Lactate-driving Pt nanoflower with positive chemotaxis for deep intratumoral penetration. (August 2022)

• Record Type: Journal Article
• Authors: Zhang, Zhentao; Zhong, Haiqing; Zhou, Yi; Ke, Peng; Dai, Qi; Lu, Yiying; Zhong, Xincheng; Yang, Qiyao; Xia, Yiyi; Bao, Xiaoyan; Wu, Linjie; Han, Min; Gao, Jianqing
• Is Part Of: Nano today. Volume 45(2022)
• Publication Date: 2022-08
• Subjects: Lactate -- Positive chemotaxis -- Deep intratumoral penetration -- Hypoxic relief -- Radiosensitization; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2022.101542
• Languages: English
• ISSNs: 1748-0132

Abstract

Abstract: The deep penetration in response to specific intratumoral conditions holds considerable potential in achieving a more effective therapy. Lactate is mainly produced by exuberant-metabolism tumor cells growing in the deep center of solid tumor, which would form the characteristic of higher-level lactate deep inside tumor in distance with blood vessels. Herein, inspired by the in vitro directional chemotaxis of enzyme-powered nanomotor driven by substrate gradient, a novel lactate oxidase (LOX)-powered Pt Nanoflowers (Pt NFs) was developed to achieve deep intratumoral penetration triggered by the lactate-driving positive chemotaxis that was confirmed both in vitro and in vivo for the first time. Besides, LOX-powered Pt NFs with self-oxygenation could achieve a more thorough effect on hypoxic relief via the cascading catalysis: (1) the orthotopic extra H2 O2 production from lactate catalyzed by LOX, and (2) the effective conversion of both extra-supplement and endogenous H2 O2 into O2 catalyzed by Pt NFs, further overcoming the hypoxia-induced radioresistance. Meanwhile, the X-ray radiation deposited inside Pt NFs could improve low-dose radiotherapy effect with increasing ROS level and enhancing nuclear DNA damage. Collectively, this work would provide a blueprint for developing substrate gradient-driving "smart" delivery systems and radiosensitization strategy. Graphical Abstract: ga1 Highlights: An original lactate oxidase-modified device was utilized to observe and verify the lactate-driving positive chemotaxis. This work uncovered a novel enzyme-powered nanomotor driven by intratumoral lactate. This work demonstrated a breakthrough in the development of substrate gradient-driving systems for deep tumor curative.