Self-assembled plasmonic vesicles of SERS-encoded amphiphilic gold nanoparticles for cancer cell targeting and traceable intracellular drug delivery.

We report the development of bioconjugated plasmonic vesicles assembled from SERS-encoded amphiphilic gold nanoparticles for cancer-targeted drug delivery. This new type of plasmonic assemblies with a hollow cavity can play multifunctional roles as delivery carriers for anticancer drugs and SERS-active plasmonic imaging probes to specifically label targeted cancer cells and monitor intracellular drug delivery. We have shown that the pH-responsive disassembly of the plasmonic vesicle, stimulated by the hydrophobic-to-hydrophilic transition of the hydrophobic brushes in acidic intracellular compartments, allows for triggered intracellular drug release. Because self-assembled plasmonic vesicles exhibit significantly different plasmonic properties and greatly enhanced SERS intensity in comparison with single gold nanoparticles due to strong interparticle plasmonic coupling, disassembly of the vesicles in endocytic compartments leads to dramatic changes in scattering properties and SERS signals, which can serve as independent feedback mechanisms to signal cargo release from the vesicles. The unique structural and optical properties of the plasmonic vesicle have made it a promising platform for targeted combination therapy and theranostic applications by taking advantage of recent advances in gold nanostructure based in vivo bioimaging and photothermal therapy and their loading capacity for both hydrophilic (nucleic acids and proteins) and hydrophobic (small molecules) therapeutic agents.

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

[2]  Jesse V Jokerst,et al.  Molecular imaging with theranostic nanoparticles. , 2011, Accounts of chemical research.

[3]  Wolfgang Meier,et al.  Polymeric vesicles: from drug carriers to nanoreactors and artificial organelles. , 2011, Accounts of chemical research.

[4]  Chad A Mirkin,et al.  Nanostructures in biodiagnostics. , 2005, Chemical reviews.

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

[6]  George C Schatz,et al.  Dispersible gold nanorod dimers with sub-5 nm gaps as local amplifiers for surface-enhanced Raman scattering. , 2012, Nano letters.

[7]  Daejin Kim,et al.  Bioinspired colorimetric detection of calcium(II) ions in serum using calsequestrin-functionalized gold nanoparticles. , 2009, Angewandte Chemie.

[8]  Igor L. Medintz,et al.  Materials for fluorescence resonance energy transfer analysis: beyond traditional donor-acceptor combinations. , 2006, Angewandte Chemie.

[9]  Sarit S. Agasti,et al.  Recognition-Mediated Activation of Therapeutic Gold Nanoparticles Inside Living Cells , 2010, Nature chemistry.

[10]  Hongyu Chen,et al.  Measuring ensemble-averaged surface-enhanced Raman scattering in the hotspots of colloidal nanoparticle dimers and trimers. , 2010, Journal of the American Chemical Society.

[11]  M. Bruchez,et al.  Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots , 2003, Nature Biotechnology.

[12]  K. Kataoka,et al.  Glucose-responsive polymer bearing a novel phenylborate derivative as a glucose-sensing moiety operating at physiological pH conditions. , 2003, Biomacromolecules.

[13]  S. Bon,et al.  Polymer vesicles with a colloidal armor of nanoparticles. , 2011, Journal of the American Chemical Society.

[14]  H. Duan,et al.  Plasmonic vesicles of amphiphilic gold nanocrystals: self-assembly and external-stimuli-triggered destruction. , 2011, Journal of the American Chemical Society.

[15]  A Paul Alivisatos,et al.  Continuous imaging of plasmon rulers in live cells reveals early-stage caspase-3 activation at the single-molecule level , 2009, Proceedings of the National Academy of Sciences.

[16]  Sadia Afrin Khan,et al.  Gold nano-popcorn-based targeted diagnosis, nanotherapy treatment, and in situ monitoring of photothermal therapy response of prostate cancer cells using surface-enhanced Raman spectroscopy. , 2010, Journal of the American Chemical Society.

[17]  Sébastien Lecommandoux,et al.  Doxorubicin loaded magnetic polymersomes: theranostic nanocarriers for MR imaging and magneto-chemotherapy. , 2011, ACS Nano.

[18]  Omid C Farokhzad,et al.  Self-assembled targeted nanoparticles: evolution of technologies and bench to bedside translation. , 2011, Accounts of chemical research.

[19]  Jinming Gao,et al.  Tunable, ultrasensitive pH-responsive nanoparticles targeting specific endocytic organelles in living cells. , 2011, Angewandte Chemie.

[20]  Janina Kneipp,et al.  In vivo molecular probing of cellular compartments with gold nanoparticles and nanoaggregates. , 2006, Nano letters.

[21]  Naomi J Halas,et al.  Theranostic nanoshells: from probe design to imaging and treatment of cancer. , 2011, Accounts of chemical research.

[22]  S. Nie,et al.  Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications. , 2008, Chemical Society reviews.

[23]  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.

[24]  Jin-Zhi Du,et al.  Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery. , 2011, Journal of the American Chemical Society.

[25]  Michael J Sailor,et al.  Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. , 2009, Cancer research.

[26]  Dennis E. Discher,et al.  Polymer vesicles : Materials science: Soft surfaces , 2002 .

[27]  John Mendelsohn,et al.  The EGF receptor family as targets for cancer therapy , 2000, Oncogene.

[28]  Sarit S. Agasti,et al.  Gold nanoparticles in chemical and biological sensing. , 2012, Chemical reviews.

[29]  E. Zubarev,et al.  Quantitative replacement of cetyl trimethylammonium bromide by cationic thiol ligands on the surface of gold nanorods and their extremely large uptake by cancer cells. , 2012, Angewandte Chemie.

[30]  S. Nguyen,et al.  Biological evaluation of pH-responsive polymer-caged nanobins for breast cancer therapy. , 2010, ACS nano.

[31]  E. Zubarev,et al.  Amphiphilicity-driven organization of nanoparticles into discrete assemblies. , 2006, Journal of the American Chemical Society.

[32]  L. Liz‐Marzán,et al.  SERS-based diagnosis and biodetection. , 2010, Small.

[33]  Frank Bates,et al.  Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Ick Chan Kwon,et al.  Super pH-sensitive multifunctional polymeric micelle for tumor pH(e) specific TAT exposure and multidrug resistance. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[35]  Younan Xia,et al.  Gold nanocages: from synthesis to theranostic applications. , 2011, Accounts of chemical research.

[36]  B. R. Johnson,et al.  All-optical nanoscale pH meter. , 2006, Nano letters.

[37]  S. Gambhir,et al.  Noninvasive molecular imaging of small living subjects using Raman spectroscopy , 2008, Proceedings of the National Academy of Sciences.

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

[39]  Harm-Anton Klok,et al.  Polymer brushes via surface-initiated controlled radical polymerization: synthesis, characterization, properties, and applications. , 2009, Chemical reviews.

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

[41]  Guoying Zhang,et al.  Efficient synthesis of single gold nanoparticle hybrid amphiphilic triblock copolymers and their controlled self-assembly. , 2012, Journal of the American Chemical Society.

[42]  Paresh Chandra Ray,et al.  Multifunctional plasmonic shell-magnetic core nanoparticles for targeted diagnostics, isolation, and photothermal destruction of tumor cells. , 2012, ACS nano.

[43]  D. Hammer,et al.  Polymersomes: tough vesicles made from diblock copolymers. , 1999, Science.

[44]  B. Cohen,et al.  Rapid cytosolic delivery of luminescent nanocrystals in live cells with endosome-disrupting polymer colloids. , 2010, Nano letters.

[45]  Jeffrey N. Anker,et al.  Biosensing with plasmonic nanosensors. , 2008, Nature materials.

[46]  Zhenxin Wang,et al.  Kinase-catalyzed modification of gold nanoparticles: a new approach to colorimetric kinase activity screening. , 2006, Journal of the American Chemical Society.

[47]  Atsushi Harada,et al.  Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsive to intracellular pH change. , 2003, Angewandte Chemie.

[48]  Alexander D. Q. Li,et al.  Thermosensitive gold nanoparticles. , 2004, Journal of the American Chemical Society.

[49]  Shuo Peng,et al.  Responsive plasmonic assemblies of amphiphilic nanocrystals at oil-water interfaces. , 2010, ACS nano.

[50]  S. Gambhir,et al.  Gold nanoparticles: a revival in precious metal administration to patients. , 2011, Nano letters.

[51]  A. Eisenberg,et al.  Active loading and tunable release of doxorubicin from block copolymer vesicles. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[52]  Michael J. Campolongo,et al.  Building plasmonic nanostructures with DNA. , 2011, Nature nanotechnology.

[53]  Madhavan Nallani,et al.  Biohybrid polymer capsules. , 2009, Chemical reviews.

[54]  V. Rotello,et al.  Monolayer coated gold nanoparticles for delivery applications. , 2012, Advanced drug delivery reviews.

[55]  J. Burdick,et al.  Modular synthesis of biodegradable diblock copolymers for designing functional polymersomes. , 2010, Journal of the American Chemical Society.

[56]  C. Palivan,et al.  Biocompatible functionalization of polymersome surfaces: a new approach to surface immobilization and cell targeting using polymersomes. , 2011, Journal of the American Chemical Society.

[57]  A Paul Alivisatos,et al.  Use of plasmon coupling to reveal the dynamics of DNA bending and cleavage by single EcoRV restriction enzymes , 2006, Proceedings of the National Academy of Sciences.

[58]  Daniele Fava,et al.  Self-assembly of metal-polymer analogues of amphiphilic triblock copolymers. , 2007, Nature materials.

[59]  Sangeeta N. Bhatia,et al.  Intracellular Delivery of Quantum Dots for Live Cell Labeling and Organelle Tracking , 2004 .

[60]  Shuming Nie,et al.  Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings. , 2007, Journal of the American Chemical Society.

[61]  Sébastien Lecommandoux,et al.  A simple method to achieve high doxorubicin loading in biodegradable polymersomes. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[62]  Sarit S. Agasti,et al.  Drug delivery using nanoparticle-stabilized nanocapsules. , 2011, Angewandte Chemie.

[63]  Chun Li,et al.  Exceptionally high payload of doxorubicin in hollow gold nanospheres for near-infrared light-triggered drug release. , 2010, ACS nano.

[64]  H. Dai,et al.  PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation. , 2009, Journal of the American Chemical Society.

[65]  H. Frey,et al.  Gold nanoparticles coated with a thermosensitive hyperbranched polyelectrolyte: towards smart temperature and pH nanosensors. , 2008, Angewandte Chemie.

[66]  Jibin Song,et al.  SERS-Active Nanoparticles for Sensitive and Selective Detection of Cadmium Ion (Cd2+) , 2011 .

[67]  Martin Moskovits,et al.  Mapping local pH in live cells using encapsulated fluorescent SERS nanotags. , 2010, Small.

[68]  W. Smith,et al.  Control of enhanced Raman scattering using a DNA-based assembly process of dye-coded nanoparticles. , 2008, Nature nanotechnology.

[69]  Peidong Yang,et al.  Shape Control of Colloidal Metal Nanocrystals , 2008 .

[70]  J. Vermant,et al.  Directed self-assembly of nanoparticles. , 2010, ACS nano.

[71]  Kevin Burgess,et al.  Fluorescent indicators for intracellular pH. , 2010, Chemical reviews.

[72]  Tao Liu,et al.  Stimuli-Triggered Off/On Switchable Complexation between a Novel Type of Charge-Generation Polymer (CGP) and Gold Nanoparticles for the Sensitive Colorimetric Detection of Hydrogen Peroxide and Glucose , 2011 .

[73]  Jun Wang,et al.  Doxorubicin-tethered responsive gold nanoparticles facilitate intracellular drug delivery for overcoming multidrug resistance in cancer cells. , 2011, ACS nano.

[74]  B. Reinhard,et al.  Illuminating epidermal growth factor receptor densities on filopodia through plasmon coupling. , 2011, ACS nano.

[75]  H. Möhwald,et al.  Directing self-assembly of nanoparticles at water/oil interfaces. , 2004, Angewandte Chemie.

[76]  L. Hawthorn,et al.  Aberrant Expression of Novel and Previously Described Cell Membrane Markers in Human Breast Cancer Cell Lines and Tumors , 2005, Clinical Cancer Research.

[77]  J. Ostrander,et al.  Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles. , 2011, ACS nano.

[78]  P. Messersmith,et al.  Catechol Polymers for pH-Responsive, Targeted Drug Delivery to Cancer Cells , 2011, Journal of the American Chemical Society.

[79]  E. Kumacheva,et al.  Properties and emerging applications of self-assembled structures made from inorganic nanoparticles. , 2010, Nature nanotechnology.

[80]  J. Zhao,et al.  Controlled plasmonic nanostructures for surface-enhanced spectroscopy and sensing. , 2008, Accounts of chemical research.

[81]  Peter Nordlander,et al.  Light-induced release of DNA from gold nanoparticles: nanoshells and nanorods. , 2011, Journal of the American Chemical Society.

[82]  H. Duan,et al.  Self-Assembled Plasmonic Dimers of Amphiphilic Gold Nanocrystals , 2011 .

[83]  H. Duan,et al.  Quantum dots with phenylboronic acid tags for specific labeling of sialic acids on living cells. , 2011, Analytical chemistry.

[84]  Liguang Xu,et al.  Regiospecific plasmonic assemblies for in situ Raman spectroscopy in live cells. , 2012, Journal of the American Chemical Society.

[85]  J. Hafner,et al.  Localized surface plasmon resonance sensors. , 2011, Chemical reviews.

[86]  H. Möhwald,et al.  Fabrication of Multicolor‐Encoded Microspheres by Tagging Semiconductor Nanocrystals to Hydrogel Spheres , 2005 .

[87]  Zhongping Chen,et al.  Combined multimodal optical imaging and targeted gene silencing using stimuli-transforming nanotheragnostics. , 2010, Journal of the American Chemical Society.

[88]  S. Nie,et al.  Stimuli-responsive SERS nanoparticles: conformational control of plasmonic coupling and surface Raman enhancement. , 2009, Journal of the American Chemical Society.

[89]  Karen L. Wooley,et al.  The Importance of Chemistry in Creating Well-Defined Nanoscopic Embedded Therapeutics: Devices Capable of the Dual Functions of Imaging and Therapy , 2011, Accounts of chemical research.

[90]  T. Klar,et al.  Biomolecular Recognition Based on Single Gold Nanoparticle Light Scattering , 2003 .

[91]  Shuming Nie,et al.  Efficient Raman enhancement and intermittent light emission observed in single gold nanocrystals , 1999 .

[92]  George C Schatz,et al.  Structure-activity relationships in gold nanoparticle dimers and trimers for surface-enhanced Raman spectroscopy. , 2010, Journal of the American Chemical Society.

[93]  Xiaohu Gao,et al.  Spectrally tunable leakage-free gold nanocontainers. , 2009, Journal of the American Chemical Society.

[94]  J. Thévenot,et al.  Biologically active polymersomes from amphiphilic glycopeptides. , 2012, Journal of the American Chemical Society.

[95]  Michael J Sailor,et al.  SERS‐Coded Gold Nanorods as a Multifunctional Platform for Densely Multiplexed Near‐Infrared Imaging and Photothermal Heating , 2009, Advanced materials.

[96]  Robert Langer,et al.  Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer. , 2007, Nano letters.

[97]  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.

[98]  Taeghwan Hyeon,et al.  Multifunctional mesoporous silica nanocomposite nanoparticles for theranostic applications. , 2011, Accounts of chemical research.

[99]  Naomi J Halas,et al.  Plasmonics: an emerging field fostered by Nano Letters. , 2010, Nano letters.

[100]  Carsten Sönnichsen,et al.  A molecular ruler based on plasmon coupling of single gold and silver nanoparticles , 2005, Nature Biotechnology.

[101]  Sergio Grinstein,et al.  Sensors and regulators of intracellular pH , 2010, Nature Reviews Molecular Cell Biology.

[102]  Chad A Mirkin,et al.  Aptamer nano-flares for molecular detection in living cells. , 2009, Nano letters.

[103]  Younan Xia,et al.  Gold nanocages: synthesis, properties, and applications. , 2008, Accounts of chemical research.

[104]  M. Bally,et al.  Uptake of adriamycin into large unilamellar vesicles in response to a pH gradient. , 1986, Biochimica et biophysica acta.