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Mannan-Modified Solid Lipid Nanoparticles for Targeted Gene Delivery to Alveolar Macrophages

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ABSTRACT

Purpose

Cationic solid lipid nanoparticles (SLN) have established themselves during the past decades. They can efficiently bind DNA directly via ionic interaction and mediate gene transfection. One major problem with SLN is the lack of cell-targeting ability. In the present study, a mannan-based PE-grafted ligand was synthesized and used for the surface modification of DNA-loaded cationic SLN to prepare Man-SLN-DNA.

Methods

For in vitro test, the cytotoxicity and transfection investigation was carried out on murine macrophage cell line RAW 264.7. For in vivo evaluation, Man-SLN-DNA was delivered into the lung of the rats, and the alveolar macrophages (AM) were isolated for the fluorescence determination of transfection efficiency.

Results

When compared with non-modified SLN-DNA and Lipofectamine 2000-DNA, Man-SLN-DNA produced the highest gene expressions, especially in vivo.

Conclusion

These results demonstrated the active targeting ability of this kind of mannan-modified DNA-loaded vehicles, which may have great potential for targeted gene delivery.

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REFERENCES

  1. Jemal A, Thun MJ, Ries LA, Howe HL, Weir HK, Center MM et al. Annual report to the nation on the status of cancer, 1975–2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst. 2008;100:1672–94.

    Article  PubMed  Google Scholar 

  2. Tseng CL, Wu SY, Wang WH, Peng CL, Lin FH, Lin CC et al. Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer. Biomaterials. 2008;29:3014–22.

    Article  PubMed  CAS  Google Scholar 

  3. Wijagkanalan W, Kawakami S, Takenaga M, Igarashi R, Yamashita F, Hashida M. Efficient targeting to alveolar macrophages by intratracheal administration of mannosylated liposomes in rats. J Control Release. 2008;125:121–30.

    Article  PubMed  CAS  Google Scholar 

  4. Murer B. Targeted therapy in non-small cell lung cancer a commentary. Arch Pathol Lab Med. 2008;132:1573–5.

    PubMed  Google Scholar 

  5. Morille M, Passirani C, Vonarbourg A, Clavreul A, Benoit JP. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials. 2008;29:3477–96.

    Article  PubMed  CAS  Google Scholar 

  6. Rolland A. Gene medicines: the end of the beginning? Adv Drug Deliv Rev. 2005;57:669–73.

    Article  PubMed  CAS  Google Scholar 

  7. Zhao XB, Lee RJ. Tumor-selective targeted delivery of genes and antisense oligodeoxyribonucleotides via the folate receptor. Adv Drug Deliv Rev. 2004;56:1193–204.

    Article  PubMed  CAS  Google Scholar 

  8. Lee MK, Lim SJ, Kim CK. Preparation, characterization and in vitro cytotoxicity of paclitaxel-loaded sterically stabilized solid lipid nanoparticles. Biomaterials. 2007;28:2137–46.

    Article  PubMed  CAS  Google Scholar 

  9. Zhang HW, Bei JZ, Wang SG. Multi-morphological biodegradable PLGE nanoparticles and their drug release behavior. Biomaterials. 2009;30:100–7.

    Article  PubMed  CAS  Google Scholar 

  10. Karathanasis E, Chan L, Balusu SR, D’Orsi CJ, Annapragada AV, Sechopoulos I et al. Multifunctional nanocarriers for mammographic quantification of tumor dosing and prognosis of breast cancer therapy. Biomaterials. 2008;29:4815–22.

    Article  PubMed  CAS  Google Scholar 

  11. Yu W, Liu C, Ye J, Zou W, Zhang N, Xu W. Novel cationic SLN containing a synthesized single-tailed lipid as a modifier for gene delivery. Nanotechnology. 2009;20:215102.

    Article  PubMed  CAS  Google Scholar 

  12. Ye J, Wang A, Liu C, Chen Z, Zhang N. Anionic solid lipid nanoparticles supported on protamine/DNA complexes. Nanotechnology. 2008;19:285708.

    Article  CAS  Google Scholar 

  13. Zou W, Liu C, Chen Z, Zhang N. Studies on bioadhesive PLGA nanoparticles: a promising gene delivery system for efficient gene therapy to lung cancer. Int J Pharm. 2009;370:187–95.

    Article  PubMed  CAS  Google Scholar 

  14. Yu W, Zhang N. Surface modification of nanocarriers for cancer therapy. Curr Nanosci. 2009;5:123–34.

    Article  CAS  Google Scholar 

  15. Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J. 2007;9:E128–47.

    Article  PubMed  CAS  Google Scholar 

  16. van Vlerken LE, Vyas TK, Amiji MM. Poly(ethylene glycol)-modified nanocarriers for tumor-targeted and intracellular delivery. Pharm Res. 2007;24:1405–14.

    Article  PubMed  CAS  Google Scholar 

  17. Beduneau A, Saulnier P, Benoit JP. Active targeting of brain tumors using nanocarriers. Biomaterials. 2007;28:4947–67.

    Article  PubMed  CAS  Google Scholar 

  18. Wijagkanalan W, Kawakami S, Takenaga M, Igarashi R, Yamashita F, Hashida M. Efficient targeting to alveolar macrophages by intratracheal administration of mannosylated liposomes in rats. J Control Release. 2008;125:121–30.

    Article  PubMed  CAS  Google Scholar 

  19. Kawakami S, Higuchi Y, Hashida M. Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide. J Pharm Sci. 2008;97:726–45.

    Article  PubMed  CAS  Google Scholar 

  20. Mantovani A, Schioppa T, Porta C, Allavena P, Sica A. Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 2006;25:315–22.

    Article  PubMed  Google Scholar 

  21. Sica A, Schioppa T, Mantovani A, Allavena P. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42:717–27.

    Article  PubMed  CAS  Google Scholar 

  22. Ezekowitz RA, Williams DJ, Koziel H, Armstrong MY, Warner A, Richards FF et al. Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor. Nature. 1991;351:155–8.

    Article  PubMed  CAS  Google Scholar 

  23. Cui ZR, Hsu CH, Mumper RJ. Physical characterization and macrophage cell uptake of mannan-coated nanoparticles. Drug Dev Ind Pharm. 2003;29:689–700.

    Article  PubMed  CAS  Google Scholar 

  24. Cui ZG, Han SJ, Huang L. Coating of mannan on LPD particles containing HPV E7 peptide significantly enhances immunity against HPV-positive tumor. Pharm Res. 2004;21:1018–25.

    Article  PubMed  CAS  Google Scholar 

  25. Hattori Y, Kawakami S, Suzuki S, Yamashita F, Hashida M. Enhancement of immune responses by DNA vaccination through targeted gene delivery using mannosylated cationic liposome formulations following intravenous administration in mice. Biochem Biophys Res Commun. 2004;317:992–9.

    Article  PubMed  CAS  Google Scholar 

  26. Kaur A, Jain S, Tiwary AK. Mannan-coated gelatin nanoparticles for sustained and targeted delivery of didanosine: in vitro and in vivo evaluation. Acta Pharm. 2008;58:61–74.

    Article  PubMed  CAS  Google Scholar 

  27. Azarmi S, Roa WH, Loebenberg R. Targeted delivery of nanoparticles for the treatment of lung diseases. Adv Drug Deliv Rev. 2008;60:863–75.

    Article  PubMed  CAS  Google Scholar 

  28. Yu W, Zhang N, Li C. Saccharide modified pharmaceutical nanocarriers for targeted drug and gene delivery. Curr Pharm Des. 2009;15:3826–36.

    Article  PubMed  CAS  Google Scholar 

  29. Kawakami S, Wong J, Sato A, Hattori Y, Yamashita F, Hashida M. Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice. Biochim Biophys Acta Gen Subj. 2000;1524:258–65.

    Article  CAS  Google Scholar 

  30. Yang L, Cheng L, Wei Y, Tian L. Synthesis of N-[2-(cholesteryloxycarbonylamino) ethyl] carbamoylmethylated mannan. Sichuan Da Xue Xue Bao Yi Xue Ban. 2003;34:730–2.

    PubMed  CAS  Google Scholar 

  31. Vyas SP, Sihorkar V, Jain S. Mannosylated liposomes for bio-film targeting. Int J Pharm. 2007;330:6–13.

    Article  PubMed  CAS  Google Scholar 

  32. Cui Z, Mumper RJ. Topical immunization using nanoengineered genetic vaccines. J Control Release. 2002;81:173–84.

    Article  PubMed  CAS  Google Scholar 

  33. Tabatt K, Sameti M, Olbrich C, Muller RH, Lehr CM. Effect of cationic lipid and matrix lipid composition on solid lipid nanoparticle-mediated gene transfer. Eur J Pharm Biopharm. 2004;57:155–62.

    Article  PubMed  CAS  Google Scholar 

  34. Managit C, Kawakami S, Yamashita F, Hashida M. Effect of galactose density on asialoglycoprotein receptor-mediated uptake of galactosylated liposomes. J Pharm Sci. 2005;94:2266–75.

    Article  PubMed  CAS  Google Scholar 

  35. Yeeprae W, Kawakami S, Yamashita F, Hashida M. Effect of mannose density on mannose receptor-mediated cellular uptake of mannosylated O/W emulsions by macrophages. J Control Release. 2006;114:193–201.

    Article  PubMed  CAS  Google Scholar 

  36. Monsigny M, Quetard C, Bourgerie S, Delay D, Pichon C, Midoux P et al. Glycotargeting: the preparation of glyco-amino acids and derivatives from unprotected reducing sugars. Biochimie. 1998;80:99–108.

    Article  PubMed  CAS  Google Scholar 

  37. Barre A, Bourne Y, Van Damme EJ, Peumans WJ, Rouge P. Mannose-binding plant lectins: different structural scaffolds for a common sugar-recognition process. Biochimie. 2001;83:645–51.

    Article  PubMed  CAS  Google Scholar 

  38. Shibata K, Kudo Y, Tsunoda M, Hosokawa M, Sakai Y, Kotani M et al. Magnetometric evaluation of the effects of man-made mineral fibers on the function of macrophages using the macrophage cell line RAW 264.7. Ind Health. 2007;45:426–36.

    Article  PubMed  Google Scholar 

  39. Kabanov AV. Polymer genomics: an insight into pharmacology and toxicology of nanomedicines. Adv Drug Deliv Rev. 2006;58:1597–621.

    Article  PubMed  CAS  Google Scholar 

  40. Vega-Villa KR, Takemoto JK, Yanez JA, Remsberg CM, Forrest ML, Davies NM. Clinical toxicities of nanocarrier systems. Adv Drug Deliv Rev. 2008;60:929–38.

    Article  PubMed  CAS  Google Scholar 

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ACKNOWLEDGMENTS

The authors gratefully acknowledge Dr. Laird Forrest (The Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, USA) for language editing. The authors thank Mr. Tianliang Sun (Shanghai Institute for Biological Sciences, China) and Mr. Qiangjun Sui (Institute of Immunopharmacology and Immunotherapy, Shandong University, China) for the flow cytometry. The work was supported by Program for New Century Excellent Talents in University (NCET-08-0334), and the National Natural Science Foundation of China, No. 30572267.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Shandong University, 44 Wen Hua Xi Road, Ji’nan, 250012, Shandong Province, People’s Republic of China

    Wangyang Yu, Chunxi Liu, Yu Liu, Na Zhang & Wenfang Xu

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  1. Wangyang Yu
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  2. Chunxi Liu
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  3. Yu Liu
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Correspondence to Na Zhang.

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Yu, W., Liu, C., Liu, Y. et al. Mannan-Modified Solid Lipid Nanoparticles for Targeted Gene Delivery to Alveolar Macrophages. Pharm Res 27, 1584–1596 (2010). https://doi.org/10.1007/s11095-010-0149-z

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  • DOI: https://doi.org/10.1007/s11095-010-0149-z

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