Acid degradable ZnO quantum dots as a platform for targeted delivery of an anticancer drug

Efficacious chemotherapy mainly hinges on the tumor-specific delivery of anticancer drugs. Herein we report a successful fabrication of highly photoluminescent and water dispersible ZnO quantum dotsvia a new ligand exchange free strategy. In addition to bioimaging, ZnO QDs have also been evaluated as a platform for targeted and pH responsive intracellular delivery of an anticancer drug. The cancer targeting feature is endowed by conjugating folic acid on to the surface of ZnO–NH2 QDs via an amidation reaction. Doxorubicin (DOX) is then successfully loaded onto the folic acid functionalized ZnO QDs by capitalizing on its marked tendency towards the formation of metal complexes. Drug loaded ZnO-FA QDs remain stable at physiological pH but readily disintegrate in the mildly acidic intracellular environment of cancer cells as validated by a drug release profile, confocal microscopy and a cell-cytotoxicity assay. Compared to the conventional drug nanovector, ZnO-FA QDs themselves manifest a significant therapeutic activity after reaching their targeted site, therefore, combined DOX and ZnO QDs can be more efficacious than either alone. Hence, this approach provides a valuable ZnO QDs-based nanovector that can simultaneously realize targeting, diagnosis, and therapy of cancer cells.

[1]  Aifei Wang,et al.  pH-Triggered controlled drug release from mesoporous silica nanoparticles via intracelluar dissolution of ZnO nanolids. , 2011, Journal of the American Chemical Society.

[2]  K. Jeyasubramanian,et al.  Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[3]  Baoan Chen,et al.  A strategy for ZnO nanorod mediated multi-mode cancer treatment. , 2011, Biomaterials.

[4]  R. Cardiff,et al.  Copper-doxorubicin as a nanoparticle cargo retains efficacy with minimal toxicity. , 2010, Molecular pharmaceutics.

[5]  L. Balan,et al.  Biocompatible and stable ZnO quantum dots generated by functionalization with siloxane-core PAMAM dendrons , 2010 .

[6]  Deepthy Menon,et al.  Role of size scale of ZnO nanoparticles and microparticles on toxicity toward bacteria and osteoblast cancer cells , 2009, Journal of materials science. Materials in medicine.

[7]  Klaas Nicolay,et al.  Paramagnetic lipid-coated silica nanoparticles with a fluorescent quantum dot core: a new contrast agent platform for multimodality imaging. , 2008, Bioconjugate chemistry.

[8]  Shuming Nie,et al.  Bioconjugated quantum dots for in vivo molecular and cellular imaging. , 2008, Advanced drug delivery reviews.

[9]  Juan L. Vivero-Escoto,et al.  Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. , 2008, Advanced drug delivery reviews.

[10]  L. Balan,et al.  Synthesis and characterization of water-soluble ZnO quantum dots prepared through PEG-siloxane coating , 2008 .

[11]  Yongyao Xia,et al.  Stable aqueous ZnO@polymer core-shell nanoparticles with tunable photoluminescence and their application in cell imaging. , 2008, Journal of the American Chemical Society.

[12]  S. Rakshit,et al.  Trap-state dynamics in visible-light-emitting ZnO:MgO nanocrystals , 2008 .

[13]  Xiaohu Gao,et al.  Emerging application of quantum dots for drug delivery and therapy , 2008 .

[14]  U. Banin,et al.  Folate-mediated tumor cell uptake of quantum dots entrapped in lipid nanoparticles. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[15]  J. Karp,et al.  Nanocarriers as an Emerging Platform for Cancer Therapy , 2022 .

[16]  Jing Sun,et al.  Stable aqueous dispersion of ZnO quantum dots with strong blue emission via simple solution route. , 2007, Journal of the American Chemical Society.

[17]  D. S. Bohle,et al.  The relationship of oxygen binding and peroxide sites and the fluorescent properties of zinc oxide semiconductor nanocrystals. , 2007, Journal of the American Chemical Society.

[18]  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.

[19]  B. Kristal,et al.  Zinc Irreversibly Damages Major Enzymes of Energy Production and Antioxidant Defense Prior to Mitochondrial Permeability Transition* , 2007, Journal of Biological Chemistry.

[20]  Kelly Y. Kim,et al.  Nanotechnology platforms and physiological challenges for cancer therapeutics , 2007 .

[21]  Emril Mohamed Ali,et al.  Controlled photostability of luminescent nanocrystalline ZnO solution for selective detection of aldehydes. , 2007, Chemical communications.

[22]  Volker Wagner,et al.  The emerging nanomedicine landscape , 2006, Nature Biotechnology.

[23]  Ruth Duncan,et al.  Polymer conjugates as anticancer nanomedicines , 2006, Nature Reviews Cancer.

[24]  H. Xiong,et al.  Polymerization Initiated by Inherent Free Radicals on Nanoparticle Surfaces: A Simple Method of Obtaining Ultrastable (ZnO)Polymer Core–Shell Nanoparticles with Strong Blue Fluorescence , 2006 .

[25]  P. Holloway,et al.  Enhanced and stable green emission of ZnO nanoparticles by surface segregation of Mg , 2006, Nanotechnology.

[26]  C. Xie,et al.  Zn2+ release from zinc and zinc oxide particles in simulated uterine solution. , 2006, Colloids and surfaces. B, Biointerfaces.

[27]  Nick S. Norberg,et al.  Influence of surface modification on the luminescence of colloidal ZnO nanocrystals. , 2005, The journal of physical chemistry. B.

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

[29]  V. Torchilin.  Recent advances with liposomes as pharmaceutical carriers , 2005, Nature Reviews Drug Discovery.

[30]  Tim Liedl,et al.  Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. , 2005, Nano letters.

[31]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[32]  S. Bhatia,et al.  Probing the Cytotoxicity Of Semiconductor Quantum Dots. , 2004, Nano letters.

[33]  K. Edwards,et al.  Formation of transition metal-doxorubicin complexes inside liposomes. , 2002, Biochimica et biophysica acta.

[34]  P. Couvreur,et al.  Nanoparticles in cancer therapy and diagnosis. , 2002, Advanced drug delivery reviews.

[35]  H. Kozłowski,et al.  Solution structure of iron(III)-anthracycline complexes. , 1999, Journal of medicinal chemistry.

[36]  H. Kozłowski,et al.  How Fe3+ binds anthracycline antitumour compounds. The myth and the reality of a chemical sphinx. , 1999, Journal of inorganic biochemistry.

[37]  Marc A. Anderson,et al.  Semiconductor clusters in the sol-gel process: quantized aggregation, gelation, and crystal growth in concentrated zinc oxide colloids , 1991 .

[38]  A. Garnier-Suillerot,et al.  Metal anthracycline complexes as a new class of anthracycline derivatives. Pd(II)-adriamycin and Pd(II)-daunorubicin complexes: physicochemical characteristics and antitumor activity. , 1986, Biochemistry.

[39]  M. Reggiani,et al.  ON PHYSICO-CHEMICAL INTERACTIONS BETWEEN DAUNOMYCIN AND NUCLEIC ACIDS. , 1965, Biochimica et biophysica acta.