Macrophage-Encapsulated Bioorthogonal Nanozymes for Targeting Cancer Cells

被引：27

作者：

Das, Riddha ^{[1
]}

Hardie, Joseph ^{[1
]}

Joshi, Bishnu P. ^{[1
]}

Zhang, Xianzhi ^{[1
]}

Gupta, Aarohi ^{[1
]}

Luther, David C. ^{[1
]}

Fedeli, Stefano ^{[1
]}

Farkas, Michelle E. ^{[1
]}

Rotello, Vincent M. ^{[1
]}

机构：

[1] Univ Massachusetts, Dept Chem, Amherst, MA 01003 USA

来源：

JACS AU | 2022年 / 2卷 / 07期

关键词：

chemotherapy; gold nanoparticles; catalyst; cell-based delivery; bioorthogonal; tumor; STIMULI-RESPONSIVE NANOCARRIERS; GOLD NANOPARTICLES; DELIVERY; DRUG; CHEMISTRY; TUMORS; SIZE; 5-FLUOROURACIL; MECHANISMS; CATALYSIS;

D O I：

10.1021/jacsau.2c00247

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Macrophages migrate to tumor sites by following chemoattractant gradients secreted by tumor cells, providing a truly active targeting strategy for cancer therapy. However, macrophage-based delivery faces challenges of cargo loading, control of release, and effects of the payload on the macrophage vehicle. We present a strategy that employs bioorthogonal "nanozymes" featuring transition metal catalysts (TMCs) to provide intracellular "factories" for the conversion of prodyes and prodrugs into imaging agents and chemotherapeutics. These nanozymes solubilize and stabilize the TMCs by embedding them into self-assembled monolayer coating gold nanopartides. Nanozymes delivered into macrophages were intracellularly localized and retained activity even after prolonged (72 h) incubation. Significantly, nanozyme-loaded macrophages maintained their inherent migratory ability toward tumor cell chemoattractants, efficiently killing cancer cells in cocultures. This work establishes the potential of nanozyme-loaded macrophages for tumor site activation of prodrugs, providing readily tunable dosages and delivery rates while minimizing off-target toxicity of chemotherapeutics.

引用

页码：1679 / 1685

页数：7

共 71 条

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