Synthesis, physicochemical characterization and pharmaceutical function of niosomal nanoparticles-encapsulated bioactive compound for osteosarcoma treatment

Document Type : Research Paper


1 Depatment of Medical Biotechnology, Faculty of Medicine, Shahid Sadoughi University of Medical sciences, Yazd, Iran

2 Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Department of Medical Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Department of Mechanical Engineering, University of Tehran, Tehran, Iran

5 Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

6 Department of Advanced Technologies, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

7 Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran

8 Department of Psychology, University of New Mexico, Albuquerque, New Mexico, USA


Objective(s): The purpose of this study is to synthesizing and characterizing niosomes containing curcumin in order to delivery to bone cancer cells. Nano-carriers were synthesized using thin film method and curcumin was loaded into them by active hydration method.
Materials and Methods: The optimal formula was selected based on the encapsulation efficiency and release profile. Then the physicochemical properties of nanoparticles such as size and zeta potential, morphology and system-drug interaction were evaluated by using DLS, SEM, AFM and FTIR methods. Finally, the toxicity of nanosystems on bone cancer cell line MG-63 as resistant cells to treatment was examined by MTT assay. 
Results: Niosomes containing curcumin with size of 90.8 nm, PDI of 0.236, zeta potential of -8.9 and encapsulation rate of 73.5 ± 1.8 have slow-release profile. The maximum release rate of the drug for this nano-carrier in healthy and cancerous within 72 hr was 60.12% and 64.35% respectively. IR and morphological investigations showed no chemical interaction between curcumin and nanocarrier and the particles are spherical in shape. The results of the MTT assay also showed that by encapsulating curcumin, its effect on bone cancer cells increased and the resistance of MG-63 cells to treatment decreased. 
Conclusion: The results of this study showed that niosomes containing curcumin with appropriate physicochemical properties can improve the treatment process in bone cancer cells and also reduce the resistance of this cell to the drug and could be proposed as a new therapeutic strategy to help the treatment of osteosarcoma.


1.    Durfee RA, Mohammed M, Luu HH. Review of osteosarcoma and current management. Rheumatology and Ther. 2016;3(2):221-243.
2.    Harrison DJ, Geller DS, Gill JD, Lewis VO, Gorlick R. Current and future therapeutic approaches for osteosarcoma. Expert review of anticancer therapy. 2018;18(1):39-50.
3.    Czarnecka AM, Synoradzki K, Firlej W, Bartnik E, Sobczuk P, Fiedorowicz M, et al. Molecular biology of osteosarcoma. Cancers. 2020;12(8):2130.
4.    Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33(27):3029-3035.
5.    Simpson S, Dunning MD, de Brot S, Grau-Roma L, Mongan NP, Rutland CS. Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics. Acta Vet Scand. 2017; 59(1): 1-11.
6.    Smrke A, Anderson PM, Gulia A, Gennatas S, Huang PH, Jones RL. Future Directions in the Treatment of Osteosarcoma. Cells. 2021;10(1):172-183.
7.    Omidi M, Malakoutian M, Choolaei M, Oroojalian F, Haghiralsadat F, Yazdian F. A Label-Free detection of biomolecules using micromechanical biosensors. Chin Phys Lett. 2013;30(6):068701.
8.    Zhang Y, Yang J, Zhao N, Wang C, Kamar S, Zhou Y, et al. Progress in the chemotherapeutic treatment of osteosarcoma. Oncology letters. 2018;16(5):6228-6237.
9.    Li S, Sun W, Wang H, Zuo D, Hua Y, Cai Z. Research progress on the multidrug resistance mechanisms of osteosarcoma chemotherapy and reversal. Tumor Biol. 2015;36(3):1329-1338.
10.    Spínola V, Castilho PC. Evaluation of Asteraceae herbal extracts in the management of diabetes and obesity. Contribution of caffeoylquinic acids on the inhibition of digestive enzymes activity and formation of advanced glycation end-products (in vitro). Phytochemistry. 2017;143:29-35.
11.    Jiang Y, Peng T, Gaur U, Silva M, Little P, Chen Z, et al. Role of corticotropin releasing factor in the neuroimmune mechanisms of depression: Examination of current pharmaceutical and herbal therapies. Front Cell Neurosci. 2019; 13: 290-302. 2019;13:290.
12.    Sivaraman D, Anbu N, Kabilan N, Kumar MP, Shanmugapriya P, Christian G. Review on current treatment strategy in Alzheimer’s disease and role of herbs in treating neurological disorders. Int J Trans Res Ind Med. 2019;1(1):33-43.
13.    Mansoori B, Mohammadi A, Doustvandi MA, Mohammadnejad F, Kamari F, Gjerstorff MF, et al. Photodynamic therapy for cancer: Role of natural products. Photodiagnosis Photodyn Ther. 2019;26:395-404.
14.    Akhlaghi M, Ebrahimpour M, Ansari K, Parnian F, Zarezadeh Mehrizi M, Taebpour M. Synthesis, study and characterization of nano niosomal system containing Glycrrizha glabra extract in order to improve its therapeutic effects. New Cell Mol Biotech. 2021;11(42):65-82.
15.    Babazadeh A, Zeinali M, Hamishehkar H. Nano-phytosome: a developing platform for herbal anti-cancer agents in cancer therapy. Curr. Drug Targets. 2018;19(2):170-80.
16.    Hewlings SJ, Kalman DS. Curcumin: a review of its effects on human health. Foods. 2017;6(10):92.
17.    Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin: miniperspective. J Med Chem. 2017;60(5):1620-1637.
18.    Hussain Z, Thu HE, Amjad MW, Hussain F, Ahmed TA, Khan S. Exploring recent developments to improve antioxidant, anti-inflammatory and antimicrobial efficacy of curcumin: A review of new trends and future perspectives. Mater Sci Eng C. 2017;77:1316-1326.
19.    Fadus MC, Lau C, Bikhchandani J, Lynch HT. Curcumin: An age-old anti-inflammatory and anti-neoplastic agent. J Tradit Complement Med. 2017;7(3):339-346.
20.    da Silva AC, de Freitas Santos PD, do Prado Silva JT, Leimann FV, Bracht L, Goncalves OH. Impact of curcumin nanoformulation on its antimicrobial activity. Trends Food Sci Technol. 2018;72:74-82.
21.    Zhang W, Chen C, Shi H, Yang M, Liu Y, Ji P, et al. Curcumin is a biologically active copper chelator with antitumor activity. Phytomedicine. 2016;23(1):1-8.
22.    Rahmani AH, Alsahli MA, Aly SM, Khan MA, Aldebasi YH. Role of curcumin in disease prevention and treatment. Adv Biomed Res. 2018;7.
23.    Salehi B, Stojanović-Radić Z, Matejić J, Sharifi-Rad M, Kumar NVA, Martins N, et al. The therapeutic potential of curcumin: A review of clinical trials. Eur J Med Chem. 2019;163:527-545.
24.    Oroojalian F, Rezayan AH, Shier WT, Abnous K, Ramezani M. Megalin-targeted enhanced transfection efficiency in cultured human HK-2 renal tubular proximal cells using aminoglycoside-carboxyalkyl-polyethylenimine-containing nanoplexes. Int J Pharm. 2017;15(1):102-120
25.    Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res Pharm Sci. 2018;13(4):288-303. 
26.    Kadian R. Nanoparticles: A promising drug delivery approach. Asian J Pharm Clin Res. 2018:30-35.
27.    Rashidi A, Omidi M, Choolaei M, Nazarzadeh M, Yadegari A, Haghierosadat F, Oroojalian F, Azhdari M. Electromechanical properties of vertically aligned carbon nanotube. Adv Mat Res. 2013; 705: 332-336.
28.    Rahimizadeh M, Eshghi H, Shiri A, Ghadamyari Z, Matin MM, Oroojalian F, et al. Fe (HSO 4) 3 as an efficient catalyst for diazotization and diazo coupling reactions. J Korean Chem Soc. 2012;56(6):716-719.
29.    Akhlaghi M, Taebpour M, Lotfabadi NN, Naghib SM, Jalili N, Farahmand L, et al. Synthesis and characterization of smart stimuli-responsive herbal drug-encapsulated nanoniosome particles for efficient treatment of breast cancer. Nanotechnology Reviews. 2022;11(1):1364-1385.
30.    Mohseni M, Dehghani AM, Akhlaghi M, Ansari K. A New Therapeutic Approach For The Treatment Of Breast Cancer Using Synthesis Of Liposomes Scan Online To View This Article Containing Silybinin And Their Characterization. 2021.
31.    Hemati M, Haghiralsadat F, Jafary F, Moosavizadeh S, Moradi A. Targeting cell cycle protein in gastric cancer with CDC20siRNA and anticancer drugs (doxorubicin and quercetin) co-loaded cationic PEGylated nanoniosomes. Int J Nanomedicine. 2019;14:6575.
32.    Nia AH, Behnam B, Taghavi S, Oroojalian F, Eshghi H, Shier WT, Abnous K, Ramezani M. Evaluation of chemical modification effects on DNA plasmid transfection efficiency of single-walled carbon nanotube–succinate–polyethylenimine conjugates as non-viral gene carriers. Med Chem Comm. 2017;8(2):364-375.
33.    Roundhill EA, Jabri S, Burchill SA. ABCG1 and Pgp identify drug resistant, self-renewing osteosarcoma cells. Cancer Letters. 2019;1:142-157.
34.    Tang ML, Bai XJ, Li Y, Dai XJ, Yang F. MMP-1 over-expression promotes malignancy and stem-like properties of human osteosarcoma MG-63 cells in vitro. Curr. med. sci. 2018;38(5):809-817.
35.    Ferrari S, Smeland S, Mercuri M, Bertoni F, Longhi A, Ruggieri P, et al. Neoadjuvant chemotherapy with high-dose Ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: a joint study by the Italian and Scandinavian Sarcoma Groups. J Clin Oncol. 2005;23(34):8845-8852.
36.    Chen P, Wang H, Yang F, Chen H, He W, Wang J. Curcumin promotes osteosarcoma cell death by activating miR‐125a/ERRα signal pathway. J Cell Biochem. 2017;118(1):74-81.
37.    Zhang Y, Chen P, Hong H, Wang L, Zhou Y, Lang Y. JNK pathway mediates curcumin-induced apoptosis and autophagy in osteosarcoma MG63 cells. Exp Ther Med. 2017;14(1):593-599.
38.    Aziz MNM, Hussin Y, Che Rahim NF, Nordin N, Mohamad NE, Yeap SK, et al. Curcumin analog DK1 induces apoptosis in human osteosarcoma cells in vitro through mitochondria-dependent signaling pathway. Molecules. 2018;23(1):75.
39.    Yu D, An F, He X, Cao X. Curcumin inhibits the proliferation and invasion of human osteosarcoma cell line MG-63 by regulating miR-138. Int J Clin. 2015;8(11):14946.
40.    Luo Z, Li D, Luo X, Li L, Gu S, Yu L, et al. Curcumin may serve an anticancer role in human osteosarcoma cell line U-2 OS by targeting ITPR1. Oncology Letters. 2018;15(4):5593-5601.
41.    Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 1). Trop J Pharm Res. 2013;12(2):255-264.
42.    Danhier F, Feron O, Préat V. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148(2):135-146.
43.    Malekimusavi H, Ghaemi A, Masoudi G, Chogan F, Rashedi H, Yazdian F, et al. Graphene oxide‐l‐arginine nanogel: a pH‐sensitive fluorouracil nanocarrier. Biotechnol. Appl. Biochem. 2019;66(5):772-780.
44.    Ghafari M, Haghiralsadat F, Khanamani Falahati‐pour S, Zavar Reza J. Development of a novel liposomal nanoparticle formulation of cisplatin to breast cancer therapy. J Cell Biochem. 2020;121(7):3584-3592.
45.    Akhlaghi M, Taebpour M, Sharafaldini M, Javani O, Haghiralsadat BF, Oroojalian F, et al. Fabrication, characterization and evaluation of anti-cancer and antibacterial properties of nanosystems containing Hedera Helix aqueous extracts. Nanomed J. 2022; 9(1): 43-56. 
46.    Shehata TM, Ibrahim MM, Elsewedy HS. Curcumin Niosomes Prepared from Proniosomal Gels: In vitro Skin Permeability, Kinetic and In vivo Studies. Polymers. 2021;13(5):791.
47.    Azadmanesh F, Pourmadadi M, Zavar Reza J, Yazdian F, Omidi M, Haghirosadat BF. Synthesis of a novel nanocomposite containing chitosan as a three‐dimensional printed wound dressing technique: Emphasis on gene expression. Biotechnology Progress. 2021;37(4):3132-3145.
48.    Mirhosseini M, Shekari-Far A, Hakimian F, Haghiralsadat BF, Fatemi SK, Dashtestani F. Core-shell Au@ Co-Fe hybrid nanoparticles as peroxidase mimetic nanozyme for antibacterial application. Process Biochem. 2020;95:131-138.
49.    Haghiralsadat F, Amoabediny G, Naderinezhad S, Zandieh-Doulabi B, Forouzanfar T, Helder MN. Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance. Int J Nanomedicine. 2018;13:3853.