Evaluation of protein corona formation and anticancer efficiency of curcumin-loaded zwitterionic silica nanoparticles

Document Type: Research Paper


Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran


Objective(s): Study and development of antifouling nanosystem for conjugation of drugs were attracting great attention in recent years. The present study aimed to develop novel curcumin-loaded silica nanoparticles containing zwitterionic coating as an antifouling system to provide protein corona free nanoformulations for curcumin.
Materials and Methods: Silica nanoparticles were prepared using the Stöber method, and mono- and bi-functionalized nanoparticles were obtained by modifying the surface of the bare silica nanoparticles with (3-aminopropyl)triethoxysilane (APTES), polyethylene glycol amine, APTES with sulfobetaine, and polyethylene glycol amine with sulfobetaine. Nanoparticle characterization, curcumin release, and measurement of protein corona inhibition were performed after incubation in the human plasma and MTT assay to confirm the stability and efficiency of the nanoparticles.
Results: The presence of the sulfobetaine group could influence the curcumin loading capacity of the silica nanoparticles. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated no significant protein adsorption on the curcumin-loaded, zwitterionic-coated nanoparticles compared to the other nanoparticles. In addition, the MTT assay confirmed the cytotoxicity of the curcumin-loaded sulfobetaine-APTES-silica nanoparticles on MCF-7 cancer cells.
Conclusion: Our findings confirmed the effects of the zwitterionic coating on the physicochemical properties of the nanoparticles. These findings play a key role in the development of novel nanoparticles for drug delivery applications.


1.Falconieri M, Adamo M, Monasterolo C, Bergonzi M, Coronnello M, Bilia A. New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility. Planta Med. 2016; 22; 83(05): 420–425.
2.Gomes CA, Girão da Cruz T, Andrade JL, Milhazes N, Borges F, Marques MPM. Anticancer Activity of Phenolic Acids of Natural or Synthetic Origin: A Structure−Activity Study. J Med Chem. 2003; 46(25): 5395–5401.
3.Chakraborti S, Dhar G, Dwivedi V, Das A, Poddar A, Chakraborti G, Basu G, Chakrabarti P, Surolia A, Bhattacharyya B. Stable and Potent Analogues Derived from the Modification of the Dicarbonyl Moiety of Curcumin. Biochemistry. 2013; 52(42): 7449–7460.
4.Yang X, Li Z, Wang N, Li L, Song L, He T, Sun L, Wang Z, Wu Q, Luo N, Yi C. Curcumin-Encapsulated Polymeric Micelles Suppress the Development of Colon Cancer In Vitro and In Vivo. Sci Rep. 2015; 5(1): 10322.
5.Siviero A, Gallo E, Maggini V, Gori L, Mugelli A, Firenzuoli F, Vannacci A. Curcumin, a golden spice with a low bioavailability. Journal of Herbal Medicine. 2015; 5(2): 57–70.
6.Hsu C-H, Cheng A-L. CLINICAL STUDIES WITH CURCUMIN. In: Aggarwal BB, Surh Y-J, Shishodia S, editors. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease Boston, MA: Springer US; 2007, p. 471–480. Available from: http://link.springer.com/10.1007/978-0-387-46401-5_21
7.Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of Curcumin: Problems and Promises. Mol Pharmaceutics. 2007; 4(6): 807–818.
8.Thu Huong LT, Nam NH, Doan DH, My Nhung HT, Quang BT, Nam PH, Thong P.Q, Phuc N.X, Thu H.P. Folate attached, curcumin loaded Fe3O4 nanoparticles: A novel multifunctional drug delivery system for cancer treatment. Materials Chemistry and Physics. 2016; 172: 98–104.
9.Magro M, Campos R, Baratella D, Lima G, Holà K, Divoky C, Stollberger R, Malina O, Aparicio C, Zoppellaro G, Zbořil R. A Magnetically Drivable Nanovehicle for Curcumin with Antioxidant Capacity and MRI Relaxation Properties. Chem Eur J. 2014; 20(37): 11913–11920.
10.Manju S, Sharma CP, Sreenivasan K. Targeted coadministration of sparingly soluble paclitaxel and curcumin into cancer cells by surface engineered magnetic nanoparticles. J Mater Chem. 2011; 21(39): 15708.
11.Yallapu MM, Ebeling MC, Khan S, Sundram V, Chauhan N, Gupta BK, Puumala SE, Jaggi M, Chauhan SC. Novel Curcumin-Loaded Magnetic Nanoparticles for Pancreatic Cancer Treatment. Molecular Cancer Therapeutics. 2013; 12(8): 1471–1480.
12.Nh G, Li J. Targeted Theranostic Approach for Glioma Using Dendrimer-Based Curcumin Nanoparticle. J Nanomed Nanotechnol. 2016; 7(4). https://www.omicsonline.org/open-access/targeted-theranostic-approach-for-glioma-using-dendrimerbasedcurcumin-nanoparticle-2157-7439-1000393.php?aid=77685
13.Pillai JJ, Thulasidasan AKT, Anto RJ, Devika NC, Ashwanikumar N, Kumar GSV. Curcumin entrapped folic acid conjugated PLGA–PEG nanoparticles exhibit enhanced anticancer activity by site specific delivery. RSC Adv. 2015; 5(32): 25518–25524.
14.Salem M, Xia Y, Allan A, Rohani S, Gillies ER. Curcumin-loaded, folic acid-functionalized magnetite particles for targeted drug delivery. RSC Adv. 2015; 5(47): 37521–37532.
15.Lynch I, Dawson KA. Protein-nanoparticle interactions. Nano Today. 2008; 3(1–2): 40–47.
16.Salvati A, Pitek AS, Monopoli MP, Prapainop K, Bombelli FB, Hristov DR, Kelly PM, Åberg C, Mahon E, Dawson KA. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nature Nanotech. 2013; 8(2): 137–143.
17.Efremova NV, Sheth SR, Leckband DE. Protein-Induced Changes in Poly(ethylene glycol) Brushes: Molecular Weight and Temperature Dependence. Langmuir. 2001 ; 17(24): 7628–7636.
18.Kim HR, Andrieux K, Delomenie C, Chacun H, Appel M, Desmaële D, Taran F, Georgin D, Couvreur P, Taverna M. Analysis of plasma protein adsorption onto PEGylated nanoparticles by complementary methods: 2-DE, CE and Protein Lab-on-chip® system. Electrophoresis. 2007; 28(13): 2252–2261.
19.Pozzi D, Colapicchioni V, Caracciolo G, Piovesana S, Capriotti AL, Palchetti S, De Grossi S, Riccioli A, Amenitsch H, Laganà A. Effect of polyethyleneglycol (PEG) chain length on the bio–nano-interactions between PEGylated lipid nanoparticles and biological fluids: from nanostructure to uptake in cancer cells. Nanoscale. 2014; 6(5): 2782.
20.Estephan ZG, Schlenoff PS, Schlenoff JB. Zwitteration As an Alternative to PEGylation. Langmuir. 2011; 27(11): 6794–6800.
21.Estephan ZG, Jaber JA, Schlenoff JB. Zwitterion-Stabilized Silica Nanoparticles: Toward Nonstick Nano. Langmuir. 2010; 26(22): 16884–16889.
22.Safavi-Sohi R, Maghari S, Raoufi M, Jalali SA, Hajipour MJ, Ghassempour A, Mahmoudi M. Bypassing Protein Corona Issue on Active Targeting: Zwitterionic Coatings Dictate Specific Interactions of Targeting Moieties and Cell Receptors. ACS Appl Mater Interfaces. 2016; 8(35): 22808–22818.
23.Huang J, Xu W. Zwitterionic monomer graft copolymerization onto polyurethane surface through a PEG spacer. Applied Surface Science. 2010; 256(12): 3921–3927.
24.Liu J, Xu T, Gong M, Yu F, Fu Y. Fundamental studies of novel inorganic–organic charged zwitterionic hybrids. Journal of Membrane Science. 2006; 283(1–2): 190–200.
25.Xie M, Shi H, Ma K, Shen H, Li B, Shen S, Wang X, Jin Y. Hybrid nanoparticles for drug delivery and bioimaging: Mesoporous silica nanoparticles functionalized with carboxyl groups and a near-infrared fluorescent dye. Journal of Colloid and Interface Science. 2013; 395: 306–314.
26.Wu X, Wu M, Zhao JX. Recent development of silica nanoparticles as delivery vectors for cancer imaging and therapy. Nanomedicine: Nanotechnology, Biology and Medicine. 2014; 10(2): 297–312.
27.He Q, Shi J. Mesoporous silica nanoparticle based nano drug delivery systems: synthesis, controlled drug release and delivery, pharmacokinetics and biocompatibility. J Mater Chem. 2011; 21(16): 5845.
28.Kurniawan A, Gunawan F, Nugraha AT, Ismadji S, Wang M-J. Biocompatibility and drug release behavior of curcumin conjugated gold nanoparticles from aminosilane-functionalized electrospun poly( N -vinyl-2-pyrrolidone) fibers. International Journal of Pharmaceutics. 2017; 516(1–2): 158–169.
29.Kotcherlakota R, Barui AK, Prashar S, Fajardo M, Briones D, Rodríguez-Diéguez A, Patra CR, Gómez-Ruiz S. Curcumin loaded mesoporous silica: an effective drug delivery system for cancer treatment. Biomater Sci. 2016; 4(3): 448–459.
30.Stöber W, Fink A, Bohn E. Controlled growth of monodisperse silica spheres in the micron size range. Journal of Colloid and Interface Science. 1968; 26(1): 62–69.
31.Kong Z-L, Kuo H-P, Johnson A, Wu L-C, Chang KLB. Curcumin-Loaded Mesoporous Silica Nanoparticles Markedly Enhanced Cytotoxicity in Hepatocellular Carcinoma Cells. IJMS. 2019; 20(12): 2918.