Targeted doxorubicin delivery to hepatocarcinoma cells by lactobionic acid-modified laponite nanodisks

In this study, we covalently conjugated polyethylene glycol-linked lactobionic acid (PEG-LA) onto the surface of laponite (LAP) nanodisks for the targeted delivery of doxorubicin (DOX) to liver cancer cells. LAP nanodisks were firstly modified with 3-aminopropyldimethylethoxysilane to introduce amino groups on the surface, and then PEG-LA were successfully conjugated to form targeted LM-PEG-LA nanodisks via EDC chemistry. Finally, the anticancer drug DOX was encapsulated into the synthesized nanocarriers with an exceptionally high loading efficiency of 91.5%. In vitro release studies showed that LM-PEG-LA/DOX could release drugs in a sustained manner with a higher speed under acidic conditions than that under physiological ones. MTT assay results proved that LM-PEG-LA/DOX displayed a significant higher therapeutic efficacy in inhibiting the growth of hepatocellular carcinoma cells (HepG2 cells) than untargeted ones at the same DOX concentration. The targeting specificity of LM-PEG-LA/DOX was further demonstrated by flow cytometric analysis and confocal laser scanning microscopy. The developed LA-modified LAP nanodisks could serve as a targeted carrier for efficient loading and specific delivery of different anticancer drugs to liver cancer cells.

[1]  S. W. Kim,et al.  Tumor targeting RGD conjugated bio-reducible polymer for VEGF siRNA expressing plasmid delivery. , 2014, Biomaterials.

[2]  Xiangyang Shi,et al.  Enhanced in vivo antitumor efficacy of doxorubicin encapsulated within laponite nanodisks. , 2014, ACS applied materials & interfaces.

[3]  Rui Guo,et al.  Lactobionic acid-modified dendrimer-entrapped gold nanoparticles for targeted computed tomography imaging of human hepatocellular carcinoma. , 2014, ACS applied materials & interfaces.

[4]  Mingwu Shen,et al.  Hyaluronic acid-modified hydrothermally synthesized iron oxide nanoparticles for targeted tumor MR imaging. , 2014, Biomaterials.

[5]  Wei Shao,et al.  Carbon nanotube lipid drug approach for targeted delivery of a chemotherapy drug in a human breast cancer xenograft animal model. , 2013, Biomaterials.

[6]  W. Chrzanowski,et al.  Laponite clay as a carrier for in situ delivery of tetracycline , 2013 .

[7]  Gaio Paradossi,et al.  Targeted doxorubicin delivery by chitosan-galactosylated modified polymer microbubbles to hepatocarcinoma cells. , 2013, Colloids and surfaces. B, Biointerfaces.

[8]  Lekha Nair K,et al.  Folic Acid Conjugated δ-Valerolactone-Poly(ethylene glycol) Based Triblock Copolymer as a Promising Carrier for Targeted Doxorubicin Delivery , 2013, PloS one.

[9]  Yun-Xia Li,et al.  Hyaluronic acid-coated nanostructured lipid carriers for targeting paclitaxel to cancer. , 2013, Cancer letters.

[10]  H. Bajaj,et al.  The Layered Silicate, Montmorillonite (MMT) as a Drug Delivery Carrier , 2013 .

[11]  L. Casettari,et al.  Folic Acid Conjugated Chitosan Nanoparticles for Tumor Targeting of Therapeutic and Imaging Agents , 2013 .

[12]  F. González-Nilo,et al.  Computationally efficient methodology for atomic-level characterization of dendrimer-drug complexes: a comparison of amine- and acetyl-terminated PAMAM. , 2013, The journal of physical chemistry. B.

[13]  Mingwu Shen,et al.  Laponite nanodisks as an efficient platform for Doxorubicin delivery to cancer cells. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[14]  Wanshan Ma,et al.  PEGylated Multi-Walled Carbon Nanotubes for Encapsulation and Sustained Release of Oxaliplatin , 2013, Pharmaceutical Research.

[15]  Meifang Zhu,et al.  Encapsulation of amoxicillin within laponite-doped poly(lactic-co-glycolic acid) nanofibers: preparation, characterization, and antibacterial activity. , 2012, ACS applied materials & interfaces.

[16]  J. Watanabe,et al.  Structural and mechanical properties of Laponite-PEG hybrid films. , 2012, Journal of colloid and interface science.

[17]  Su He Wang,et al.  Synthesis of glycoconjugated poly(amindoamine) dendrimers for targeting human liver cancer cells , 2012 .

[18]  Junmin Qian,et al.  Galactosylated poly(ethylene glycol)-b-poly (l-lactide-co-β-malic acid) block copolymer micelles for targeted drug delivery: preparation and in vitro characterization , 2010, International journal of nanomedicine.

[19]  C. Viseras,et al.  Current challenges in clay minerals for drug delivery , 2010 .

[20]  Sun-ho Han,et al.  Inorganic Drug‐Delivery Nanovehicle Conjugated with Cancer‐Cell‐Specific Ligand , 2009 .

[21]  G. Liu,et al.  Targeted folic acid-PEG nanoparticles for noninvasive imaging of folate receptor by MRI. , 2008, Journal of biomedical materials research. Part A.

[22]  Y. B. Choy,et al.  Itraconazole-Laponite: Kinetics and mechanism of drug release , 2008 .

[23]  Y. B. Choy,et al.  Laponite-based nanohybrid for enhanced solubility and controlled release of itraconazole. , 2008, International journal of pharmaceutics.

[24]  A. Pierre,et al.  NMR and IR spectroscopy of silica aerogels with different hydrophobic characteristics , 2005 .

[25]  L. Mathias,et al.  Synthesis and Characterization of Covalently Functionalized Laponite Clay , 2005 .

[26]  Miqin Zhang,et al.  PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[27]  J. Putaux,et al.  Aqueous Dispersions of Silane-Functionalized Laponite Clay Platelets. A First Step toward the Elaboration of Water-Based Polymer/Clay Nanocomposites , 2004 .

[28]  D. Thompson,et al.  Acid-triggered release via dePEGylation of DOPE liposomes containing acid-labile vinyl ether PEG-lipids. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[29]  D. Kerr,et al.  Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[31]  T. V. van Berkel,et al.  Determination of the Upper Size Limit for Uptake and Processing of Ligands by the Asialoglycoprotein Receptor on Hepatocytesin Vitro and in Vivo * , 2001, The Journal of Biological Chemistry.

[32]  Marcus Textor,et al.  Poly(l-lysine)-g-poly(ethylene glycol) Layers on Metal Oxide Surfaces: Surface-Analytical Characterization and Resistance to Serum and Fibrinogen Adsorption , 2001 .

[33]  João Rodrigues,et al.  pH-sensitive Laponite(®)/doxorubicin/alginate nanohybrids with improved anticancer efficacy. , 2014, Acta biomaterialia.

[34]  Xiangyang Shi,et al.  Antitumor efficacy of doxorubicin-loaded laponite/alginate hybrid hydrogels. , 2014, Macromolecular bioscience.

[35]  H. Maeda,et al.  The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. , 2013, Advanced drug delivery reviews.

[36]  W. Marsden.  I and J , 2012 .

[37]  Jeong A. Nam,et al.  Dual-responsive crosslinked pluronic micelles as a carrier to deliver anticancer drug taxol , 2012, Macromolecular Research.

[38]  Yaping Li,et al.  The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma. , 2009, Biomaterials.

[39]  Yokoyama Masayuki,et al.  Polymer micelles as novel drug carrier: Adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer , 1990 .