National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, P. R. China.
Laboratory of Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University Chengdu, Sichuan, Chengdu, 610041, P. R. China.
Small. 2020 Mar;16(10):e1906538. doi: 10.1002/smll.201906538. Epub 2020 Feb 5.
Codelivery of diagnostic probes and therapeutic molecules often suffers from intrinsic complexity and premature leakage from or degradation of the nanocarrier. Inspired by the "Y" shape of indocyanine green (ICG), the dye is integrated in an amphiphilic lipopeptide (RNF). The hydrophilic segment is composed of arginine-rich dendritic peptides, while cyanine dyes are modified with two long carbon chains and employed as the hydrophobic moiety. They are linked through a disulfide linkage to improve the responsivity in the tumor microenvironment. After formulation with other lipopeptides at an optimized ratio, the theranostic system (RNS-2) forms lipid-based nanoparticles with slight positive zeta potential enabling efficient condensation of DNA. The RNS-2 displays glutathione responded gene release, activatable fluorescence recovery, and up to sevenfold higher in vitro transfection than Lipofectamine 2000. Compared with a Cy3 and Cy5 labeled fluorescence resonance energy transfer indicator for gene release, the "turn-on" indocyanine green analogs exhibit longer emission wavelength and better positive correlation with the dynamic processes of gene delivery. More importantly, the RNS-2 system enables efficient near infrared imaging guided gene transfer in tumor-bearing mice and thus provides more precise and accurate information on location of the cargo gene and synthesized carriers.
诊断探针和治疗分子的共递送常常受到内在复杂性以及纳米载体的过早泄漏或降解的影响。受吲哚菁绿（ICG）的“Y”形状的启发，染料被整合到两亲性脂肽（RNF）中。亲水性部分由富含精氨酸的树枝状肽组成，而菁染料用两条长碳链修饰并用作疏水性部分。它们通过二硫键连接以提高在肿瘤微环境中的响应性。在与其他脂肽以优化的比例进行配方后，治疗诊断系统（RNS-2）形成带轻微正 ζ 电位的基于脂质的纳米颗粒，能够有效地使 DNA 凝结。RNS-2 显示出谷胱甘肽响应性基因释放、可激活的荧光恢复，以及比 Lipofectamine 2000 高 7 倍的体外转染效率。与用于基因释放的 Cy3 和 Cy5 标记的荧光共振能量转移指示剂相比，“开启”的吲哚菁绿类似物具有更长的发射波长，并且与基因传递的动态过程具有更好的正相关性。更重要的是，RNS-2 系统能够在荷瘤小鼠中进行有效的近红外成像引导基因转移，从而提供有关货物基因和合成载体位置的更精确和准确的信息。
