香港中文大学唐本忠团队报道了发光双金属纳米颗粒在肝窦中的快速生物转化。相关研究成果发表在2022年11月3日出版的《美国化学会杂志》。

肝隔离症主要由单核吞噬细胞系统（MPS）细胞的吞噬作用产生，是纳米粒子递送的长期障碍，严重降低疾病靶向能力，导致纳米毒性，并抑制临床转化。

为了避免长期的肝脏隔离，研究人员精心设计了发光的金-银双金属纳米颗粒，它可以被富含谷胱甘肽和氧气的肝脏正弦微环境快速转化，这与由于生物转化速度慢而被Kupffer细胞快速隔离的单金属金纳米颗粒有很大不同。

研究发现，谷胱甘肽和氧与活性银原子协同反应诱导的快速正弦生物转化，可以帮助双金属纳米颗粒避免MPS吞噬，促进肝脏快速释放，延长血液循环，增强肾脏清除率，增加疾病靶向性。随着窦状体内的快速生物转化，肝脏隔离可以成为纳米药物的一种有益储存机制，并最大限度地提高靶向性。

附：英文原文

Title: Rapid Biotransformation of Luminescent Bimetallic Nanoparticles in Hepatic Sinusoids

Author: Yue Tan, Wei Cai, Caiming Luo, Jiahao Tang, Ryan T. K. Kwok, Jacky W. Y. Lam, Jianwei Sun, Jinbin Liu, Ben Zhong Tang

Issue&Volume: November 3, 2022

Abstract: Liver sequestration, mainly resulting from the phagocytosis of mononuclear phagocyte system (MPS) cells, is a long-standing barrier in nanoparticle delivery, which severely decreases the disease-targeting ability, leads to nanotoxicity, and inhibits clinical translation. To avoid long-term liver sequestration, we elaborately designed luminescent gold–silver bimetallic nanoparticles that could be rapidly transformed by the hepatic sinusoidal microenvironment rich in glutathione and oxygen, significantly different from monometallic gold nanoparticles that were rapidly sequestrated by Kupffer cells due to the much slower biotransformation. We found that the rapid sinusoidal biotransformation induced by the synergistic reactions of glutathione and oxygen with the reactive silver atoms could help bimetallic nanoparticles to avoid MPS phagocytosis, promote fast release from the liver, prolong blood circulation, enhance renal clearance, and increase disease targeting. With the fast biotransformation in sinusoids, liver sequestration could be turned into a beneficial storage mechanism for nanomedicines to maximize targeting.

DOI: 10.1021/jacs.2c07657

Source: https://pubs.acs.org/doi/10.1021/jacs.2c07657