pH-Sensitive ZnO Quantum Dots-Doxorubicin Nanoparticles for Lung Cancer Targeted Drug Delivery.

In this paper, we reported a ZnO quantum dots-based pH-responsive drug delivery platform for intracellular controlled release of drugs. Acid-decomposable, luminescent aminated ZnO quantum dots (QDs) were synthesized as nanocarriers with ultrasmall size (∼3 nm). The dicarboxyl-terminated poly(ethylene glycol) (PEG) had been introduced to NH2-ZnO QDs, which rendered it stable under physiological fluid. Moreover, a targeting ligand, hyaluronic acid (HA), was conjugated to ZnO QDs for specifically binding to the overexpressed glycoprotein CD44 by cancer cells. Doxorubicin (DOX) molecules were successfully loaded to PEG functionalized ZnO QDs via formation of metal-DOX complex and covalent interactions. The pH-sensitive ZnO QDs dissolved to Zn(2+) in acidic endosome/lysosome after uptake by cancer cells, which triggered dissociation of the metal-drug complex and a controlled DOX release. As result, a synergistic therapy was achieved due to incorporation of the antitumor effect of Zn(2+) and DOX.

[1]  Helmuth Möhwald,et al.  ZnO-Based Nanoplatforms for Labeling and Treatment of Mouse Tumors without Detectable Toxic Side Effects. , 2016, ACS nano.

[2]  Chenjie Xu,et al.  Ultrasensitive Profiling of Metabolites Using Tyramine-Functionalized Graphene Quantum Dots. , 2016, ACS nano.

[3]  Z. Wang,et al.  Sericin/Dextran Injectable Hydrogel as an Optically Trackable Drug Delivery System for Malignant Melanoma Treatment. , 2016, ACS applied materials & interfaces.

[4]  Dan Du,et al.  Hyaluronic Acid-Modified Multifunctional Q-Graphene for Targeted Killing of Drug-Resistant Lung Cancer Cells. , 2016, ACS applied materials & interfaces.

[5]  Jie Feng,et al.  Multifunctional Mesoporous Silica Nanoparticles Based on Charge-Reversal Plug-Gate Nanovalves and Acid-Decomposable ZnO Quantum Dots for Intracellular Drug Delivery. , 2015, ACS applied materials & interfaces.

[6]  Haizheng Zhong,et al.  Small GSH-Capped CuInS2 Quantum Dots: MPA-Assisted Aqueous Phase Transfer and Bioimaging Applications. , 2015, ACS applied materials & interfaces.

[7]  Jia-cong Shen,et al.  Protein-gold hybrid nanocubes for cell imaging and drug delivery. , 2015, ACS applied materials & interfaces.

[8]  Rafiq Ahmad,et al.  Enhanced anticancer potency using an acid-responsive ZnO-incorporated liposomal drug-delivery system. , 2015, Nanoscale.

[9]  Yan Wang,et al.  Hyaluronic acid oligosaccharide modified redox-responsive mesoporous silica nanoparticles for targeted drug delivery. , 2014, ACS applied materials & interfaces.

[10]  Xiaohong Li,et al.  Folate-decorated and reduction-sensitive micelles assembled from amphiphilic polymer-camptothecin conjugates for intracellular drug delivery. , 2014, Molecular pharmaceutics.

[11]  N. Dantas,et al.  Controlling the cytotoxicity of CdSe magic-sized quantum dots as a function of surface defect density. , 2014, Nano letters.

[12]  Yang Song,et al.  Hyaluronic acid-decorated graphene oxide nanohybrids as nanocarriers for targeted and pH-responsive anticancer drug delivery. , 2014, ACS applied materials & interfaces.

[13]  G. Zhu,et al.  pH dictates the release of hydrophobic drug cocktail from mesoporous nanoarchitecture. , 2013, ACS applied materials & interfaces.

[14]  Liangfang Zhang,et al.  Nanoparticle-stabilized liposomes for pH-responsive gastric drug delivery. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[15]  K. Yuan,et al.  Efficiency and air-stability improvement of flexible inverted polymer solar cells using ZnO/poly(ethylene glycol) hybrids as cathode buffer layers. , 2013, ACS applied materials & interfaces.

[16]  Jin Xie,et al.  RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors. , 2013, ACS nano.

[17]  Jesse D. Marshall,et al.  Optical strategies for sensing neuronal voltage using quantum dots and other semiconductor nanocrystals. , 2013, ACS nano.

[18]  Younan Xia,et al.  A thermoresponsive bubble-generating liposomal system for triggering localized extracellular drug delivery. , 2013, ACS nano.

[19]  Rafiq Ahmad,et al.  Chemical and Biological Sensors Based on Metal Oxide Nanostructures , 2012 .

[20]  Ling-hong Zhu,et al.  Gold nanocluster-conjugated amphiphilic block copolymer for tumor-targeted drug delivery. , 2012, ACS applied materials & interfaces.

[21]  Yan Liu,et al.  Aqueous synthesis of glutathione-capped CdTe/CdS/ZnS and CdTe/CdSe/ZnS core/shell/shell nanocrystal heterostructures. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[22]  Jun Lin,et al.  Up-conversion cell imaging and pH-induced thermally controlled drug release from NaYF4/Yb3+/Er3+@hydrogel core-shell hybrid microspheres. , 2012, ACS nano.

[23]  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.

[24]  Huijun Zhao,et al.  Acid degradable ZnO quantum dots as a platform for targeted delivery of an anticancer drug , 2011 .

[25]  Xinli Liu,et al.  Characterization of CD44-mediated cancer cell uptake and intracellular distribution of hyaluronan-grafted liposomes. , 2011, Molecular pharmaceutics.

[26]  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.

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

[28]  Ran Shen,et al.  Multifunctional conjugates to prepare nucleolar-targeting CdS quantum dots. , 2010, Journal of the American Chemical Society.

[29]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[30]  Haijiao Zhang,et al.  Nanosized zinc oxide particles induce neural stem cell apoptosis , 2009, Nanotechnology.

[31]  Benjamin Gilbert,et al.  Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. , 2008, ACS nano.

[32]  J. Visvader,et al.  Cancer stem cells in solid tumours: accumulating evidence and unresolved questions , 2008, Nature Reviews Cancer.

[33]  Shuming Nie,et al.  Oxidative quenching and degradation of polymer-encapsulated quantum dots: new insights into the long-term fate and toxicity of nanocrystals in vivo. , 2008, Journal of the American Chemical Society.

[34]  Monty Liong,et al.  Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. , 2008, ACS nano.

[35]  Janet Layne,et al.  Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles , 2008, Nanotechnology.

[36]  K. Kröncke.  Cellular stress and intracellular zinc dyshomeostasis. , 2007, Archives of biochemistry and biophysics.

[37]  M. Young,et al.  Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles. , 2006, Journal of the American Chemical Society.

[38]  S. Gambhir,et al.  Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics , 2005, Science.

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

[40]  Silvio Aime,et al.  Compartmentalization of a gadolinium complex in the apoferritin cavity: a route to obtain high relaxivity contrast agents for magnetic resonance imaging. , 2002, Angewandte Chemie.