In vivo covalent cross-linking of photon-converted rare-earth nanostructures for tumour localization and theranostics

Nature Communications
Xiangzhao AiBengang Xing

Abstract

The development of precision nanomedicines to direct nanostructure-based reagents into tumour-targeted areas remains a critical challenge in clinics. Chemical reaction-mediated localization in response to tumour environmental perturbations offers promising opportunities for rational design of effective nano-theranostics. Here, we present a unique microenvironment-sensitive strategy for localization of peptide-premodified upconversion nanocrystals (UCNs) within tumour areas. Upon tumour-specific cathepsin protease reactions, the cleavage of peptides induces covalent cross-linking between the exposed cysteine and 2-cyanobenzothiazole on neighbouring particles, thus triggering the accumulation of UCNs into tumour site. Such enzyme-triggered cross-linking of UCNs leads to enhanced upconversion emission upon 808 nm laser irradiation, and in turn amplifies the singlet oxygen generation from the photosensitizers attached on UCNs. Importantly, this design enables remarkable tumour inhibition through either intratumoral UCNs injection or intravenous injection of nanoparticles modified with the targeting ligand. Our strategy may provide a multimodality solution for effective molecular sensing and site-specific tumour treatment.

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Citations

Feb 9, 2017·ACS Applied Materials & Interfaces·Dan YangPiaoping Yang
Feb 25, 2017·ACS Applied Materials & Interfaces·Xueke SunHongwei Song
May 17, 2017·Advanced Healthcare Materials·Yunlu DaiFrank Caruso
Apr 17, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Vahid MirshafieeTian Xia
Mar 9, 2017·Nanoscale·Yanmei YangBengang Xing
Oct 7, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Ming HuBengang Xing
Jul 18, 2017·ACS Applied Materials & Interfaces·Honglin JinZhenwei Zou
May 4, 2018·Therapeutic Delivery·Gaurav ParekhStefano Leporatti
Jul 4, 2018·Advanced Healthcare Materials·Ji QiBen Zhong Tang
Jul 13, 2018·Advanced Healthcare Materials·Tiancong MaMingyuan Gao
Aug 31, 2016·Science Advances·Congqing ZhuHaiping Xia

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Methods Mentioned

BETA
transmission
dynamic light scattering
imaging technique
light scattering
imaging techniques
ELISA
xenograft
fluorescence imaging
Fluorescence
confocal microscopy

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