Core-shell hybrid nanogels for integration of optical temperature-sensing, targeted tumor cell imaging, and combined chemo-photothermal treatment.

We report a class of core-shell structured hybrid nanogels to demonstrate the conception of integrating the functional building blocks into a single nanoparticle system for simultaneously optical temperature-sensing, cancer cell targeting, fluorescence imaging, and combined chemo-photothermal treatment. The hybrid nanogels were constructed by coating the Ag-Au bimetallic NP core with a thermo-responsive nonlinear poly(ethylene glycol) (PEG)-based hydrogel as shell, and semi-interpenetrating the targeting ligands of hyaluronic acid chains into the surface networks of gel shell. The Ag-Au NP core can emit strong visible fluorescence for imaging of mouse melanoma B16F10 cells. The reversible thermo-responsive volume phase transition of the nonlinear PEG-based gel shell cannot only modify the physicochemical environment of the Ag-Au NP core to manipulate the fluorescence intensity for sensing the environmental temperature change, but also provide a high loading capacity for a model anticancer drug temozolomide and offer a thermo-triggered drug release. The drug release can be induced by both the heat generated by external NIR irradiation and the temperature increase of local environmental media. The ability of the hybrid nanogels to combine the local specific chemotherapy with external NIR photothermal treatment significantly improves the therapeutic efficacy due to a synergistic effect.

[1]  Robert Wilson The use of gold nanoparticles in diagnostics and detection. , 2008, Chemical Society reviews.

[2]  J. Scaiano,et al.  Facile photochemical synthesis and characterization of highly fluorescent silver nanoparticles. , 2009, Journal of the American Chemical Society.

[3]  F. Szoka,et al.  Anticancer therapeutics: targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor. , 2008, Molecular pharmaceutics.

[4]  Weitai Wu,et al.  Tunable Photoluminescence of Ag Nanocrystals in Multiple-Sensitive Hybrid Microgels , 2009 .

[5]  L. Dai,et al.  Can silver nanoparticles be useful as potential biological labels? , 2008, Nanotechnology.

[6]  J. Biollaz,et al.  Determination of temozolomide in human plasma and urine by high-performance liquid chromatography after solid-phase extraction. , 1995, Journal of chromatography. B, Biomedical applications.

[7]  Robert Langer,et al.  Impact of nanotechnology on drug delivery. , 2009, ACS nano.

[8]  T. Ishiguchi,et al.  Combination of chemotherapy and mild hyperthermia enhances the anti-tumor effects of cisplatin and adriamycin in human bladder cancer T24 cells in vitro , 2010 .

[9]  Jean-François Lutz,et al.  Preparation of Ideal PEG Analogues with a Tunable Thermosensitivity by Controlled Radical Copolymerization of 2-(2-Methoxyethoxy)ethyl Methacrylate and Oligo(ethylene glycol) Methacrylate , 2006 .

[10]  J. Ying,et al.  Bifunctional Fe3O4–Ag Heterodimer Nanoparticles for Two‐Photon Fluorescence Imaging and Magnetic Manipulation , 2008 .

[11]  Barry Lai,et al.  A high-performance nanobio photocatalyst for targeted brain cancer therapy. , 2009, Nano letters.

[12]  Luis M Liz-Marzán,et al.  Au@pNIPAM colloids as molecular traps for surface-enhanced, spectroscopic, ultra-sensitive analysis. , 2009, Angewandte Chemie.

[13]  Srikanth Pilla,et al.  Gold nanoparticles with a monolayer of doxorubicin-conjugated amphiphilic block copolymer for tumor-targeted drug delivery. , 2009, Biomaterials.

[14]  Naomi J Halas,et al.  Nanoshell-enabled photothermal cancer therapy: impending clinical impact. , 2008, Accounts of chemical research.

[15]  Monty Liong,et al.  Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. , 2008, ACS nano.

[16]  S. Wise Nanocarriers as an emerging platform for cancer therapy , 2007 .

[17]  Travis L. Jennings,et al.  Enhancing the Toxicity of Cancer Chemotherapeutics with Gold Nanorod Hyperthermia , 2008 .

[18]  J. West,et al.  Immunotargeted nanoshells for integrated cancer imaging and therapy. , 2005, Nano letters.

[19]  Peter Eaton,et al.  Gold nanoparticles for the development of clinical diagnosis methods , 2008, Analytical and bioanalytical chemistry.

[20]  K. Sokolov,et al.  Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods. , 2007, Nano letters.

[21]  Thomas C. Chen,et al.  The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas. , 2007, Cancer research.

[22]  Matthias Karg,et al.  Encapsulation and Growth of Gold Nanoparticles in Thermoresponsive Microgels , 2008 .

[23]  Kyujung Kim,et al.  Multifunctional nanoparticles for photothermally controlled drug delivery and magnetic resonance imaging enhancement. , 2008, Small.

[24]  Elodie Boisselier,et al.  Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. , 2009, Chemical Society reviews.

[25]  G. Hahn,et al.  Thermochemotherapy: synergism between hyperthermia (42-43 degrees) and adriamycin (of bleomycin) in mammalian cell inactivation. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Xiaohua Huang,et al.  Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. , 2006, Journal of the American Chemical Society.

[27]  Jutaek Nam,et al.  pH-Induced aggregation of gold nanoparticles for photothermal cancer therapy. , 2009, Journal of the American Chemical Society.

[28]  Martin Hofmann,et al.  A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells , 1991, Cell.

[29]  Vincent M Rotello,et al.  Gold nanoparticles in delivery applications. , 2008, Advanced drug delivery reviews.

[30]  Probal Banerjee,et al.  Smart Core—Shell Hybrid Nanogels with Ag Nanoparticle Core for Cancer Cell Imaging and Gel Shell for pH-Regulated Drug Delivery , 2010 .

[31]  Vincent M Rotello,et al.  Photoregulated release of caged anticancer drugs from gold nanoparticles. , 2009, Journal of the American Chemical Society.

[32]  I. Stamenkovic,et al.  CD44 is the principal cell surface receptor for hyaluronate , 1990, Cell.

[33]  S. Wuister,et al.  Luminescence temperature antiquenching of water-soluble CdTe quantum dots: role of the solvent. , 2004, Journal of the American Chemical Society.

[34]  서진석,et al.  Multifunctional nanoparticles for photothermally controlled drug delivery and magnetic resonance imaging enhancement , 2008 .

[35]  S. Gal,et al.  Assembly-disassembly of DNAs and gold nanoparticles: a strategy of intervention based on oligonucleotides and restriction enzymes. , 2008, Analytical chemistry.

[36]  Jess P. Wilcoxon,et al.  Photoluminescence from nanosize gold clusters , 1998 .

[37]  J. Zhang,et al.  Biomedical Applications of Shape-Controlled Plasmonic Nanostructures: A Case Study of Hollow Gold Nanospheres for Photothermal Ablation Therapy of Cancer , 2010 .

[38]  Younan Xia,et al.  Gold nanocages covered by smart polymers for controlled release with near-infrared light , 2009, Nature materials.

[39]  Jeffrey I. Zink,et al.  Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery , 2010, BiOS.

[40]  D. P. O'Neal,et al.  Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. , 2004, Cancer letters.

[41]  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.

[42]  Eric Pridgen,et al.  Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles , 2008, Molecular pharmaceutics.

[43]  Baowei Fei,et al.  Highly efficient drug delivery with gold nanoparticle vectors for in vivo photodynamic therapy of cancer. , 2008, Journal of the American Chemical Society.

[44]  Ick Chan Kwon,et al.  New Generation of Multifunctional Nanoparticles for Cancer Imaging and Therapy , 2009 .

[45]  Akira Fujishima,et al.  Multicolour photochromism of TiO2 films loaded with silver nanoparticles , 2003, Nature materials.

[46]  Michael Vollmer,et al.  Optical properties of metal clusters , 1995 .

[47]  M. El-Sayed,et al.  Gold and silver nanoparticles in sensing and imaging: sensitivity of plasmon response to size, shape, and metal composition. , 2006, The journal of physical chemistry. B.

[48]  J. Lutz,et al.  About the Phase Transitions in Aqueous Solutions of Thermoresponsive Copolymers and Hydrogels Based on 2-(2-methoxyethoxy)ethyl Methacrylate and Oligo(ethylene glycol) Methacrylate , 2007 .

[49]  R. Stafford,et al.  Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Younan Xia,et al.  Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model. , 2009, Nano letters.

[51]  Xiaohua Huang,et al.  Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles. , 2006, Cancer letters.

[52]  V. Rotello,et al.  Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells. , 2009, Journal of the American Chemical Society.

[53]  Hui Zhang,et al.  Immuno gold nanocages with tailored optical properties for targeted photothermal destruction of cancer cells. , 2007, Nano letters.

[54]  D. Gillet,et al.  Design and synthesis of single-nanoparticle optical biosensors for imaging and characterization of single receptor molecules on single living cells. , 2007, Analytical chemistry.

[55]  Chengli Song,et al.  Thermographic assessment of tumor growth in mouse xenografts , 2007, International journal of cancer.

[56]  Probal Banerjee,et al.  In-situ immobilization of quantum dots in polysaccharide-based nanogels for integration of optical pH-sensing, tumor cell imaging, and drug delivery. , 2010, Biomaterials.

[57]  N A Peppas,et al.  Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). , 2001, Advanced drug delivery reviews.

[58]  Vladimir P. Torchilin,et al.  Polyethylene Glycol-Diacyllipid Micelles Demonstrate Increased Accumulation in Subcutaneous Tumors in Mice , 2002, Pharmaceutical Research.

[59]  J. Storhoff,et al.  Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. , 1997, Science.

[60]  H. Too,et al.  Dissolution-recrystallization mechanism for the conversion of silver nanospheres to triangular nanoplates. , 2007, Journal of colloid and interface science.

[61]  Tong Cai,et al.  Oligo(ethylene glycol)-based thermoresponsive core-shell microgels. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[62]  Kyung-Hwa Yoo,et al.  Multifunctional nanoparticles for combined doxorubicin and photothermal treatments. , 2009, ACS nano.

[63]  Ralph Weissleder,et al.  Multifunctional magnetic nanoparticles for targeted imaging and therapy. , 2008, Advanced drug delivery reviews.

[64]  C. Xie,et al.  Nonbleaching fluorescence of gold nanoparticles and its applications in cancer cell imaging. , 2008, Analytical chemistry.

[65]  Younan Xia,et al.  A Comparative Study of Galvanic Replacement Reactions Involving Ag Nanocubes and AuCl2− or AuCl4− , 2008, Advanced materials.

[66]  J. West,et al.  Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. , 2007, Nano letters.

[67]  F. Szoka,et al.  Liposome-encapsulated doxorubicin targeted to CD44: a strategy to kill CD44-overexpressing tumor cells. , 2001, Cancer research.

[68]  D. Panagiotakos,et al.  Increased temperature of malignant urinary bladder tumors in vivo: the application of a new method based on a catheter technique. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[69]  J. Webster Encyclopedia of Medical Devices and Instrumentation , 1988 .

[70]  Warren C W Chan,et al.  Nanoparticle-mediated cellular response is size-dependent. , 2008, Nature nanotechnology.

[71]  Philip S Low,et al.  In vitro and in vivo two-photon luminescence imaging of single gold nanorods. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[72]  Byung-Soo Kim,et al.  Hyaluronic acid-quantum dot conjugates for in vivo lymphatic vessel imaging. , 2009, ACS nano.

[73]  V. Torchilin,et al.  Micellar Nanocarriers: Pharmaceutical Perspectives , 2006, Pharmaceutical Research.

[74]  I. Tannock,et al.  Treatment of cancer with radiation and drugs. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[75]  E. Zubarev,et al.  Paclitaxel-functionalized gold nanoparticles. , 2007, Journal of the American Chemical Society.