Improved anticancer efficiency of Mitoxantrone by Curcumin loaded PLGA nanoparticles targeted with AS1411 aptamer

Document Type : Research Paper

Authors

1 Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4 Molecular and Cell biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

5 Department of Immunology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran

6 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Mitoxantrone (MTX) is one of the most commonly used chemotherapeutic agents for treatment of different cancers. However, prolonged treatment with MTX results in unwanted side effects and drug resistant cancer cells. Combination therapies and exploiting of targeted nanoparticles have the potential of improving the efficiency of drug treatment as well as reducing the side effects. Curcumin (CUR) is a biological molecules with anticancer property. In this study, we investigated whether targeted PLGA (Poly Lactic-co-Glycolic Acid)–CUR nanoparticles (NPs) can reinforce the effect of MTX on breast cancer cells.
Materials and Methods: PLGA NPs containing CUR targeted with AS1411 aptamer were prepared by single emulsion evaporation method. Physicochemical properties of NPs were investigated. The cytotoxicity of non-targeted and targeted NPs along with MTX was evaluated on MCF7, 4T1 and L929 cell lines.
Results: The results showed that PLGA-CUR NPs were synthetized with an average encapsulation efficiency of 66% with a mean size of 186±3.2 nm. The drug release of curcumin from these NPs within 72h was about 59% in neutral medium and 90% in acidic medium. Interestingly, the combined treatment with PLGA-CUR-Apt and MTX inhibited the cancer cell's proliferation significantly more than the non-targeted nanoparticles, CUR and MTX-treated group alone.
Conclusion: These results suggest that targeted PLGA-CUR nanoparticles may consider as a potential therapeutic contender in improving the efficacy of MTX in Breast cancer therapy.

Keywords


1.Ahmadpour S, Hosseinimehr SJ. Recent developments in peptide-based SPECT radiopharmaceuticals for breast tumor targeting. Life Sci. 2019; 239: 116870.
2.Nagpal M, Sood S. Role of curcumin in systemic and oral health: An overview. J Nat Sci Biol Med. 2013; 4(1): 3-7.
3.Sa G, Das T. Anti cancer effects of curcumin: cycle of life and death. Cell division. 2008;3(1):14.
4.Mackenzie GG, Queisser N, Wolfson ML, Fraga CG, Adamo AM, Oteiza PI. Curcumin induces cell‐arrest and apoptosis in association with the inhibition of constitutively active NF‐κB and STAT3 pathways in Hodgkin’s lymphoma cells. IJc. 2008; 123(1): 56-65.
5.Jung Y, Xu W, Kim H, Ha N, Neckers L. Curcumin-induced degradation of ErbB2: A role for the E3 ubiquitin ligase CHIP and the Michael reaction acceptor activity of curcumin. Biochim Biophys Acta Mol Cell Res. 2007; 1773(3): 383-390.
6.Banerjee M, Singh P, Panda D. Curcumin suppresses the dynamic instability of microtubules, activates the mitotic checkpoint and induces apoptosis in MCF‐7 cells. FEBS J. 2010; 277(16): 3437-3448.
7.Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini K. Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochim Biophys Acta Gen Subj. 2008; 1780(4): 673-679.
8.Shao ZM, Shen ZZ, Liu CH, Sartippour MR, Go VL, Heber D, et al. Curcumin exerts multiple suppressive effects on human breast carcinoma cells. IJC. 2002; 98(2): 234-240.
9.Shaikh J, Ankola D, Beniwal V, Singh D, Kumar MR. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci. 2009; 37(3-4): 223-230.
10.Song Z, Feng R, Sun M, Guo C, Gao Y, Li L. Curcumin-loaded PLGA-PEG-PLGA triblock copolymeric micelles: Preparation, pharmacokinetics and distribution in vivo. J Colloid Interface Sci. 2011; 354(1): 116-123.
11.Verderio P, Bonetti P, Colombo M, Pandolfi L, Prosperi D. Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells. Biomacromolecules. 2013; 14(3): 672-682.
12.Kurosaki T, Higuchi N, Kawakami S, Higuchi Y, Nakamura T, Kitahara T. Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer. Gene. 2012; 491(2): 205-209.
13.Patil P, Chaudhari P, Sahu M, Duragkar N. Review article on gene therapy. RJPPD. 2012; 4(2):77-83.
14.Sinha R, Kim GJ, Nie S, Shin DM. Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery. Mol. Cancer Ther. 2006; 5(8): 1909-1917.
15.Yazdian-Robati R, Ramezani M, Khedri M, Ansari N, Abnous K, Taghdisi SM. An aptamer for recognizing the transmembrane protein PDL-1 (programmed death-ligand 1), and its application to fluorometric single cell detection of human ovarian carcinoma cells. Microchim Acta. 2017; 184(10): 4029-4035.
16.Ansari N, Ghazvini K, Ramezani M, Shahdordizadeh M, Yazdian-Robati R, Abnous K. Selection of DNA aptamers against Mycobacterium tuberculosis Ag85A, and its application in a graphene oxide-based fluorometric assay Microchim Acta. 2018; 185(1): 21-29.
17.Bayat P, Taghdisi SM, Rafatpanah H, Abnous K, Ramezani M. In vitro selection of CD70 binding aptamer and its application in a biosensor design for sensitive detection of SKOV-3 ovarian cells. Talanta. 2019; 194: 399-405.
18.Huang YF, Shangguan D, Liu H, Phillips JA, Zhang X, Chen Y, et al. Molecular assembly of an aptamer–drug conjugate for targeted drug delivery to tumor cells. ChemBioChem. 2009; 10(5): 862-868.
19.Hashemi M, Shamshiri A, Saeedi M, Tayebi L, Yazdian-Robati R. Aptamer-conjugated PLGA nanoparticles for delivery and imaging of cancer therapeutic drugs. Arch Biochem Biophys. 2020: 108485.
20.Bates PJ, Reyes-Reyes EM, Malik MT, Murphy EM, O’toole MG, Trent JO. G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms. Biochim Biophys Acta Gen Subj. 2017; 1861(5): 1414-1428.
21.Yazdian-Robati R, Bayat P, Oroojalian F, Zargari M, Ramezani M, Taghdisi SM, et al. Therapeutic applications of AS1411 aptamer, an update review. Int J Biol Macromol. 2019; 155: 1420-1431
22.Shahgordi S, Sankian M, Yazdani Y, Mashayekhi K, Ayati SH, Sadeghi M, et al. Immune responses modulation by curcumin and allergen encapsulated into PLGA nanoparticles in mice model of rhinitis allergic through sublingual immunotherapy. Int Immunopharmacol. 2020; 84: 106525.
23.Ebrahimian M, Taghavi S, Mokhtarzadeh A, Ramezani M, Hashemi M. Co-delivery of doxorubicin encapsulated PLGA nanoparticles and Bcl-xL shRNA using alkyl-modified PEI into breast cancer cells. Appl Biochem Biotechnol. 2017; 183(1): 126-136.
24.D’Souza S. A review of in vitro drug release test methods for nano-sized dosage forms. IJAP. 2014; 2014.
25.Yu B, Pu Y, Liu J, Liao J, Chen K, Zhang J. Targeted delivery of emodin to adipocytes by aptamer-functionalized PEG-PLGA nanoparticles in vitro. J Drug Deliv Sci Technol. 2020: 101739.
26.Serova M, Bieche I, Sablin M, Pronk G, Vidaud M, Cvitkovic E, et al. Single agent and combination studies of pralatrexate and molecular correlates of sensitivity. Br J Cancer. 2011; 104(2): 272-280.
27.Chou T-C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006; 58(3): 621-681.
28.Rejhova A, Opattova A, Čumová A, Slíva D, Vodička P. Natural compounds and combination therapy in colorectal cancer treatment. Eur J Med Chem. 2018; 144: 582-594.
29.Jin H, Qiao F, Wang Y, Xu Y, Shang Y. Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol Rep. 2015; 34(5): 2782-2789.
30.Banerjee S, Singh SK, Chowdhury I, Lillard Jr JW, Singh R. Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer. Front. Biosci (Elite edition). 2017; 9: 235-245
31.Xu X, Qin J, Liu W. Curcumin inhibits the invasion of thyroid cancer cells via down-regulation of PI3K/Akt signaling pathway. Gene. 2014; 546(2): 226-232.
32.Shanmugam MK, Rane G, Kanchi MM, Arfuso F, Chinnathambi A, Zayed M. The multifaceted role of curcumin in cancer prevention and treatment. Molecules. 2015; 20(2): 2728-2769.
33.Epelbaum R, Schaffer M, Vizel B, Badmaev V, Bar-Sela G. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer. 2010; 62(8): 1137-1141.
34.Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin. Cancer Res. 2008; 14(14): 4491-4499.
35.Irving GR, Iwuji CO, Morgan B, Berry DP, Steward WP, Thomas A, et al. Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): study protocol for a randomised control trial. Trials. 2015; 16(1): 110-120
36.Abouzeid AH, Patel NR, Rachman IM, Senn S, Torchilin VP. Anti-cancer activity of anti-GLUT1 antibody-targeted polymeric micelles co-loaded with curcumin and doxorubicin. J Drug Target. 2013; 21(10): 994-1000.
37.Duan J, Mansour HM, Zhang Y, Deng X, Chen Y, Wang J, et al. Reversion of multidrug resistance by co-encapsulation of doxorubicin and curcumin in chitosan/poly(butyl cyanoacrylate) nanoparticles. Int J Pharm. 2012; 426(1-2): 193-201.
38.Guorgui J, Wang R, Mattheolabakis G, Mackenzie GG. Curcumin formulated in solid lipid nanoparticles has enhanced efficacy in Hodgkin’s lymphoma in mice. Arch Biochem Biophys. 2018; 648: 12-9.
39.Mujokoro B, Madani F, Esnaashari SS, Khosravani M, Adabi M. Combination and Co-delivery of Methotrexate and Curcumin: Preparation and In Vitro Cytotoxic Investigation on Glioma Cells. J Pharm Innov. 2019: 1-10.
40.Nguyen HT, Dai Phung C, Thapa RK, Pham TT, Tran TH, Jeong J-H, et al. Multifunctional nanoparticles as somatostatin receptor-targeting delivery system of polyaniline and methotrexate for combined chemo–photothermal therapy. Acta biomaterialia. 2018; 68: 154-167.
41.Hashemi M, Ebrahimian M. Recent advances in nanoformulations for co-delivery of curcumin and chemotherapeutic drugs. Nanomed J. 2017; 4(1): 1-7.
42.Saleh T, Soudi T, Shojaosadati SA. Aptamer functionalized curcumin-loaded human serum albumin (HSA) nanoparticles for targeted delivery to HER-2 positive breast cancer cells. Int J Biol Macromol. 2019;130: 109-116.
43.Ma Q, Qian W, Tao W, Zhou Y, Xue B. Delivery Of Curcumin Nanoliposomes Using Surface Modified With CD133 Aptamers For Prostate Cancer. Drug Des Devel Ther. 2019; 13: 4021-4033.
44.Mosafer J, Teymouri M, Abnous K, Tafaghodi M, Ramezani M. Study and evaluation of nucleolin-targeted delivery of magnetic PLGA-PEG nanospheres loaded with doxorubicin to C6 glioma cells compared with low nucleolin-expressing L929 cells. Mater Sci Eng C. 2017; 72: 123-133.
45.Hafezi Ghahestani Z, Alebooye Langroodi F, Mokhtarzadeh A, Ramezani M, Hashemi M. Evaluation of anti-cancer activity of PLGA nanoparticles containing crocetin. Artif Cells Nanomed Biotechnol. 2017; 45(5): 955-960.
46.Yoo HS, Park TG. Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA–PEG block copolymer. J Control Release. 2001; 70(1-2): 63-70.
47.Yazdian-Robati R, Ramezani M, Jalalian SH, Abnous K, Taghdisi SM. Targeted delivery of epirubicin to cancer cells by polyvalent aptamer system in vitro and in vivo. Pharm Res. 2016; 33(9): 2289-2297.
48.Taghdisi SM, Danesh NM, Ramezani M, Yazdian-Robati R, Abnous K. A novel AS1411 aptamer-based three-way junction pocket DNA nanostructure loaded with doxorubicin for targeting cancer cells in vitro and in vivo. Mol Pharm. 2018; 15(5): 1972-1978.
49.Abnous K, Danesh NM, Ramezani M, Lavaee P, Jalalian SH, Yazdian-Robati R, et al. A novel aptamer-based DNA diamond nanostructure for in vivo targeted delivery of epirubicin to cancer cells. RSC advances. 2017; 7(25): 15181-15188.
50.Kardani A, Yaghoobi H, Alibakhshi A, Khatami M. Inhibition of miR‐155 in MCF‐7 breast cancer cell line by gold nanoparticles functionalized with antagomir and AS1411 aptamer. J Cell Physiol. 2020; 23(10): 6887-6895.
51.Guo J, Gao X, Su L, Xia H, Gu G, Pang Z. Aptamer-functionalized PEG–PLGA nanoparticles for enhanced anti-glioma drug delivery. Biomaterials. 2011; 32(31): 8010-8020.
52.Aravind A, Jeyamohan P, Nair R, Veeranarayanan S, Nagaoka Y, Yoshida Y, et al. AS1411 aptamer tagged PLGA‐lecithin‐PEG nanoparticles for tumor cell targeting and drug delivery. Biotechnol Bioeng. 2012; 109(11): 2920-2931.
53.Yoo HS, Lee KH, Oh JE, Park TG. In vitro and in vivo anti-tumor activities of nanoparticles based on doxorubicin–PLGA conjugates. J Control Release. 2000; 68(3): 419-431.
54.Xu G, Yu X, Zhang J, Sheng Y, Liu G, Tao W. Robust aptamer–polydopamine-functionalized M-PLGA–TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy. Int J Nanomedicine. 2016; 11: 2953-2965.
55.Aravind A, Nair R, Raveendran S, Veeranarayanan S, Nagaoka Y, Fukuda T. Aptamer conjugated paclitaxel and magnetic fluid loaded fluorescently tagged PLGA nanoparticles for targeted cancer therapy. J Magn Magn Mater. 2013; 344: 116-123.
56.Saravanakumar K, Hu X, Shanmugam S, Chelliah R, Sekar P, Oh D-H. Enhanced cancer therapy with pH-dependent and aptamer functionalized doxorubicin loaded polymeric (poly D, L-lactic-co-glycolic acid) nanoparticles. Arch Biochem Biophys. 2019;671:143-151.
57.Cui Y, Zhang M, Zeng F, Jin H, Xu Q, Huang Y. Dual-targeting magnetic PLGA nanoparticles for codelivery of paclitaxel and curcumin for brain tumor therapy. ACS Appl Mater Interfaces. 2016; 8(47): 32159-32169.
58.Zhou L, Duan X, Zeng S, Men K, Zhang X, Yang L. Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis. Int J Nanomedicine. 2015; 10: 5205-5218.