title: In vivo covalent cross-linking of photon-converted rare-earth nanostructures for tumour localization and theranostics.
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.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore, Singapore.
authors.forename: Xiangzhao
authors.initials: X
authors.lastname: Ai
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), 138667 Singapore, Singapore.
authors.forename: Chris Jun Hui
authors.initials: CJ
authors.lastname: Ho
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore, Singapore.
authors.forename: Junxin
authors.initials: J
authors.lastname: Aw
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), 138667 Singapore, Singapore.
authors.forename: Amalina Binte Ebrahim
authors.initials: AB
authors.lastname: Attia
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore, Singapore.
authors.forename: Jing
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of Chemistry, National University of Singapore, 117543 Singapore, Singapore.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, 361102 Xiamen, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Radiation Medicine and Protection, Soochow University, 215123 Suzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, National University of Singapore, 117543 Singapore, Singapore.|Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 117602 Singapore, Singapore.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Radiation Medicine and Protection, Soochow University, 215123 Suzhou, China.
authors.forename: Huabing
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Radiation Medicine and Protection, Soochow University, 215123 Suzhou, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, 361102 Xiamen, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore, Singapore.
authors.forename: Edwin K L
authors.initials: EK
authors.lastname: Yeow
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, 361102 Xiamen, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), 138667 Singapore, Singapore.
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore, Singapore.|Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 117602 Singapore, Singapore.
authors.forename: Bengang
authors.initials: B
authors.lastname: Xing
mesh_terms: D000818:Animals; D005260:Female; D019073:HT29 Cells; D006801:Humans; D008674:Metals, Rare Earth / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry*; D017785:Photons; D026082:Singlet Oxygen / Q000737:chemistry; D000068936:Theranostic Nanomedicine / Q000379:methods*
chemical_list: D008674:Metals, Rare Earth; D026082:Singlet Oxygen