SPION Loaded Poly(L-lysine)/Hyaluronic Acid Micelles as MR Contrast Agent and Gene Delivery Vehicle for Cancer Theranostics

Reju George Thomas; Muthunarayanan Muthiah; MyeongJu Moon; In-Kyu Park; Yong Yeon Jeong

Macromolecular Research, Vol.25, No.5, 446-451, May, 2017

DOI10.1007/s13233-017-5053-5 Export Citation

SPION Loaded Poly(L-lysine)/Hyaluronic Acid Micelles as MR Contrast Agent and Gene Delivery Vehicle for Cancer Theranostics

Reju George Thomas¹, Muthunarayanan Muthiah^{2, 3}, MyeongJu Moon⁴, In-Kyu Park², and Yong Yeon Jeong^{1, †}

¹Department of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju 61469, Korea
²Department of Biomedical Science, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Korea
³Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA
⁴DKC corporation (BioActs), Incheon, South Korea

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In this work we evaluated the ability of a SPION (Superparamagnetic iron oxide nanoparticle) loaded micelle system to safely and efficiently transfer foreign DNA into cells with the help of poly(L-lysine) (PLL) as DNA-carrier. Average particle size of PLL coated hyaluronic acid (HA) loaded SPION (PLL-HA-SPION) micelle was approximately 200 nm in size with spherical morphology. PLL-HA-SPION micelle was found to be nontoxic to the NIH3T3 (murine fibroblast cells) and the in vitro uptake was also tested in CT-26 (murine colon cancer cells) by prussian blue staining. Agarose gel retardation study showed the efficient binding of PLL-HA-SPION micelle with plasmid DNA (pLuc). The formed PLL-HA-SPION/pLuc complex could be efficiently transfected into CT-26 cell line. Finally, MR imaging was also used to check uptake property of SPION loaded in PLL-HA-SPION/DNA complex in vitro. The result showed that the PLL-HA-SPION micelle can be applied to MR imagingguided gene therapy in vivo and it is also advantageous for using this system for the magnetic hyperthermia based cancer therapy.

Keywords:gene delivery;cancer;theranostics;PLL;hyaluronic acid

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[Referenced By]

[1] Zhu S, Lu H, Xiang J, Tang K, Zhang B, Zhou M, Tan C, Li G, Chin. Sci. Bull., 47, 654 (2002)

[2] Toole BP, Nat. Rev. Cancer, 4, 528 (2004)

[3] Zhou B, Weigel JA, Fauss L, Weigel PH, J. Biol. Chem., 275, 37733 (2000)

[4] Jung HS, Kong WH, Sung DK, Lee MY, Beack SE, Keum DH, Kim KS, Yun SH, Hahn SK, ACS. Nano, 8, 260 (2014)

[5] Choi KY, Min KH, Na JH, Choi K, Kim K, Park JH, Kwon IC, Jeong SY, J. Mater. Chem., 19, 4102 (2009)

[6] Boeriu CG, Springer J, Kooy FK, van den Broek LAM, EgginkInt G, J. Carbonydr. Chem., 2013, 1 (2013)

[7] Jing J, Alaimo D, De Vlieghere E, Jerome C, De Wever O, De Geest BG, Auzely-Velty R, J. Mater. Chem., 1, 3883 (2013)

[8] Liu Y, Sun J, Lian H, Li X, Cao W, Bai L, Wang Y, He Z, J. Chromatogr. B, 935, 10 (2013)

[9] Wei X, Senanayake TH, Warren G, Vinogradov SV, Bioconjugate Chem., 24, 658 (2013)

[10] Saravanakumar G, Deepagan VG, Jayakumar R, Park JH, J. Biomed. Nanotechnol., 10, 17 (2014)

[11] Anisha BS, Sankar D, Mohandas A, Chennazhi KP, Nair SV, Jayakumar R, Carbohydr. Polym., 92, 1470 (2013)

[12] Hiraki J, Ichikawa T, Ninomiya SI, Seki H, Uohama K, Seki H, Kimura S, Yanagimoto Y, Barnett JW, Regul. Toxicol. Pharmacol., 37, 328 (2003)

[13] Krikorian V, Kurian M, Calvin ME, Nowak AP, Deming TJ, Pochan DJ, J. Polym. Sci. B: Polym. Phys., 40(22), 2579 (2002)

[14] Sun SH, Zeng H, J. Am. Chem. Soc., 124(28), 8204 (2002)

[15] Mohammadi Z, Dorkoosh FA, Hosseinkhani S, Amini T, Rahimi AA, Najafabadi AR, Acta Pharmacol. Sin., 62, 83 (2012)

[16] Thomas RG, Moon M, Lee S, Jeong YY, Int. J. Biol. Macromol., 72, 510 (2015)

[17] Petersen SKS, Teske M, Minrath I, Schmitz KP, Sternberg K, E-J. Chem., 1, 11 (2013)

[18] Cho KY, Chung TW, Kim BC, Kim MK, Lee JH, Wee WR, Cho CS, Int. J. Pharm., 260, 83 (2003)

[19] Rozenberg M, Shoham G, Biophys. Chem., 125, 166 (2007)