Fabrication of multifunctional layer-by-layer nanocapsules toward the design of theragnostic nanoplatform.

Self-assembled polymeric nanocapsules (NCs) that incorporate dendrimer porphyrin (DP) in the shells and superparamagnetic iron oxide nanoparticles (SPIONs) in the cores are fabricated to create a theragnostic platform for the application in photodynamic therapy (PDT) and magnetic resonance imaging (MRI). SPIONs-embedded polystyrene NPs (SPIONs@PS) are used as a template to build up multilayered NCs. The formation of PAH/DP multilayer on the SPIONs@PS is monitored by zeta-pential and fluorescence emission measurement, because the porphyrin unit in the core of DP has strong red fluorescence emission. NCs have strong enough magnetic property (>20 emu/g) for MRI application with typical superparamagnetic behavior, where the linear correlation of R2 and Fe concentration at diluted conditions led to corresponding T2 relaxivity coefficient (r2) value of 93.5 mM(-1) s(-1). Cell viability study upon light irradiation reveals that NCs can successfully work in photosensitizer formulation for PDT.

[1]  Sangjin Park,et al.  Drug-loaded superparamagnetic iron oxide nanoparticles for combined cancer imaging and therapy in vivo. , 2008, Angewandte Chemie.

[2]  Shuming Nie,et al.  Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery , 2006, Molecular Cancer Therapeutics.

[3]  J. Majoral,et al.  Dendrimer therapeutics: covalent and ionic attachments , 2012 .

[4]  Kwangmeyung Kim,et al.  Tumor-targeting multi-functional nanoparticles for theragnosis: new paradigm for cancer therapy. , 2012, Advanced drug delivery reviews.

[5]  Atsushi Harada,et al.  Formation of Polyion Complex Micelles in an Aqueous Milieu from a Pair of Oppositely-Charged Block Copolymers with Poly(ethylene glycol) Segments , 1995 .

[6]  I. Kwon,et al.  In situ dose amplification by apoptosis-targeted drug delivery. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

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

[8]  N. Gu,et al.  Effective PEGylation of Iron Oxide Nanoparticles for High Performance In Vivo Cancer Imaging , 2011 .

[9]  M. Shekhar,et al.  Surfactant-polymer nanoparticles enhance the effectiveness of anticancer photodynamic therapy. , 2008, Molecular pharmaceutics.

[10]  Gang Bao,et al.  Coating optimization of superparamagnetic iron oxide nanoparticles for high T2 relaxivity. , 2010, Nano letters.

[11]  Gang Zheng,et al.  Self-assembled porphyrin nanodiscs with structure-dependent activation for phototherapy and photodiagnostic applications. , 2013, ACS nano.

[12]  Jinwoo Cheon,et al.  Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology. , 2008, Accounts of chemical research.

[13]  Jonathan F. Lovell,et al.  Lipoprotein-Inspired Nanoparticles for Cancer Theranostics , 2011, Accounts of chemical research.

[14]  Controlled clustering of superparamagnetic nanoparticles using block copolymers: design of new contrast agents for magnetic resonance imaging. , 2005, Journal of the American Chemical Society.

[15]  John V Frangioni,et al.  New technologies for human cancer imaging. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Jinwoo Cheon,et al.  Chemical design of nanoparticle probes for high-performance magnetic resonance imaging. , 2008, Angewandte Chemie.

[17]  Jung-Kyo Cho,et al.  Thermosensitive/magnetic poly(organophosphazene) hydrogel as a long-term magnetic resonance contrast platform. , 2012, Biomaterials.

[18]  Ick Chan Kwon,et al.  Multifunctional nanoparticles for multimodal imaging and theragnosis. , 2012, Chemical Society reviews.

[19]  Y. Nagasaki,et al.  Stimuli-responsive smart nanogels for cancer diagnostics and therapy. , 2010, Nanomedicine.

[20]  M. Ferrari.  Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[21]  W. Jang,et al.  Polymeric supramolecular systems for drug delivery , 2010 .

[22]  R. Jain,et al.  Photodynamic therapy for cancer , 2003, Nature Reviews Cancer.

[23]  Yun Chi,et al.  Iridium-complex-functionalized Fe3O4/SiO2 core/shell nanoparticles: a facile three-in-one system in magnetic resonance imaging, luminescence imaging, and photodynamic therapy. , 2008, Small.

[24]  Gero Decher,et al.  Fuzzy Nanoassemblies: Toward Layered Polymeric Multicomposites , 1997 .

[25]  Hauke Kloust,et al.  Relaxivity optimization of a PEGylated iron-oxide-based negative magnetic resonance contrast agent for T₂-weighted spin-echo imaging. , 2012, ACS nano.

[26]  Satoko Kawauchi,et al.  Polyion complex micelles for photodynamic therapy: incorporation of dendritic photosensitizer excitable at long wavelength relevant to improved tissue-penetrating property. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[27]  W. Koh,et al.  Photosensitizing hollow nanocapsules for combination cancer therapy. , 2011, Angewandte Chemie.

[28]  J. Cheon,et al.  Theranostic magnetic nanoparticles. , 2011, Accounts of chemical research.

[29]  Min Gyu Kim,et al.  Redox-transmetalation process as a generalized synthetic strategy for core-shell magnetic nanoparticles. , 2005, Journal of the American Chemical Society.

[30]  Bing Xu,et al.  Synthesis and cellular uptake of porphyrin decorated iron oxide nanoparticles-a potential candidate for bimodal anticancer therapy. , 2005, Chemical communications.

[31]  Kazunori Kataoka,et al.  Supramolecular nanodevices: from design validation to theranostic nanomedicine. , 2011, Accounts of chemical research.

[32]  Yongmin Chang,et al.  Gadolinium oxide nanoparticles as potential multimodal imaging and therapeutic agents. , 2013, Current topics in medicinal chemistry.

[33]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[34]  O. Velev,et al.  Emulsion-Based Synthesis of Reversibly Swellable, Magnetic Nanoparticle-Embedded Polymer Microcapsules , 2006 .

[35]  Q. Pankhurst,et al.  Imaging applications of nanotechnology in cancer , 2009, Targeted Oncology.

[36]  David A Russell,et al.  Intracellular photodynamic therapy with photosensitizer-nanoparticle conjugates: cancer therapy using a ‘Trojan horse’ , 2006, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[37]  T. Aida,et al.  Dendrimer Generation Effects on Photodynamic Efficacy of Dendrimer Porphyrins and Dendrimer-Loaded Supramolecular Nanocarriers , 2007 .

[38]  Hongyou Fan,et al.  Surfactant-assisted synthesis of water-soluble and biocompatible semiconductor quantum dot-micelles , 2005, SPIE BiOS.

[39]  Satoko Kawauchi,et al.  Supramolecular nanocarrier of anionic dendrimer porphyrins with cationic block copolymers modified with polyethylene glycol to enhance intracellular photodynamic efficacy. , 2005, Angewandte Chemie.

[40]  Frank Caruso,et al.  Template Synthesis of Nanostructured Materials via Layer-by-Layer Assembly† , 2008 .

[41]  Hongchen Gu,et al.  Development of high magnetization Fe3O4/polystyrene/silica nanospheres via combined miniemulsion/emulsion polymerization. , 2006, Journal of the American Chemical Society.

[42]  Swadeshmukul Santra,et al.  Synthesis of water-dispersible fluorescent, radio-opaque, and paramagnetic CdS:Mn/ZnS quantum dots: a multifunctional probe for bioimaging. , 2005, Journal of the American Chemical Society.

[43]  Jing Lin,et al.  Photosensitizer-conjugated magnetic nanoparticles for in vivo simultaneous magnetofluorescent imaging and targeting therapy. , 2011, Biomaterials.

[44]  Hua Ai,et al.  Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. , 2006, Nano letters.

[45]  Xing-Jie Liang,et al.  Theranostic nanoparticles engineered for clinic and pharmaceutics. , 2011, Accounts of chemical research.

[46]  Jinwoo Cheon,et al.  Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging , 2007, Nature Medicine.

[47]  J. Kershaw,et al.  SPIO-PICsome: development of a highly sensitive and stealth-capable MRI nano-agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles (PICsomes). , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[48]  H. Chan,et al.  Facile fabrication of AgCl@polypyrrole-chitosan core-shell nanoparticles and polymeric hollow nanospheres. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[49]  Ajay Kumar Gupta,et al.  Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. , 2005, Biomaterials.

[50]  Jinwoo Cheon,et al.  Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. , 2005, Journal of the American Chemical Society.