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

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.

[1]  Samuel Achilefu,et al.  In vivo targeted deep-tissue photodynamic therapy based on near-infrared light triggered upconversion nanoconstruct. , 2013, ACS nano.

[2]  Patrick Couvreur,et al.  Stimuli-responsive nanocarriers for drug delivery. , 2013, Nature materials.

[3]  Bing Xu,et al.  Imaging enzyme-triggered self-assembly of small molecules inside live cells , 2012, Nature Communications.

[4]  W. Mark Saltzman,et al.  A holistic approach to targeting disease with polymeric nanoparticles , 2015, Nature Reviews Drug Discovery.

[5]  I. Hamachi,et al.  Ligand-directed tosyl chemistry for protein labeling in vivo. , 2009, Nature chemical biology.

[6]  Zhe Wang,et al.  Photosensitizer Loaded Nano-Graphene for Multimodality Imaging Guided Tumor Photodynamic Therapy , 2014, Theranostics.

[7]  Markus Grammel,et al.  Chemical reporters for biological discovery. , 2013, Nature chemical biology.

[8]  Q. Mei,et al.  Cellular Uptake and Antitumor Activity of DOX-hyd-PEG-FA Nanoparticles , 2014, PloS one.

[9]  M. Wang,et al.  Multifunctional Nano-Bioprobes Based on Rattle-Structured Upconverting Luminescent Nanoparticles. , 2015, Angewandte Chemie.

[10]  Linfeng Zheng,et al.  Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for in vivo tumor MR imaging. , 2013, Biomaterials.

[11]  Chris Jun Hui Ho,et al.  Multifunctional Photosensitizer-Based Contrast Agents for Photoacoustic Imaging , 2014, Scientific Reports.

[12]  Stefan Andersson-Engels,et al.  Upconverting nanoparticles for pre‐clinical diffuse optical imaging, microscopy and sensing: Current trends and future challenges , 2013 .

[13]  Zhen Cheng,et al.  In vitro and in vivo uncaging and bioluminescence imaging by using photocaged upconversion nanoparticles. , 2012, Angewandte Chemie.

[14]  Ick Chan Kwon,et al.  In vivo targeted delivery of nanoparticles for theranosis. , 2011, Accounts of chemical research.

[15]  Z. Chen,et al.  Sensitive and selective detection of glutathione based on resonance light scattering using sensitive gold nanoparticles as colorimetric probes. , 2012, The Analyst.

[16]  Grigory Tikhomirov,et al.  Bioorthogonal Cyclization-Mediated In Situ Self-Assembly of Small Molecule Probes for Imaging Caspase Activity in vivo , 2014, Nature chemistry.

[17]  H. Atwater,et al.  Plasmonics for improved photovoltaic devices. , 2010, Nature materials.

[18]  Dongmei Yang,et al.  Current advances in lanthanide ion (Ln(3+))-based upconversion nanomaterials for drug delivery. , 2015, Chemical Society reviews.

[19]  Carolyn R. Bertozzi,et al.  Chemical remodelling of cell surfaces in living animals , 2004, Nature.

[20]  A. Scorilas,et al.  Cathepsin B and cathepsin D expression in the progression of colorectal adenoma to carcinoma. , 2004, Cancer letters.

[21]  Hui Guo,et al.  Mesoporous-silica-coated up-conversion fluorescent nanoparticles for photodynamic therapy. , 2009, Small.

[22]  Xiaoman Zhang,et al.  A core-shell-shell nanoplatform upconverting near-infrared light at 808 nm for luminescence imaging and photodynamic therapy of cancer , 2015, Scientific Reports.

[23]  Jianghong Rao,et al.  A biocompatible condensation reaction for controlled assembly of nanostructures in live cells , 2010, Nature chemistry.

[24]  Wei Fan,et al.  Engineering the Upconversion Nanoparticle Excitation Wavelength: Cascade Sensitization of Tri‐doped Upconversion Colloidal Nanoparticles at 800 nm , 2013 .

[25]  Kai Yang,et al.  Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy. , 2012, Biomaterials.

[26]  C. Bertozzi,et al.  In Vivo Imaging of Membrane-Associated Glycans in Developing Zebrafish , 2008, Science.

[27]  Zhuang Liu,et al.  Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy. , 2011, Biomaterials.

[28]  Lihong V. Wang,et al.  Photoacoustic Tomography: In Vivo Imaging from Organelles to Organs , 2012, Science.

[29]  Joseph M. DeSimone,et al.  Strategies in the design of nanoparticles for therapeutic applications , 2010, Nature Reviews Drug Discovery.

[30]  N. Thakor,et al.  Rare-Earth Doped Particles as Dual-Modality Contrast Agent for Minimally-Invasive Luminescence and Dual-Wavelength Photoacoustic Imaging , 2014, Scientific Reports.

[31]  Sanjiv S. Gambhir,et al.  Activatable oligomerizable imaging agents for photoacoustic imaging of furin-like activity in living subjects. , 2013, Journal of the American Chemical Society.

[32]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

[33]  Chad A. Mirkin,et al.  Drivers of biodiagnostic development , 2009, Nature.

[34]  Yuliang Zhao,et al.  Elimination of Photon Quenching by a Transition Layer to Fabricate a Quenching‐Shield Sandwich Structure for 800 nm Excited Upconversion Luminescence of Nd3+‐Sensitized Nanoparticles , 2014, Advanced materials.

[35]  Muthu Kumara Gnanasammandhan,et al.  In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers , 2012, Nature Medicine.

[36]  Zhuang Liu,et al.  Imaging‐Guided pH‐Sensitive Photodynamic Therapy Using Charge Reversible Upconversion Nanoparticles under Near‐Infrared Light , 2013 .

[37]  D. Brömme,et al.  Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments in inhibitor design. , 2002, Chemical reviews.

[38]  Hakho Lee,et al.  Bioorthogonal chemistry amplifies nanoparticle binding and enhances the sensitivity of cell detection. , 2010, Nature nanotechnology.

[39]  Gang Zheng,et al.  Activatable photosensitizers for imaging and therapy. , 2010, Chemical reviews.

[40]  Wei Feng,et al.  Recent advances in the optimization and functionalization of upconversion nanomaterials for in vivo bioapplications , 2013 .

[41]  J. Chin,et al.  Cellular incorporation of unnatural amino acids and bioorthogonal labeling of proteins. , 2014, Chemical reviews.

[42]  Jinho Park,et al.  Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy , 2012, Theranostics.

[43]  Leilei Yin,et al.  Biomimetic surface engineering of lanthanide-doped upconversion nanoparticles as versatile bioprobes. , 2012, Angewandte Chemie.

[44]  Sanjiv S Gambhir,et al.  Nanooncology: The future of cancer diagnosis and therapy , 2013, CA: a cancer journal for clinicians.

[45]  Zhuang Liu,et al.  Near-infrared light induced in vivo photodynamic therapy of cancer based on upconversion nanoparticles. , 2011, Biomaterials.

[46]  Guangxia Shen,et al.  Light‐Triggered Theranostics Based on Photosensitizer‐Conjugated Carbon Dots for Simultaneous Enhanced‐Fluorescence Imaging and Photodynamic Therapy , 2012, Advanced materials.

[47]  Jan C. Hummelen,et al.  Broadband dye-sensitized upconversion of near-infrared light , 2012, Nature Photonics.

[48]  Fan Zhang,et al.  Single-band upconversion nanoprobes for multiplexed simultaneous in situ molecular mapping of cancer biomarkers , 2015, Nature Communications.

[49]  Qiang Sun,et al.  Mechanistic investigation of photon upconversion in Nd(3+)-sensitized core-shell nanoparticles. , 2013, Journal of the American Chemical Society.

[50]  Tymish Y. Ohulchanskyy,et al.  Photodynamic therapy by in situ nonlinear photon conversion , 2014, Nature Photonics.

[51]  Jie Shen,et al.  Stem Cell Labeling using Polyethylenimine Conjugated (α-NaYbF4:Tm3+)/CaF2 Upconversion Nanoparticles , 2013, Theranostics.

[52]  Wei Huang,et al.  Temporal full-colour tuning through non-steady-state upconversion. , 2015, Nature nanotechnology.

[53]  Andrew Tsourkas,et al.  ICP-MS analysis of lanthanide-doped nanoparticles as a non-radiative, multiplex approach to quantify biodistribution and blood clearance. , 2012, Biomaterials.

[54]  Chulhong Kim,et al.  Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. , 2011, Nature materials.

[55]  陈风,et al.  A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy , 2013 .

[56]  Liming Nie,et al.  Structural and functional photoacoustic molecular tomography aided by emerging contrast agents. , 2014, Chemical Society reviews.

[57]  Samir Mitragotri,et al.  Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies , 2014, Nature Reviews Drug Discovery.

[58]  Rein V Ulijn,et al.  Enzyme-assisted self-assembly under thermodynamic control. , 2009, Nature nanotechnology.

[59]  Jun Lin,et al.  Current Advances in Lanthanide Ion (Ln3+)-Based Upconversion Nanomaterials for Drug Delivery , 2015 .