Poly(Acrylic Acid) Modification of Nd3+‐Sensitized Upconversion Nanophosphors for Highly Efficient UCL Imaging and pH‐Responsive Drug Delivery

In this work, a simple method is demonstrated for the synthesis of multifunctional core–shell nanoparticles NaYF4:Yb,Er@NaYF4:Yb@NaNdF4:Yb@NaYF4:Yb@PAA (labeled as Er@Y@Nd@Y@PAA or UCNP@PAA), which contain a highly effective 808‐nm‐to‐visible UCNP core and a thin shell of poly(acrylic acid) (PAA) to achieve upconversion bioimaging and pH‐sensitive anticancer chemotherapy simultaneously. The core–shell Nd3+‐sensitized UCNPs are optimized by varying the shell number, core size, and host lattices. The final optimized Er@Y@Nd@Y nanoparticle composition shows a significantly improved upconversion luminescence intensity, that is, 12.8 times higher than Er@Y@Nd nanoparticles. After coating the nanocomposites with a thin layer of PAA, the resulting UCNP@PAA nanocomposite perform well as a pH‐responsive nanocarrier and show clear advantages over UCNP@mSiO2, which are evidenced by in vitro/in vivo experiments. Histological analysis also reveals that no pathological changes or inflammatory responses occur in the heart, lungs, kidneys, liver, and spleen. In summary, this study presents a major step forward towards a new therapeutic and diagnostic treatment of tumors by using 808‐nm excited UCNPs to replace the traditional 980‐nm excitation.

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

[2]  Wei Zheng,et al.  Lanthanide-doped upconversion nano-bioprobes: electronic structures, optical properties, and biodetection. , 2015, Chemical Society reviews.

[3]  Shanshan Huang,et al.  Multifunctional NaYF4:Yb, Er@mSiO2@Fe3O4-PEG nanoparticles for UCL/MR bioimaging and magnetically targeted drug delivery. , 2015, Nanoscale.

[4]  Jin Chang,et al.  Smart pH-responsive upconversion nanoparticles for enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy. , 2015, Chemical communications.

[5]  Yixiao Zhang,et al.  An upconversion nanoparticle with orthogonal emissions using dual NIR excitations for controlled two-way photoswitching. , 2014, Angewandte Chemie.

[6]  Xiaoming Li,et al.  Epitaxial seeded growth of rare-earth nanocrystals with efficient 800 nm near-infrared to 1525 nm short-wavelength infrared downconversion photoluminescence for in vivo bioimaging. , 2014, Angewandte Chemie.

[7]  J. Gooding,et al.  Dual Bioresponsive Mesoporous Silica Nanocarrier as an “AND” Logic Gate for Targeted Drug Delivery Cancer Cells , 2014 .

[8]  N. J. Johnson,et al.  Lanthanide-based heteroepitaxial core-shell nanostructures: compressive versus tensile strain asymmetry. , 2014, ACS nano.

[9]  Has nanomedicine lived up to its promise? , 2014, Nanotechnology.

[10]  Jeffrey N. Anker,et al.  Multifunctional yolk-in-shell nanoparticles for pH-triggered drug release and imaging. , 2014, Small.

[11]  Yong Zhang,et al.  A paradigm shift in the excitation wavelength of upconversion nanoparticles. , 2014, Nanoscale.

[12]  Sami Koho,et al.  Photon upconversion sensitized nanoprobes for sensing and imaging of pH. , 2014, Nanoscale.

[13]  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.

[14]  Shanshan Huang,et al.  Upconversion‐Luminescent Core/Mesoporous‐Silica‐Shell‐Structured β‐NaYF4:Yb3+,Er3+@SiO2@mSiO2 Composite Nanospheres: Fabrication and Drug‐Storage/Release Properties , 2014 .

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

[16]  Yadong Li,et al.  Energy upconversion in lanthanide-doped core/porous-shell nanoparticles. , 2014, Inorganic chemistry.

[17]  P. Prasad,et al.  Upconversion Nanoparticles: Design, Nanochemistry, and Applications in Theranostics , 2014, Chemical reviews.

[18]  D. Sardar,et al.  Stokes emission in GdF₃:Nd³⁺ nanoparticles for bioimaging probes. , 2014, Nanoscale.

[19]  J. Gore,et al.  Synthesis of brightly PEGylated luminescent magnetic upconversion nanophosphors for deep tissue and dual MRI imaging. , 2014, Small.

[20]  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.

[21]  Jun Lin,et al.  Multifunctional upconversion mesoporous silica nanostructures for dual modal imaging and in vivo drug delivery. , 2013, Small.

[22]  Lei Zhou,et al.  Nd3+ Sensitized Up/Down Converting Dual-Mode Nanomaterials for Efficient In-vitro and In-vivo Bioimaging Excited at 800 nm , 2013, Scientific Reports.

[23]  Hai Zhu,et al.  Upconverting near-infrared light through energy management in core-shell-shell nanoparticles. , 2013, Angewandte Chemie.

[24]  Kemin Wang,et al.  Polyacrylic acid modified upconversion nanoparticles for simultaneous pH-triggered drug delivery and release imaging. , 2013, Journal of biomedical nanotechnology.

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

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

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

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

[29]  Ling-Dong Sun,et al.  Nd(3+)-sensitized upconversion nanophosphors: efficient in vivo bioimaging probes with minimized heating effect. , 2013, ACS nano.

[30]  Yongsheng Liu,et al.  Lanthanide-doped luminescent nanoprobes: controlled synthesis, optical spectroscopy, and bioapplications. , 2013, Chemical Society reviews.

[31]  Shuangxi Xing,et al.  Designed fabrication of unique eccentric mesoporous silica nanocluster-based core-shell nanostructures for pH-responsive drug delivery. , 2013, ACS applied materials & interfaces.

[32]  Huan Xu,et al.  Iron oxide @ polypyrrole nanoparticles as a multifunctional drug carrier for remotely controlled cancer therapy with synergistic antitumor effect. , 2013, ACS nano.

[33]  Qingfeng Xiao,et al.  Rattle-structured multifunctional nanotheranostics for synergetic chemo-/radiotherapy and simultaneous magnetic/luminescent dual-mode imaging. , 2013, Journal of the American Chemical Society.

[34]  Shuangxi Xing,et al.  Generalized approach to the synthesis of reversible concentric and eccentric polymer-coated nanostructures. , 2013, Small.

[35]  Z. Su,et al.  Multifunctional magnetic-fluorescent eccentric-(concentric-Fe₃O₄@SiO₂@polyacrylic acid core-shell nanocomposites for cell imaging and pH-responsive drug delivery. , 2013, Nanoscale.

[36]  Dongmei Yang,et al.  Poly(acrylic acid) modified lanthanide-doped GdVO4 hollow spheres for up-conversion cell imaging, MRI and pH-dependent drug release. , 2013, Nanoscale.

[37]  Jun Lin,et al.  A facile fabrication of upconversion luminescent and mesoporous core-shell structured β-NaYF4:Yb3+, Er3+@mSiO2 nanocomposite spheres for anti-cancer drug delivery and cell imaging. , 2013, Biomaterials science.

[38]  Jong-in Hahm.  Biomedical detection via macro- and nano-sensors fabricated with metallic and semiconducting oxides. , 2013, Journal of biomedical nanotechnology.

[39]  Sava Sakadžić,et al.  Dendritic upconverting nanoparticles enable in vivo multiphoton microscopy with low-power continuous wave sources , 2012, Proceedings of the National Academy of Sciences.

[40]  Wei Li,et al.  Direct imaging the upconversion nanocrystal core/shell structure at the subnanometer level: shell thickness dependence in upconverting optical properties. , 2012, Nano letters.

[41]  B. Tomanek,et al.  Cation Exchange: A Facile Method To Make NaYF4:Yb,Tm-NaGdF4 Core–Shell Nanoparticles with a Thin, Tunable, and Uniform Shell , 2012 .

[42]  Lianzhou Wang,et al.  Positive and Negative Lattice Shielding Effects Co‐existing in Gd (III) Ion Doped Bifunctional Upconversion Nanoprobes , 2011 .

[43]  Zhan Shi,et al.  Breakthrough in concentration quenching threshold of upconversion luminescence via spatial separation of the emitter doping area for bio-applications. , 2011, Chemical communications.

[44]  Shuk Han Cheng,et al.  Polymer-coated NaYF₄:Yb³⁺, Er³⁺ upconversion nanoparticles for charge-dependent cellular imaging. , 2011, ACS nano.

[45]  Zhengping Li,et al.  Surface modification of hydrophobic NaYF4:Yb,Er upconversion nanophosphors and their applications for immunoassay , 2011 .

[46]  Li Yuan,et al.  Preparation of pH-Responsive Mesoporous Silica Nanoparticles and Their Application in Controlled Drug Delivery , 2011 .

[47]  Yang Yang,et al.  Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors. , 2010, Biomaterials.

[48]  Yang Wei,et al.  Synthesis of Oil-Dispersible Hexagonal-Phase and Hexagonal-Shaped NaYF4:Yb,Er Nanoplates , 2006 .

[49]  Taeghwan Hyeon,et al.  Ultra-large-scale syntheses of monodisperse nanocrystals , 2004, Nature materials.