Skip to main content
Log in

New generation of β-cyclodextrin-chitosan nanoparticles encapsulated quantum dots loaded with anticancer drug for tumor-target drug delivery and imaging of cancer cells

  • Research Paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

The objective of this study was to report the drug delivery system that can integrate the functional building blocks for optical pH-sensing, cancer cell imaging and controlled drug release into a single nanoparticle. The CD/SAHA-QDs-CS/FA nanoparticles were prepared by in-situ immobilization of ZnSe/ZnS quantum dots (QDs) in β-cyclodextrin (CD) and chitosan (CS) polymer loaded with suberoylanilide hydroxamic acid (SAHA). Synthetic CD/SAHA-QDs-CS/FA nanoparticles were approximately 100 nm in size and with blue fluorescence. The drug encapsulation efficiency of nanoparticles was 22.36 % and the encapsulated drug was released via a controlled release mechanism after a 9 h plateau was reached. The efficiency of the drug release in tumor microenvironments (pH 5.3 buffer solutions) was higher than that in physiological pH 7.4. In vitro cytotoxicity assay results showed that the blank nanoparticles had no cytotoxicity and therefore can be used as the fluorescence tracer, and the SAHA-encapsulated nanoparticles expressed an anticancer effect. Confocal microscopy and in vivo imaging studies showed that the developed nanoparticles had cytotoxicity in resistant cancer cells and preferentially accumulated in tumors. CD/SAHA-QDs-CS/FA nanoparticles with excellent long-term optical properties have great prospects for the development of targeting tracers and anti-tumor biomedical research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  • Abedini F, Hosseinkhani H, Ismail M, Domb AJ, Omar AR, Chong PP, Hong P-D, Yu D-S, Farber I-Y (2008) Cationized dextran nanoparticle-encapsulated CXCR4 -siRNA enhanced correlation between CXCR4 expression and serum alkaline phosphatase in a mouse model of colorectal cancer. Int J Nanomed 7:4159–4168

    Google Scholar 

  • Adeli M, Kalantari M, Parsamanesh M, Sadeghi E, Mahmoudi M (2011) Synthesis of new hybrid nanomaterials: promising systems for cancer therapy. Nanomed-Nanotechnol 7:806–817

    Article  CAS  Google Scholar 

  • Algar WR, Tavares AJ, Krull UJ (2010) Beyond labels: a review of the application of quantum dots as integrated components of assays, bioprobes, and biosensors utilizing optical transduction. Anal Chim Acta 673:1–25

    Article  CAS  Google Scholar 

  • Barua S, Rege K (2010) The influence of mediators of intracellular trafficking on transgene expression efficacy of polymer–plasmid DNA complexes. Biomaterials 31:5894–5902

    Article  CAS  Google Scholar 

  • Byers RJ, Hitchman ER (2011) Quantum dots brighten biological imaging. Prog Histochem Cyto 45:201–237

    Article  Google Scholar 

  • Chandra S, Barick KC, Bahadur D (2011) Oxide and hybrid nanostructures for therapeutic applications. Adv Drug Deliver Rev 63:1267–1281

    Article  CAS  Google Scholar 

  • Chen C, Peng J, Xia H-S, Yang G-F, Wu Q-S, Chen L-D, Zeng L-B, Zhang Z-L, Pang D-W, Li Y (2009) Quantum dots-based immunofluorescence technology for the quantitative determination of HER2 expression in breast cancer. Biomaterials 30:2912–2918

    Article  CAS  Google Scholar 

  • Daneshgar P, Moosavi-Movahedi AA, Norouzi P, Ganjali MR, Madadkar-Sobhani A, Saboury AA (2009) Molecular interaction of human serum albumin with paracetamol: spectroscopic and molecular modeling studies. Int J Biol Macromol 45:129–134

    Article  CAS  Google Scholar 

  • Fan L, Li M, Lv Z, Sun M, Luo C, Lu F, Qiu H (2012) Fabrication of magnetic chitosan nanoparticles grafted with β-cyclodextrin as effective adsorbents toward hydroquinol. Colloid Surface B 95:42–49

    Article  Google Scholar 

  • Gantt SL, Gattis SG, Fierke CA (2006) Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion. Biochemistry 45:6170–6178

    Article  CAS  Google Scholar 

  • Geszke, Moritz M (2013) Quantum dots as versatile probes in medical sciences: synthesis, modification and properties. Mat Sci Eng C 33:1008–1021

    Article  Google Scholar 

  • Geszke M, Murias M, Balan L, Medjahdi G, Korczynski J, Moritz M, Lulek J, Schneider R (2011) Folic acid-conjugated core/shell ZnS:Mn/ZnS quantum dots as targeted probes for two photon fluorescence imaging of cancer cells. Acta Biomater 7:1327–1338

    Article  CAS  Google Scholar 

  • Ghosh D, Ghosh S, Saha A (2010) Quantum dot based probing of mannitol: an implication in clinical diagnostics. Anal Chim Acta 675:165–169

    Article  CAS  Google Scholar 

  • Gong H, Lin Z, Zhai G, Liu K, Wang Z, Huo X, Li J, Huang H, Wang M (2008) Preparation of mercaptoacetic acid-capped ZnSe core–shell nanocrystals by hydrothermal method. Ceram Int 34:1085–1087

    Article  CAS  Google Scholar 

  • Griffith DM, Szőcs B, Keogh T, Suponitsky KY, Farkas E, Buglyó P, Marmion CJ (2011) Suberoylanilide hydroxamic acid, a potent histone deacetylase inhibitor; its X-ray crystal structure and solid state and solution studies of its Zn(II), Ni(II), Cu(II) and Fe(III) complexes. J Inorg Biochem 105:763–769

    Article  CAS  Google Scholar 

  • Haley B, Frenkel E (2008) Nanoparticles for drug delivery in cancer treatment. Urol Oncol 26:57–64

    Article  CAS  Google Scholar 

  • Higuchi T, Connors KA (1965) Phase solubility techniques. Adv Anal Chem Instrum 4:117–212

    CAS  Google Scholar 

  • Hosseinkhani H, Kushibiki T, Matsumoto K, Nakamura T, Tabata Y (2006) Enhanced suppression of tumor growth using a combination of NK4 plasmid DNA-PEG engrafted cationized dextran complex and ultrasound irradiation. Cancer Gene Ther 13:479–489

    Article  CAS  Google Scholar 

  • Jamieson T, Bakhshi R, Petrova D, Pocock R, Imani M, Seifalian AM (2007) Biological applications of quantum dots. Biomaterials 28:4717–4732

    Article  CAS  Google Scholar 

  • Jingou J, Shilei H, Weiqi L, Danjun W, Tengfei W, Yi X (2011) Preparation, characterization of hydrophilic and hydrophobic drug in combine loaded chitosan/cyclodextrin nanoparticles and in vitro release study. Colloid Surface B 83:103–107

    Article  Google Scholar 

  • Konishi M, Tabata Y, Kariya M, Hosseinkhani H, Suzuki A, Fukuhara K, Mandai M, Takakura K, Fujii S (2005) In vivo anti-tumor effect of dual release of cisplatin and adriamycin from biodegradable gelatin hydrogel. J Control Release 103:7–19

    Article  CAS  Google Scholar 

  • Krauland AH, Alonso MJ (2007) Chitosan/cyclodextrin nanoparticles as macromolecular drug delivery system. Int J Pharm 340:134–142

    Article  CAS  Google Scholar 

  • Mahmoudi M, Hosseinkhani H, Hosseinkhani M, Boutry S, Simchi A, Journeay WS, Subramani K, Laurent S (2010) Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advancement of clinical regenerative medicine. Chem Rev 111:253–280

    Article  Google Scholar 

  • Mathew ME, Mohan JC, Manzoor K, Nair SV, Tamura H, Jayakumar R (2010) Folate conjugated carboxymethyl chitosan–manganese doped zinc sulphide nanoparticles for targeted drug delivery and imaging of cancer cells. Carbohyd Polym 80:442–448

    Article  CAS  Google Scholar 

  • Mattoussi H, Palui G, Na HB (2012) Luminescent quantum dots as platforms for probing in vitro and in vivo biological processes. Adv Drug Deliver Rev 64:138–166

    Article  CAS  Google Scholar 

  • Ohtsuki A, Kimura MT, Minoshima M, Suzuki T, Ikeda M, Bando T, Nagase H, K-i Shinohara, Sugiyama H (2009) Synthesis and properties of PI polyamide–SAHA conjugate. Tetrahedron Lett 50:7288–7292

    Article  CAS  Google Scholar 

  • Oluwafemi OS, Revaprasadu N, Adeyemi OO (2010) A facile “green” synthesis of ascorbic acid-capped ZnSe nanoparticles. Colloid Surface B 79:126–130

    Article  CAS  Google Scholar 

  • Pan J, Feng S–S (2009) Targeting and imaging cancer cells by Folate-decorated, quantum dots (QDs)- loaded nanoparticles of biodegradable polymers. Biomaterials 30:1176–1183

    Article  CAS  Google Scholar 

  • Parveen S, Misra R, Sahoo SK (2012) Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomed-Nanotechnol 8:147–166

    Article  CAS  Google Scholar 

  • Prabaharan M, Jayakumar R (2009) Chitosan-graft-β-cyclodextrin scaffolds with controlled drug release capability for tissue engineering applications. Int J Biol Macromol 44:320–325

    Article  CAS  Google Scholar 

  • Richon VM, Garcia-Vargas J, Hardwick JS (2009) Development of vorinostat: current applications and future perspectives for cancer therapy. Cancer Lett 280:201–210

    Article  CAS  Google Scholar 

  • Sahay G, Alakhova DY, Kabanov AV (2010) Endocytosis of nanomedicines. J Control Release 145:182–195

    Article  CAS  Google Scholar 

  • Sahoo SK, Labhasetwar V (2003) Nanotech approaches to drug delivery and imaging. Drug Discov Today 8:1112–1120

    Article  CAS  Google Scholar 

  • Sajomsang W, Gonil P, Ruktanonchai UR, Pimpha N, Sramala I, Nuchuchua O, Saesoo S, Chaleawlert-umpon S, Puttipipatkhachorn S (2011) Self-aggregates formation and mucoadhesive property of water-soluble β-cyclodextrin grafted with chitosan. Int J Biol Macromol 48:589–595

    Article  CAS  Google Scholar 

  • Savla R, Taratula O, Garbuzenko O, Minko T (2011) Tumor targeted quantum dot-mucin 1 aptamer-doxorubicin conjugate for imaging and treatment of cancer. J Control Release 153:16–22

    Article  CAS  Google Scholar 

  • Shen J-M, Xu L, Lu Y, Cao H-M, Xu Z-G, Chen T, Zhang H-X (2012) Chitosan-based luminescent/magnetic hybrid nanogels for insulin delivery, cell imaging, and antidiabetic research of dietary supplements. Int J Pharm 427:400–409

    Article  CAS  Google Scholar 

  • Shim G, Han S-E, Yu Y-H, Lee S, Lee HY, Kim K, Kwon IC, Park TG, Kim YB, Choi YS, Kim C-W, Oh Y-K (2011) Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug. J Control Release 155:60–66

    Article  CAS  Google Scholar 

  • Shu C, Huang B, Chen X, Wang Y, Li X, Ding L, Zhong W (2013) Facile synthesis and characterization of water soluble ZnSe/ZnS quantum dots for cellar imaging. Spectrochim Acta A 104:143–149

    Article  CAS  Google Scholar 

  • Strobl JS, Nikkhah M, Agah M (2010) Actions of the anti-cancer drug suberoylanilide hydroxamic acid (SAHA) on human breast cancer cytoarchitecture in silicon microstructures. Biomaterials 31:7043–7050

    Article  CAS  Google Scholar 

  • Suzuki T, Hisakawa S, Itoh Y, Suzuki N, Takahashi K, Kawahata M, Yamaguchi K, Nakagawa H, Miyata N (2007) Design, synthesis, and biological activity of folate receptor-targeted prodrugs of thiolate histone deacetylase inhibitors. Bioorg Med Chem Lett 17:4208–4212

    Article  CAS  Google Scholar 

  • Szpak A, Kania G, Skorka T, Tokarz W, Zapotoczny S, Nowakowska M (2013) Stable aqueous dispersion of superparamagnetic iron oxide nanoparticles protected by charged chitosan derivatives. J Nanopart Res 15:1372–1383

    Article  Google Scholar 

  • Thanh NTK, Green LAW (2010) Functionalisation of nanoparticles for biomedical applications. Nano Today 5:213–230

    Article  CAS  Google Scholar 

  • Thomas M, Rivault F, Tranoy-Opalinski I, Roche J, Gesson J-P, Papot S (2007) Synthesis and biological evaluation of the suberoylanilide hydroxamic acid (SAHA) β-glucuronide and β-galactoside for application in selective prodrug chemotherapy. Bioorg Med Chem Lett 17:983–986

    Article  CAS  Google Scholar 

  • Tomczak N, Jańczewski D, Han M, Vancso GJ (2009) Designer polymer–quantum dot architectures. Prog Polym Sci 34:393–430

    Article  CAS  Google Scholar 

  • Wadajkar AS, Bhavsar Z, Ko C-Y, Koppolu B, Cui W, Tang L, Nguyen KT (2012) Multifunctional particles for melanoma-targeted drug delivery. Acta Biomater 8:2996–3004

    Article  CAS  Google Scholar 

  • Wang Y, Chen L (2011) Quantum dots, lighting up the research and development of nanomedicine. Nanomed-Nanotech 7:385–402

    Article  CAS  Google Scholar 

  • Wei G, Yan M, Ma L, Zhang H (2012) The synthesis of highly water-dispersible and targeted CdS quantum dots and it is used for bioimaging by confocal microscopy. Spectrochim Acta A 85:288–292

    Article  CAS  Google Scholar 

  • Wu W, Aiello M, Zhou T, Berliner A, Banerjee P, Zhou S (2010) In-situ immobilization of quantum dots in polysaccharide-based nanogels for integration of optical pH-sensing, tumor cell imaging, and drug delivery. Biomaterials 31:3023–3031

    Article  CAS  Google Scholar 

  • Xiao J, Wu M, Kai G, Wang F, Cao H, Yu X (2011) ZnO-ZnS QDs interfacial heterostructure for drug and food delivery application: enhancement of the binding affinities of flavonoid aglycones to bovine serum albumin. Nanomed-Nanotechnol 7:850–858

    Article  CAS  Google Scholar 

  • Yuan Q, Hein S, Misra RDK (2010) New generation of chitosan-encapsulated ZnO quantum dots loaded with drug: synthesis, characterization and in vitro drug delivery response. Acta Biomater 6:2732–2739

    Article  CAS  Google Scholar 

  • Yukawa H, Kagami Y, Watanabe M, Oishi K, Miyamoto Y, Okamoto Y, Tokeshi M, Kaji N, Noguchi H, Ono K, Sawada M, Baba Y, Hamajima N, Hayashi S (2010) Quantum dots labeling using octa-arginine peptides for imaging of adipose tissue-derived stem cells. Biomaterials 31:4094–4103

    Article  CAS  Google Scholar 

  • Zhang X, Wu Z, Gao X, Shu S, Zhang H, Wang Z, Li C (2009) Chitosan bearing pendant cyclodextrin as a carrier for controlled protein release. Carbohyd Polym 77:394–401

    Article  CAS  Google Scholar 

  • Zhao M-X, Xia Q, Feng X-D, Zhu X-H, Mao Z-W, Ji L-N, Wang K (2010) Synthesis, biocompatibility and cell labeling of l-arginine-functional β-cyclodextrin-modified quantum dot probes. Biomaterials 31:4401–4408

    Article  CAS  Google Scholar 

  • Zhou L, Zhang F (2011) Thermo-sensitive and photoluminescent hydrogels: synthesis, characterization, and their drug-release property. Mat Sci Eng C 31:1429–1435

    Article  CAS  Google Scholar 

  • Zhou Y, Shi L, Li Q, Jiang H, Lv G, Zhao J, Wu C, Selke M, Wang X (2010) Imaging and inhibition of multi-drug resistance in cancer cells via specific association with negatively charged CdTe quantum dots. Biomaterials 31:4958–4963

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (No. 81173023), JiangSu Province of Top-level Talents (No. FJ10120), the Fundamental Research Funds for the Central Universities (No. JKY2011097), and the College Graduate Scientific Research and Innovation Program of JiangSu Province of China (No. CXZZ11-0814).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Li Ding or Wenying Zhong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shu, C., Li, R., Guo, J. et al. New generation of β-cyclodextrin-chitosan nanoparticles encapsulated quantum dots loaded with anticancer drug for tumor-target drug delivery and imaging of cancer cells. J Nanopart Res 15, 1927 (2013). https://doi.org/10.1007/s11051-013-1927-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-013-1927-4

Keywords

Navigation