A yolk-like multifunctional platform for multimodal imaging and synergistic therapy triggered by a single near-infrared light.

To integrate photodynamic therapy (PDT) with photothermal therapy (PTT) and chemotherapy for enhanced antitumor efficiency, we developed a mild and rational route to synthesize novel multifunctional GdOF:Ln@SiO2 (Ln = 10%Yb/1%Er/4%Mn) mesoporous capsules using strong up-conversion luminescent (UCL) GdOF:Ln as cores and mesoporous silica layer as shells, followed by modification with varied functional groups onto the framework. It was found that due to the codoped Yb/Er/Mn in GdOF, the markedly enhanced red emission can efficiently transfer energy to the conjugated PDT agent (ZnPc) which produces high singlet oxygen, and the incorporated carbon dots outside the shell can generate obvious thermal effect under 980 nm laser irradiation and also prevent the premature leaking of ZnPc. Simultaneously, the as-produced thermal effect can obviously enhance the doxorubicin (DOX) release, which greatly improves the chemotherapy, resulting in a synergistic therapeutic effect. The system exhibits drastically enhanced therapeutic efficiency against tumor growth, as demonstrated both in vitro and in vivo. Especially, the doped rare earth ions in the host endow the material with excellent UCL imaging, magnetic resonance imaging (MRI), and computed tomography (CT) imaging properties, thus realizing the target of multimodal imaging guided multiple therapies.

[1]  Peiyi Wu,et al.  Carbon nanodots featuring efficient FRET for two-photon photodynamic cancer therapy with a low fs laser power density. , 2014, Biomaterials.

[2]  Bin Liu,et al.  Conjugated-polyelectrolyte-based polyprodrug: targeted and image-guided photodynamic and chemotherapy with on-demand drug release upon irradiation with a single light source. , 2014, Angewandte Chemie.

[3]  B. Fei,et al.  Simultaneous Realization of Phase/Size Manipulation, Upconversion Luminescence Enhancement, and Blood Vessel Imaging in Multifunctional Nanoprobes Through Transition Metal Mn2+ Doping , 2014 .

[4]  Mingying Yang,et al.  Stem Cells Loaded with Nanoparticles as a Drug Carrier for In Vivo Breast Cancer Therapy , 2014, Advanced materials.

[5]  Jun Gao,et al.  A fullerene-based multi-functional nanoplatform for cancer theranostic applications. , 2014, Biomaterials.

[6]  Xiaoyuan Chen,et al.  Tumor Vasculature Targeted Photodynamic Therapy for Enhanced Delivery of Nanoparticles , 2014, ACS nano.

[7]  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.

[8]  Jianlin Shi,et al.  Hollow‐Structured Mesoporous Materials: Chemical Synthesis, Functionalization and Applications , 2014, Advanced materials.

[9]  Wenpei Fan,et al.  Real-time in vivo quantitative monitoring of drug release by dual-mode magnetic resonance and upconverted luminescence imaging. , 2014, Angewandte Chemie.

[10]  D. Shen,et al.  An upconversion nanoparticle--Zinc phthalocyanine based nanophotosensitizer for photodynamic therapy. , 2014, Biomaterials.

[11]  Chun-Hua Yan,et al.  Reversible near-infrared light directed reflection in a self-organized helical superstructure loaded with upconversion nanoparticles. , 2014, Journal of the American Chemical Society.

[12]  Jianhua Hao,et al.  Dual-modal upconversion fluorescent/X-ray imaging using ligand-free hexagonal phase NaLuF4:Gd/Yb/Er nanorods for blood vessel visualization. , 2014, Biomaterials.

[13]  Jun Lin,et al.  Recent progress in rare earth micro/nanocrystals: soft chemical synthesis, luminescent properties, and biomedical applications. , 2014, Chemical reviews.

[14]  Chun-Hua Yan,et al.  Paradigms and challenges for bioapplication of rare earth upconversion luminescent nanoparticles: small size and tunable emission/excitation spectra. , 2014, Accounts of chemical research.

[15]  Jun Lin,et al.  In vivo multimodality imaging and cancer therapy by near-infrared light-triggered trans-platinum pro-drug-conjugated upconverison nanoparticles. , 2013, Journal of the American Chemical Society.

[16]  Yun Sun,et al.  Core-shell lanthanide upconversion nanophosphors as four-modal probes for tumor angiogenesis imaging. , 2013, ACS nano.

[17]  Yuliang Zhao,et al.  A new near infrared photosensitizing nanoplatform containing blue-emitting up-conversion nanoparticles and hypocrellin A for photodynamic therapy of cancer cells. , 2013, Nanoscale.

[18]  Jun Lin,et al.  Rapid, large-scale, morphology-controllable synthesis of YOF:Ln3+ (Ln = Tb, Eu, Tm, Dy, Ho, Sm) nano-/microstructures with multicolor-tunable emission properties. , 2013, Inorganic chemistry.

[19]  Wei Feng,et al.  Upconversion‐Nanophosphor‐Based Functional Nanocomposites , 2013, Advanced materials.

[20]  T. Pędziński,et al.  Synthesis, spectroscopic and structural studies on YOF, LaOF and GdOF nanocrystals doped with Eu3+, synthesized via stearic acid method , 2013 .

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

[22]  Ru‐Shi Liu,et al.  Neighboring-cation substitution tuning of photoluminescence by remote-controlled activator in phosphor lattice. , 2013, Journal of the American Chemical Society.

[23]  Liang Yan,et al.  Recent Advances in Design and Fabrication of Upconversion Nanoparticles and Their Safe Theranostic Applications , 2013, Advanced materials.

[24]  Huimao Zhang,et al.  Conjugation of NaGdF4 upconverting nanoparticles on silica nanospheres as contrast agents for multi-modality imaging. , 2013, Biomaterials.

[25]  Rujia Zou,et al.  Sub-10 nm Fe3O4@Cu(2-x)S core-shell nanoparticles for dual-modal imaging and photothermal therapy. , 2013, Journal of the American Chemical Society.

[26]  Omar K. Yaghi,et al.  Ultra-low doses of chirality sorted (6,5) carbon nanotubes for simultaneous tumor imaging and photothermal therapy. , 2013, ACS nano.

[27]  Dongmei Yang,et al.  Hollow structured upconversion luminescent NaYF₄:Yb³⁺, Er³⁺ nanospheres for cell imaging and targeted anti-cancer drug delivery. , 2013, Biomaterials.

[28]  Yongsheng Liu,et al.  Breakdown of crystallographic site symmetry in lanthanide-doped NaYF4 crystals. , 2013, Angewandte Chemie.

[29]  Christopher McRae,et al.  Upconversion luminescence with tunable lifetime in NaYF4:Yb,Er nanocrystals: role of nanocrystal size. , 2013, Nanoscale.

[30]  Jianhua Hao,et al.  PEG modified BaGdF₅:Yb/Er nanoprobes for multi-modal upconversion fluorescent, in vivo X-ray computed tomography and biomagnetic imaging. , 2012, Biomaterials.

[31]  Lina Zhao,et al.  Enhanced red emission from GdF3:Yb3+,Er3+ upconversion nanocrystals by Li+ doping and their application for bioimaging. , 2012, Chemistry.

[32]  J. Fraser Stoddart,et al.  Mesoporous Silica Nanoparticles in Biomedical Applications , 2012 .

[33]  Jun Lin,et al.  Functionalized mesoporous silica materials for controlled drug delivery. , 2012, Chemical Society reviews.

[34]  Zongxi Li,et al.  Mesoporous silica nanoparticles in biomedical applications. , 2012, Chemical Society reviews.

[35]  Gang Han,et al.  Controlled synthesis and single-particle imaging of bright, sub-10 nm lanthanide-doped upconverting nanocrystals. , 2012, ACS nano.

[36]  Mingdong Huang,et al.  Amine-functionalized lanthanide-doped KGdF4 nanocrystals as potential optical/magnetic multimodal bioprobes. , 2012, Journal of the American Chemical Society.

[37]  Zhuang Liu,et al.  Upconversion nanophosphors for small-animal imaging. , 2012, Chemical Society reviews.

[38]  Chao Wang,et al.  Single-band upconversion emission in lanthanide-doped KMnF3 nanocrystals. , 2011, Angewandte Chemie.

[39]  A. Speghini,et al.  NIR-to-visible and NIR-to-NIR upconversion in lanthanide doped nanocrystalline GdOF with trigonal structure , 2011 .

[40]  Kai Yang,et al.  Facile preparation of multifunctional upconversion nanoprobes for multimodal imaging and dual-targeted photothermal therapy. , 2011, Angewandte Chemie.

[41]  Jianhua Hao,et al.  Electric-induced enhancement and modulation of upconversion photoluminescence in epitaxial BaTiO3:Yb/Er thin films. , 2011, Angewandte Chemie.

[42]  Renfu Li,et al.  Time-resolved FRET biosensor based on amine-functionalized lanthanide-doped NaYF4 nanocrystals. , 2011, Angewandte Chemie.

[43]  V. Bermudez,et al.  Progress on Lanthanide-Based Organic—Inorganic Hybrid Phosphors , 2011 .

[44]  Zhiqiang Gao,et al.  Strong Red-Emitting near-Infrared-to-Visible Upconversion Fluorescent Nanoparticles , 2011 .

[45]  Helmut Schäfer,et al.  Upconverting nanoparticles. , 2011, Angewandte Chemie.

[46]  Yong Zhang,et al.  Small upconverting fluorescent nanoparticles for biomedical applications. , 2010, Small.

[47]  Omid C Farokhzad,et al.  pH-Responsive nanoparticles for drug delivery. , 2010, Molecular pharmaceutics.

[48]  Xueyuan Chen,et al.  Upconversion nanoparticles in biological labeling, imaging, and therapy. , 2010, The Analyst.

[49]  Feng Chen,et al.  Hollow/rattle-type mesoporous nanostructures by a structural difference-based selective etching strategy. , 2010, ACS nano.

[50]  H. Choi,et al.  In vivo near-infrared mediated tumor destruction by photothermal effect of carbon nanotubes. , 2009, ACS Nano.

[51]  Yongmin Chang,et al.  Paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced T1 MRI contrast agent: account for large longitudinal relaxivity, optimal particle diameter, and in vivo T1 MR images. , 2009, ACS nano.

[52]  F. V. van Veggel,et al.  Hard proof of the NaYF(4)/NaGdF(4) nanocrystal core/shell structure. , 2009, Journal of the American Chemical Society.

[53]  Yadong Li,et al.  Upconversion luminescence of monodisperse CaF2:Yb(3+)/Er(3+) nanocrystals. , 2009, Journal of the American Chemical Society.

[54]  Steve Smith,et al.  Highly Luminescent NIR-to-Visible Upconversion Thin Films and Monoliths Requiring No High-Temperature Treatment , 2009 .

[55]  K. Uvdal,et al.  Synthesis and Characterization of Tb3+-Doped Gd2O3 Nanocrystals : A Bifunctional Material with Combined Fluorescent Labeling and MRI Contrast Agent Properties , 2009 .

[56]  Taeghwan Hyeon,et al.  Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. , 2009, Chemical Society reviews.

[57]  Yong Zhang,et al.  Nanoparticles in photodynamic therapy: an emerging paradigm. , 2008, Advanced drug delivery reviews.

[58]  Juan L. Vivero-Escoto,et al.  Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. , 2008, Advanced drug delivery reviews.

[59]  Xiaohua Huang,et al.  Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. , 2008, Accounts of chemical research.

[60]  Xiaogang Liu,et al.  Upconversion multicolor fine-tuning: visible to near-infrared emission from lanthanide-doped NaYF4 nanoparticles. , 2008, Journal of the American Chemical Society.

[61]  Yong Zhang,et al.  Upconversion fluorescence imaging of cells and small animals using lanthanide doped nanocrystals. , 2008, Biomaterials.

[62]  Thomas Nann,et al.  A four-color colloidal multiplexing nanoparticle system. , 2008, ACS nano.

[63]  Lijin Tian,et al.  Controlled Synthesis , Formation Mechanism , and Great Enhancement of Red Upconversion Luminescence of NaYF 4 : Yb , 2008 .

[64]  M. H. Yeung,et al.  Formation of Gold and Silver Nanoparticle Arrays and Thin Shells on Mesostructured Silica Nanofibers , 2007 .

[65]  María Vallet-Regí,et al.  Mesoporous materials for drug delivery. , 2007, Angewandte Chemie.

[66]  Paras N Prasad,et al.  Organically modified silica nanoparticles co-encapsulating photosensitizing drug and aggregation-enhanced two-photon absorbing fluorescent dye aggregates for two-photon photodynamic therapy. , 2007, Journal of the American Chemical Society.

[67]  A. Salazar,et al.  Carboxylation treatment of multiwalled carbon nanotubes monitored by infrared and ultraviolet spectroscopies and scanning probe microscopy , 2007 .

[68]  Frank Caruso,et al.  Biofunctionalization of fluorescent rare-earth-doped lanthanum phosphate colloidal nanoparticles. , 2004, Angewandte Chemie.

[69]  Hong Zhang,et al.  Femtosecond Studies of Solvation and Intramolecular Configurational Dynamics of Fluorophores in Liquid Solution , 2004 .

[70]  Schrum,et al.  Monitoring electroosmotic flow by periodic photobleaching of a dilute, neutral fluorophore , 2000, Analytical chemistry.

[71]  W. Stöber,et al.  Controlled growth of monodisperse silica spheres in the micron size range , 1968 .