical Nucleic Acids.
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DOI：
10.1002/smll.202300097
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发表时间：
2023-03
期刊：
影响因子：
13.3
通讯作者：
Cassandra E. Callmann;Matthew K Vasher;Anindita Das;Caroline D. Kusmierz;C. Mirkin
中科院分区：
文献类型：
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作者：
Cassandra E. Callmann;Matthew K Vasher;Anindita Das;Caroline D. Kusmierz;C. Mirkin
球形核酸（SNA）的生物学特性在很大程度上独立于纳米颗粒核心的身份，但受寡核苷酸表面密度的影响。此外，有效载荷到载体（即，SNA的DNA与纳米颗粒的质量比与核尺寸成反比。虽然已经开发了具有许多核类型和尺寸的SNA，但是SNA行为的所有体内分析都限于直径>10 nm的核。然而，“超小”纳米颗粒构建体（直径<10 nm）可以表现出增加的有效载荷与载体比率、减少的肝脏积累、肾清除和增强的肿瘤浸润。因此，我们假设具有超小核的SNA表现出SNA样性质，但体内行为类似于传统的超小纳米颗粒。为了研究，我们比较了具有1.4 nm Au 102纳米团簇核心的SNA（AuNC-SNA）和具有10 nm金纳米颗粒核心的SNA（AuNP-SNA）的行为。值得注意的是，AuNC-SNA具有SNA样性质（例如，高细胞摄取，低细胞毒性），但显示出不同的体内行为。当静脉注射到小鼠中时，AuNC-SNA显示出比AuNP-SNA延长的血液循环、更低的肝脏积累和更高的肿瘤积累。因此，SNA样性质持续在亚10 nm的长度尺度和寡核苷酸的安排和表面密度是负责SNA的生物学特性。这项工作的影响，新的纳米载体的治疗应用的设计。
The biological properties of spherical nucleic acids (SNAs) are largely independent of nanoparticle core identity but significantly affected by oligonucleotide surface density. Additionally, the payload-to-carrier (i.e., DNA-to-nanoparticle) mass ratio of SNAs is inversely proportional to core size. While SNAs with many core types and sizes have been developed, all in vivo analyses of SNA behavior have been limited to cores >10 nm in diameter. However, "ultrasmall" nanoparticle constructs (<10 nm diameter) can exhibit increased payload-to-carrier ratios, reduced liver accumulation, renal clearance, and enhanced tumor infiltration. Therefore, we hypothesized that SNAs with ultrasmall cores exhibit SNA-like properties, but with in vivo behavior akin to traditional ultrasmall nanoparticles. To investigate, we compared the behavior of SNAs with 1.4-nm Au102 nanocluster cores (AuNC-SNAs) and SNAs with 10-nm gold nanoparticle cores (AuNP-SNAs). Significantly, AuNC-SNAs possess SNA-like properties (e.g., high cellular uptake, low cytotoxicity) but show distinct in vivo behavior. When intravenously injected in mice, AuNC-SNAs display prolonged blood circulation, lower liver accumulation, and higher tumor accumulation than AuNP-SNAs. Thus, SNA-like properties persist at the sub-10-nm length scale and oligonucleotide arrangement and surface density are responsible for the biological properties of SNAs. This work has implications for the design of new nanocarriers for therapeutic applications.