Multifunctional core-shell upconverting nanoparticles for imaging and photodynamic therapy of liver cancer cells.

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable attention for their application in biomedicine. Here, silica-coated NaGdF(4):Yb,Er/NaGdF(4) nanoparticles with a tetrasubstituted carboxy aluminum phthalocyanine (AlC(4)Pc) photosensitizer covalently incorporated inside the silica shells were prepared and applied in the photodynamic therapy (PDT) and magnetic resonance imaging (MRI) of cancer cells. These UCNP@SiO(2)(AlC(4)Pc) nanoparticles were uniform in size, stable against photosensitizer leaching, and highly efficient in photogenerating cytotoxic singlet oxygen under near-infrared (NIR) light. In vitro studies indicated that these nanoparticles could effectively kill cancer cells upon NIR irradiation. Moreover, the nanoparticles also demonstrated good MR contrast, both in aqueous solution and inside cells. This is the first time that NaGdF(4):Yb,Er/NaGdF(4) upconversion-nanocrystal-based multifunctional nanomaterials have been synthesized and applied in PDT. Our results show that these multifunctional nanoparticles are very promising for applications in versatile imaging diagnosis and as a therapy tool in biomedical engineering.

[1]  Indrajit Roy,et al.  Organically modified silica nanoparticles with covalently incorporated photosensitizer for photodynamic therapy of cancer. , 2007, Nano letters.

[2]  Stanley B. Brown,et al.  The present and future role of photodynamic therapy in cancer treatment. , 2004, The Lancet. Oncology.

[3]  Taeghwan Hyeon,et al.  Nonblinking and Nonbleaching Upconverting Nanoparticles as an Optical Imaging Nanoprobe and T1 Magnetic Resonance Imaging Contrast Agent , 2009 .

[4]  Kemin Wang,et al.  Methylene blue-encapsulated phosphonate-terminated silica nanoparticles for simultaneous in vivo imaging and photodynamic therapy. , 2009, Biomaterials.

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

[6]  F. Tseng,et al.  Mesoporous silica nanoparticles functionalized with an oxygen-sensing probe for cell photodynamic therapy: potential cancer theranostics , 2009 .

[7]  Aleksander Rebane,et al.  Blood-vessel closure using photosensitizers engineered for two-photon excitation , 2008 .

[8]  Paras N. Prasad,et al.  Photosensitization of Singlet Oxygen via Two-Photon-Excited Fluorescence Resonance Energy Transfer in a Water-Soluble Dendrimer , 2005 .

[9]  Ick Chan Kwon,et al.  Tumor specificity and therapeutic efficacy of photosensitizer-encapsulated glycol chitosan-based nanoparticles in tumor-bearing mice. , 2009, Biomaterials.

[10]  Raymond Bonnett,et al.  Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy , 1995 .

[11]  C. Cai,et al.  Synthesis of magnetic, fluorescent and mesoporous core-shell-structured nanoparticles for imaging, targeting and photodynamic therapy , 2011 .

[12]  A. Vogel,et al.  Mechanisms of pulsed laser ablation of biological tissues. , 2003, Chemical reviews.

[13]  Steffen Hackbarth,et al.  Singlet Oxygen Quantum Yields of Different Photosensitizers in Polar Solvents and Micellar Solutions , 1998 .

[14]  R. Gurny,et al.  State of the art in the delivery of photosensitizers for photodynamic therapy. , 2002, Journal of photochemistry and photobiology. B, Biology.

[15]  Chengzhong Yu,et al.  Small mesoporous silica nanoparticles as carriers for enhanced photodynamic therapy. , 2011, Chemistry, an Asian journal.

[16]  Zhengquan Li,et al.  Seed-mediated synthesis of NaY F4:Y b, Er/NaGdF4 nanocrystals with improved upconversion fluorescence and MR relaxivity , 2010, Nanotechnology.

[17]  Yibin Kang,et al.  Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso‐Tetraphenyl porphine (TPP) for Photodynamic Therapy , 2011 .

[18]  Zhang Yong,et al.  Upconverting nanoparticles as nanotransducers for photodynamic therapy in cancer cells. , 2008, Nanomedicine.

[19]  Louis A. Cuccia,et al.  Synthesis, Characterization, and Spectroscopy of NaGdF4: Ce3+, Tb3+/NaYF4 Core/Shell Nanoparticles , 2007 .

[20]  T J Dougherty,et al.  PHOTOSENSITIZERS: THERAPY AND DETECTION OF MALIGNANT TUMORS , 1987, Photochemistry and photobiology.

[21]  Bo Tang,et al.  Multifunctional core-shell nanoparticles as highly efficient imaging and photosensitizing agents. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[22]  Maria Strømme,et al.  Mesoporous silica particles induce size dependent effects on human dendritic cells. , 2007, Nano letters.

[23]  B. Pogue,et al.  Liposomal delivery of photosensitising agents , 2005, Expert opinion on drug delivery.

[24]  S. Lacombe,et al.  Singlet oxygen in microporous silica xerogel: quantum yield and oxidation at the gas-solid interface. , 2007, Chemphyschem : a European journal of chemical physics and physical chemistry.

[25]  Chung-Yuan Mou,et al.  Size effect on cell uptake in well-suspended, uniform mesoporous silica nanoparticles. , 2009, Small.

[26]  Manoj Kumar,et al.  Versatile photosensitizers for photodynamic therapy at infrared excitation. , 2007, Journal of the American Chemical Society.

[27]  Zhuang Liu,et al.  Near-infrared light induced in vivo photodynamic therapy of cancer based on upconversion nanoparticles. , 2011, Biomaterials.

[28]  François Guillemin,et al.  Nanoparticles as vehicles for delivery of photodynamic therapy agents. , 2008, Trends in biotechnology.

[29]  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.

[30]  Hui Guo,et al.  Mesoporous-silica-coated up-conversion fluorescent nanoparticles for photodynamic therapy. , 2009, Small.

[31]  Cornelus F. van Nostrum,et al.  Polymeric micelles to deliver photosensitizers for photodynamic therapy. , 2004 .

[32]  C. M. Allen,et al.  Photodynamic therapeutics: basic principles and clinical applications. , 1999, Drug discovery today.

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

[34]  Tymish Y. Ohulchanskyy,et al.  Combined Optical and MR Bioimaging Using Rare Earth Ion Doped NaYF4 Nanocrystals , 2009 .

[35]  T. Dougherty,et al.  A brief history of clinical photodynamic therapy development at Roswell Park Cancer Institute. , 1996, Journal of clinical laser medicine & surgery.