Apoptosis-induced anticancer effect of transferrin-conjugated solid lipid nanoparticles of curcumin

Cancer Nanotechnology - Tập 3 Số 1-6 - Trang 65-81 - 2012
Rohit S. Mulik1,2,3, Jukka Mönkkönen2, Risto O. Juvonen4, Kakasaheb R. Mahadik3, Anant Paradkar5
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, USA
2Department of Biopharmacy, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
3Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth University, Pune, India
4Department of Toxicology, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
5Centre for Pharmaceutical Engineering Science, University of Bradford, Bradford, UK

Tóm tắt

AbstractBroad spectrum therapeutic potential of curcumin is usually hampered by its photodegradation and low bioavailability. Present investigation was designed with an objective to develop transferrin-mediated solid lipid nanoparticles (Tf-C-SLN) resistant to the photostability and capable of enhancing the bioavailability by targeted drug delivery to elicit anticancer activity against SH-SY5Y neuroblastoma cells in vitro. Hot homogenization method was used for the formulation of Tf-C-SLN and evaluated physicochemically using parameters such as, size, zeta potential, entrapment efficiency and photostability, transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), differential scanning colorimetry (DSC), and in vitro release study. In vitro cytotoxicity and apoptosis investigations were performed using microplate analysis and flow cytometry techniques. The physicochemical characterization confirmed the suitability of formulation method and various parameters therein. TEM investigation revealed the spherical morphology while NMR and DSC study confirmed the entrapment of curcumin inside the nanoparticles. The cytotoxicity, reactive oxygen species, and cell uptake were found to be increased considerably with Tf-C-SLN compared with curcumin-solubilized surfactant solution, and curcumin-loaded SLN (C-SLN) suggesting the targeting effect. AnnexinV-FITC/PI double staining, DNA analysis, caspase detection, and reduced mitochondrial potential confirmed the induction of apoptosis with nanoparticle treatment. Enhanced anticancer activity with Tf-C-SLN compared with curcumin-solubilized surfactant solution and C-SLN was observed from flow cytometry investigations with apoptosis being the major underlying mechanism. The in vitro observations of our investigation are very compelling and concrete to advocate the potential of Tf-C-SLN in enhancing the anticancer effect of curcumin against neuroblastoma in vivo and possible clinical applications.

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Tài liệu tham khảo

Adrian JE, Wolf A, Steinbach A, Rössler J, Süss R (2011) Targeted delivery to neuroblastoma of novel siRNA-anti-GD2-liposomes prepared by dual asymmetric centrifugation and sterol-based post-insertion method. Pharm Res 28(9):2261–2272

Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune, and neoplastic diseases. Int J Biochem Cell Biol 41:40–59

Aggarwal BB, Kumar A, Bharti A (2003a) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23:363–398

Aggarwal B, Swaroop P, Protiva P, Raj SV, Shirin H, Holt PR (2003b) Cox-2 is needed but not sufficient for apoptosis induced by Cox-selective inhibitors in colon cancer cells. Apoptosis 8:649–654

Aggarwal BB, Kumar A, Aggarwal MS, Shishodia S (2005a) Curcumin derived from turmeric (Curcuma longa): a spice for all seasons. In: Preuss HG (ed) Phytopharmaceuticals in cancer chemoprevention. CRC, Boca Raton, pp 349–387

Aggarwal BB, Shishodia S, Takada Y (2005b) Curcumin suppresses the paclitaxel-induced nuclear factor-{kappa}B pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res 11:7490–7498

Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818

Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB (2008) Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett 267:133–164

Ansari MJ, Ahmad S, Kohli K, Ali J, Khar RK (2005) Stability indicating HPTLC determination of curcumin in bulk drug and pharmaceutical formulations. J Pharm Biomed Anal 39:132–138

Azuine MA, Bhide SV (1992) Chemopreventive effect of turmeric against stomach and skin tumors induced by chemical carcinogens in Swiss mice. Nutr Cancer 17:77–83

Bong PH (2000) Spectral and photophysical behaviors of curcumin and curcuminoids. Bull Korean Chem Soc 21(1):81–86

Bradford MA (1976) Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

Buttke TM, Sandstrom PM (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15:7–10

Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee RK (2004) Turmeric and curcumin: biological actions and medicinal applications. Curr Sci 87:44–53

Chearwae W, Anuchapreeda S, Nandigama K, Ambudkar SV, Limtrakul P (2004) Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II, and III purified from turmeric powder. Biochem Pharmacol 68:2043–2052

Chearwae W, Wu CP, Chu HY, Lee TR, Ambudkar SV, Limtrakul P (2006) Curcuminoids purified from turmeric powder modulate the function of human multidrug resistance protein 1 (ABCC1). Cancer Chemother Pharmacol 57:376–388

Christine SA, Kumari L, Khar A (2004) Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Mol Cancer Ther 3:1101–1108

Dehal PK, Embleton MJ, Kemshead JT, Hawkins RE (2002) Targeted cytokine delivery to neuroblastoma. Biochem Soc Trans 30(4):518–520

Di Paolo D et al (2011) Neuroblastoma-targeted nanoparticles entrapping siRNA specifically knockdown ALK. Mol Ther 19(6):1131–1140

Dilnawaz F, Singh A, Sahoo SK (2012) Transferrin-conjugated curcumin-loaded superparamagnetic iron oxide nanoparticles induce augmented cellular uptake and apoptosis in K562 cells. Acta Biomater 8:704–719

Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE (2001) Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate 47:293–303

Ganta S, Amiji M (2009) Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Mol Pharm 6:928–939

Gupta Y, Jain A, Jain SK (2007) Transferrin-conjugated solid lipid nanoparticles for enhanced delivery of quinine dihydrochloride to the brain. J Pharm Pharmacol 59:935–940

Gutman RL, Peacock G, Lu R (2000) Targeted drug delivery for brain cancer treatment. J Control Release 65:31–41

Jacobson MD (1996) Reactive oxygen species and programmed cell death. Trends Biochem Sci 21:83–86

Jenning V, Korting MS, Gohla S (2000) Vitamin A-loaded solid lipid nanoparticles for topical use: drug release properties. J Control Release 66:115–126

Joe B, Vijaykumar M, Lokesh BR (2004) Biological properties of curcumin-cellular and molecular mechanisms of action. Crit Rev Food Sci Nutr 44:97–111

Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini KI (2008) Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochem Biophys Acta 1780:673–679

Lemieux P, Page M (1994) Sensitivity of multidrug-resistant MCF-7 cells to a transferrin-doxorubicin conjugate. Anticancer Res 14:397–403

Li JL, Wanga L, Liu XY (2009) In vitro cancer cell imaging and therapy using transferrin-conjugated gold nanoparticles. Cancer Lett 274:319–326

Martell LA, Agrawal A, Ross DA, Muraszko KM (1993) Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors. Cancer Res 53(6):1348–1353

Maruyama K, Ishida O, Kasaoka S (2004) Intracellular targeting of sodium mercaptoundecahydrododecaborate (BSH) to solid tumors by transferrin-PEG liposomes, for boron neutron-capture therapy (BNCT). J Control Release 98:195–207

Mulik R, Mahadik KR, Paradkar AR (2009) Development of curcuminoids loaded poly(butyl) cyanoacrylate nanoparticles: physicochemical characterization and stability study. Eur J Pharm Sci 37:395–404

Mulik RS, Mönkkönen J, Juvonen RO, Mahadik KR, Paradkar AR (2010) Transferrin mediated solid lipid nanoparticles containing curcumin: enhanced in vitro anticancer activity by induction of apoptosis. Int J Pharm 398:190–203

Padamwar MN, Pokharkar VB (2006) Development of vitamin loaded topical liposomal formulation using factorial design approach: drug deposition and stability. Int J Pharm 320:37–44

Page-Clisson ME, Pinto HA, Ourevitch M, Andremont A, Couvreur P (1998) Development of ciprofloxacin-loaded nanoparticles: physicochemical study of the drug carrier. J Control Release 56:23–32

Qian ZM, Li H, Sun H, Ho K (2002) Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol Rev 54:561–587

Ramachandran C, Fonseca HB, Jhabvala P, Escalon EA, Melnick SJ (2002) Curcumin inhibits telomerase activity through human telomerase reverse transcriptase in MCF-7 breast cancer cell line. Cancer Lett 184:1–6

Reddy LH, Murthy RSR (2004) Influence of polymerization technique and experimental variables on the particle properties and release kinetics of methotrexate from poly(butylcyanoacrylate) nanoparticles. Acta Pharma 54:103–118

Sahoo SK, Labhasetwar V (2005) Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention. Mol Pharm 2:373–383

Sharma RA, Gescher AJ, Steward WP (2005) Curcumin: the story so far. Eur J Cancer 41:1955–1968

Singh S, Aggarwal BB (1995) Activation of transcription factor NF-kB is suppressed by curcumin (diferulolylmethane). J Biol Chem 270:24995–25000

Skommer J, Wlodkowic D, Pelkonen J (2006) Cellular foundation of curcumin-induced apoptosis in follicular lymphoma cell lines. Exp Hematol 34:463–474

Thangapazham RL, Sharma A, Maheshwari RK (2006) Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J 8:E443–E449

Tivnan A, Orr WS, Gubala V, Nooney R, Williams DE (2012) Inhibition of Neuroblastoma tumor growth by targeted delivery of MicroRNA-34a using anti-disialoganglioside GD2 coated nanoparticles. PLoS One 7(5):e38129

Tiyaboonchaia W, Tungpradita W, Plianbangchang P (2007) Formulation and characterization of curcuminoids loaded solid lipid nanoparticles. Int J Pharm 337:299–306

Ulbrich K, Hekmatara T, Herbert E, Kreuter J (2009) Transferrin and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood–brain barrier (BBB). Eur J Pharm Biopharm 71:251–256

Veldhoen S, Laufer SD, Restle T (2008) Recent developments in peptide-based nucleic acid delivery. Int J Mol Sci 9:1276–1320

Vermes I, Haanen C, Reutelingsperger C (2000) Flow cytometry of apoptotic cell death. J Immuno Methods 243:167–190

Wang H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27:612–616

Wang F, Jiang X, Yang DC, Elliott RL, Head JF (2000) Doxorubicin-gallium-transferrin conjugate overcomes multidrug resistance: evidence for drug accumulation in the nucleus of drug resistant MCF-7/ADR cells. Anticancer Res 20:799–808

Weir NM, Selvendiran K, Kutala VK (2007) Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biol Ther 6:178–184

Widera A, Norouziyan F, Shen WC (2003) Mechanisms of Tfr-mediated transcytosis and sorting in epithelial cells and applications toward drug delivery. Adv Drug Deliv Rev 55:1439–1466

Yang X, Koh CG, Liu S (2009) Transferrin receptor-targeted lipid nanoparticles for delivery of an antisense oligodeoxyribonucleotide against bcl-2. Mol Pharm 6:221–230