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Journal of Nanoparticle Research

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01-06-2023 | Research paper

Phytoglycogen-dsRNA nanoparticles demonstrate differential cytotoxicity and immunostimulatory potential in two ovarian cancer cell lines

Authors: A. Lewis, A. Tran, N. L. Aldor, N. A. Jadaa, T. Feng, E. Moore, S. J. DeWitte-Orr, S. J. Poynter

Published in: Journal of Nanoparticle Research | Issue 6/2023

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Abstract

Ovarian cancer is a leading cause of cancer mortality in women, and novel treatments with improved efficacy are needed to fight ovarian cancer. Double-stranded (ds) RNA, including the synthetic polyinosinic cytidylic acid (poly (I:C), has shown promise as a cancer therapeutic. Phytoglycogen derived from sweet corn, nanodendrix (NDX) is a carrier for dsRNA. The responsiveness to NDX-delivered poly (I:C), NDX-poly (I:C), was tested in two ovarian cancer cell lines, SKOV-3 and OVCAR-3, previously identified as dsRNA-resistant and dsRNA-sensitive, respectively. NDX bound poly (I:C) at a w/w ratio of 2:1 NDX:poly (I:C) and poly (I:C)-NDX was tested for biological activity through uptake and two therapeutic modes of action, cytotoxicity, and immune stimulation. Immunocytochemistry demonstrated both cells bound to poly (I:C)-NDX. In OVCAR-3, poly (I:C)-NDX caused significant cell death, even at concentrations as low as 62.5 ng/mL; no cell death was observed with poly (I:C) alone at concentrations up to 5 μg/mL in SKOV-3 and 0.5 μg/mL in OVCAR-3. In both cell lines poly (I:C)-NDX stimulated the production of CXCL10 protein and transcripts, an innate immune chemokine, and at significantly higher levels than poly (I:C) alone. Interestingly, in response to poly (I:C)-NDX SKOV-3 produced a more robust immune response and higher levels of capase-3/-7 activation compared to OVCAR-3, despite showing no significant cell death. Poly (I:C)-NDX represents a robust and multifunctional therapy, potentiating poly (I:C) and sensitizing resistant cells. Additionally, the SKOV-3 and OVCAR-3 combination represents a powerful comparative model to help unravel dsRNA-mediated immune responses in ovarian cancer cells.

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Coburn SB, Bray F, Sherman ME, Trabert B (2017) International patterns and trends in ovarian cancer incidence, overall and by histologic subtype. Int J Cancer 140(11):2451–2460. https://doi.org/10.1002/ijc.30676CrossRef

Chandra A, Pius C, Nabeel M, Nair M, Vishwanatha JK, Ahmad S, Basha R (2019) Ovarian cancer: current status and strategies for improving therapeutic outcomes. Cancer Med 8(16):7018–7031. https://doi.org/10.1002/cam4.2560CrossRef

Bast RC, Hennessy B, Mills GB (2009) The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer 9(6):415–428. https://doi.org/10.1038/nrc2644CrossRef

Lengyel E (2010) Ovarian cancer development and metastasis. Am J Pathol 177(3):1053–1064. https://doi.org/10.2353/ajpath.2010.100105CrossRef

Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T (2006) TLR3 can directly trigger apoptosis in human cancer cells. J Immunol 176(8):4894–4901. https://doi.org/10.4049/jimmunol.176.8.4894CrossRef

Van DN, Roberts CF, Marion JD, Lépine S, Harikumar KB, Schreiter J, Dumur CI, Fang Z, Spiegel S, Bell JK (2012) Innate immune agonist, dsRNA, induces apoptosis in ovarian cancer cells and enhances the potency of cytotoxic chemotherapeutics. FASEB J 26(8):3188–3198. https://doi.org/10.1096/fj.11-202333CrossRef

Bianchi F, Pretto S, Tagliabue E, Balsari A, Sfondrini L (2017) Exploiting poly (I: C) to induce cancer cell apoptosis. Cancer Biol Ther 18(10):747–756. https://doi.org/10.1080/15384047.2017.1373220CrossRef

Ammi R, De Waele J, Willemen Y, Van Brussel I, Schrijvers DM, Lion E, Smits EL (2015) Poly (I: C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs. Pharmacol Ther 146:120–131. https://doi.org/10.1016/j.pharmthera.2014.09.010CrossRef

Palchetti S, Starace D, De Cesaris P, Filippini A, Ziparo E, Riccioli A (2015) Transfected poly (I: C) activates different dsRNA receptors, leading to apoptosis or immunoadjuvant response in androgen-independent prostate cancer cells. J Biol Chem 290(9):5470–5483. https://doi.org/10.1074/jbc.M114.601625CrossRef

10.

Nguyen TA, Smith BR, Tate MD, Belz GT, Barrios MH, Elgass KD, Weisman AS, Baker PJ, Preston SP, Whitehead L, Garnham A (2017) SIDT2 transports extracellular dsRNA into the cytoplasm for innate immune recognition. Immunity. 47(3):498–509. https://doi.org/10.1016/j.immuni.2017.08.007CrossRef

11.

DeWitte-Orr SJ, Collins SE, Bauer CM, Bowdish DM, Mossman KL (2010) An accessory to the ‘Trinity’: SR-As are essential pathogen sensors of extracellular dsRNA, mediating entry and leading to subsequent type I IFN responses. PLoS Pathog 6(3):e1000829. https://doi.org/10.1371/journal.ppat.1000829CrossRef

12.

Hasselmann DO, Rappl G, Tilgen W, Reinhold U (2001) Extracellular tyrosinase mRNA within apoptotic bodies is protected from degradation in human serum. Clin Chem 47(8):1488–1489. https://doi.org/10.1093/clinchem/47.8.1488CrossRef

13.

Ultimo A, Giménez C, Bartovsky P, Aznar E, Sancenón F, Marcos MD, Amoros P, Bernardo AR, Martinez-Manez R, Jimenez-Lara AM, Murguia JR (2016) Targeting innate immunity with dsRNA-conjugated mesoporous silica nanoparticles promotes antitumor effects on breast cancer cells. Chemistry 22(5):1582–1586. https://doi.org/10.1002/chem.201504629CrossRef

14.

Elhaj Baddar Z, Gurusamy D, Laisney J, Tripathi P, Palli SR, Unrine JM (2020) Polymer-coated hydroxyapatite nanocarrier for double-stranded RNA delivery. J Agric Food Chem 68(25):6811–6818. https://doi.org/10.1021/acs.jafc.0c02182CrossRef

15.

Qu J, Hou Z, Han Q, Zhang C, Tian Z, Zhang J (2013) Poly (I:C) exhibits an anti-cancer effect in human gastric adenocarcinoma cells which is dependent on RLRs. Int Immunopharmacol 17(3):814–820. https://doi.org/10.1016/j.intimp.2013.08.013CrossRef

16.

Massich MD, Giljohann DA, Schmucker AL, Patel PC, Mirkin CA (2010) Cellular response of polyvalent oligonucleotide− gold nanoparticle conjugates. ACS Nano 4(10):5641–5646. https://doi.org/10.1021/nn102228sCrossRef

17.

Komal A, Noreen M, El-Kott AF (2021) TLR3 agonists: RGC100, ARNAX, and poly-IC: A comparative review. Immunol Res 69(4):312–322. https://doi.org/10.1007/s12026-021-09203-6CrossRef

18.

Le Naour J, Galluzzi L, Zitvogel L, Kroemer G, Vacchelli E (2020) Trial watch: TLR3 agonists in cancer therapy. Oncoimmunol 9(1):1771143. https://doi.org/10.1080/2162402X.2020.1771143CrossRef

19.

Deci MB, Liu M, Dinh QT, Nguyen J (2018) Precision engineering of targeted nanocarriers. Wiley Interdiscip Rev Nanomed Nanobiotechnol 10(5):e1511. https://doi.org/10.1002/wnan.1511CrossRef

20.

Nickels JD, Atkinson J, Papp-Szabo E, Stanley C, Diallo SO, Perticaroli S, Baylis B, Mahon P, Ehlers G, Katsaras J, Dutcher JR (2016) Structure and hydration of highly-branched, monodisperse phytoglycogen nanoparticles. Biomacromolecules 17(3):735–743. https://doi.org/10.1021/acs.biomac.5b01393CrossRef

21.

Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4(1):26–49. https://doi.org/10.1002/smll.200700595CrossRef

22.

Alkie TN, de Jong J, Jenik K, Klinger KM, DeWitte-Orr SJ (2019) Enhancing innate antiviral immune responses in rainbow trout by double-stranded RNA delivered with cationic phytoglycogen nanoparticles. Sci Rep 9(1). https://doi.org/10.1038/s41598-019-49931-2

23.

Semple SL, Alkie TN, Jenik K, Warner BM, Tailor N, Kobasa D, DeWitte-Orr SJ (2022) More tools for our toolkit: the application of HEL-299 cells and dsRNA-nanoparticles to study human coronaviruses in vitro. Virus Res 321:198925. https://doi.org/10.1016/j.virusres.2022.198925CrossRef

24.

NCBI. Poly I:C. National Library of Medicine. n.d. (accessed 2022-07-19)

25.

Besford QA, Cavalieri F, Caruso F (2019) Glycogen as a building block for advanced biological materials. Adv Mater 32(18). https://doi.org/10.1016/j.carbpol.2021.119041

26.

Lu C, Li Z, Chang L, Dong Z, Guo P, Shen G, Xia Q, Zhao P (2019) Efficient delivery of dsRNA and DNA in cultured silkworm cells for gene function analysis using PAMAM dendrimers system. Insects 11(1):12. https://doi.org/10.3390/insects11010012CrossRef

27.

Khodadust R, Mutlu P, Yalcın S, Unsoy G, Gunduz U (2013) Polyinosinic: polycytidylic acid loading onto different generations of PAMAM dendrimer-coated magnetic nanoparticles. J Nanopart Res 15(8):1–12. https://doi.org/10.1007/s11051-013-1860-6CrossRef

28.

Zhao J, Zhang Z, Xue Y, Wang G, Cheng Y, Pan Y, Zhao S, Hou Y (2018) Anti-tumor macrophages activated by ferumoxytol combined or surface-functionalized with the TLR3 agonist poly (I: C) promote melanoma regression. Theranostics 8(22):6307. https://doi.org/10.7150/thno.29746CrossRef

29.

Nguyen TA, Whitehead L, Pang KC (2018) Quantification of extracellular double-stranded RNA uptake and subcellular localization using flow cytometry and confocal microscopy. Bio Protoc 8(12). https://doi.org/10.21769/BioProtoc.2890

30.

Karin N, Razon H (2018) Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity. Cytokine 109:24–28. https://doi.org/10.1016/j.cyto.2018.02.012CrossRef

31.

Wendel M, Galani IE, Suri-Payer E, Cerwenka A (2008) Natural killer cell accumulation in tumors is dependent on IFN-gamma and CXCR3 ligands. Cancer Res 68(20):8437–8445. https://doi.org/10.1158/0008-5472.CAN-08-1440CrossRef

32.

Liu M, Guo S, Stiles JK (2011) The emerging role of CXCL10 in cancer. Oncol Lett 2(4):583–589. https://doi.org/10.3892/ol.2011.300CrossRef

33.

Sui Y, Potula R, Dhillon N, Pinson D, Li S, Nath A, Anderson C, Turchan J, Kolson D, Narayan O, Buch S (2004) Neuronal apoptosis is mediated by CXCL10 overexpression in simian human immunodeficiency virus encephalitis. Am J Pathol 164(5):1557–1566. https://doi.org/10.1016/S0002-9440(10)63714-5CrossRef

34.

Kübler K, Tho Pesch C, Gehrke N, Riemann S, Daßler J, Coch C, Landsberg J, Wimmenauer V, Pölcher M, Rudlowski C, Tüting T (2011) Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly (I: C) leads to myeloid cell maturation and activates NK cells. E J Immuno l41(10):3028–3039. https://doi.org/10.1002/eji.201141555CrossRef

35.

Riss TL, O’Brien MA, Moravec RA, Kupcho K, Niles AL (2021) Apoptosis marker assays for HTS. In: Assay guidance manual. National Center for Biotechnology Information

36.

Kavanagh E, Rodhe J, Burguillos MA, Venero JL, Joseph B (2014) Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia. Cell Death Dis 5(12):e1565-e. https://doi.org/10.1038/cddis.2014.514CrossRef

37.

Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 17:2215–2223. https://doi.org/10.1093/emboj/17.8.2215CrossRef

38.

Huang HK, Joazeiro CA, Bonfoco E, Kamada S, Leverson JD, Hunter T (2000) The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7. J Biol Chem 275(35):26661–26664. https://doi.org/10.1074/jbc.C000199200CrossRef

39.

Sun X, Liu H (2020) Nucleic acid nanostructure assisted immune modulation. ACS Appl Bio Mater 3(5):2765–2778. https://doi.org/10.1021/acsabm.9b01195CrossRef

40.

Boyd MR, Paull KD (1995) Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev Res 34:91–109. https://doi.org/10.1002/ddr.430340203CrossRef

41.

Poynter SJ, DeWitte-Orr SJ (2017) Visualizing virus-derived dsRNA using antibody-independent and-dependent methods. In: Innate Antiviral Immunity 103-118. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7237-1_5CrossRef

Title: Phytoglycogen-dsRNA nanoparticles demonstrate differential cytotoxicity and immunostimulatory potential in two ovarian cancer cell lines
Authors: A. Lewis
A. Tran
N. L. Aldor
N. A. Jadaa
T. Feng
E. Moore
S. J. DeWitte-Orr
S. J. Poynter
Publication date: 01-06-2023
Publisher: Springer Netherlands
Published in: Journal of Nanoparticle Research / Issue 6/2023
Print ISSN: 1388-0764
Electronic ISSN: 1572-896X
DOI: https://doi.org/10.1007/s11051-023-05758-7

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