AccScience Publishing / IJB / Volume 9 / Issue 6 / DOI: 10.36922/ijb.0048
Cite this article
163
Download
1610
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
RESEARCH ARTICLE

Printed cisplatin on microneedle arrays for transdermal delivery enhances olaparib-induced synthetic lethality in a mouse model of homologous recombination deficiency

Zoi Kanaki1 Alexandra Smina1 Chrysoula Chandrinou2 Fotini E. Koukouzeli1 Yiannis Ntounias1 Nikolaos Paschalidis1 Ilias Cheliotis2 Marina Makrygianni2 Jill Ziesmer3 Georgios A. Sotiriou3 Ioanna Zergioti2 Constantin Tamvakopoulos1 Apostolos Klinakis1*
Show Less
1 Biomedical Research Foundation Academy of Athens, 4 Soranou Efessiou Street, 11527 Athens, Greece
2 Department of Physics, School of Mathematical and Physical Sciences, National Technical University of Athens, Heroon Polytehneiou 9, 15780 Athens, Greece
3 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden
Submitted: 10 February 2023 | Accepted: 23 March 2023 | Published: 23 June 2023
(This article belongs to the Special Issue Laser bioprinting technologies)
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Small molecule inhibitors targeting specific proteins are claiming a continuously growing share in cancer therapy, more commonly in combination with traditional chemotherapeutic drugs. While these inhibitors are taken orally, the majority of chemotherapies are administered through intravenous injection in the hospital premises. Alternative routes for chemotherapy administration would allow more frequent administration at lower dosing by the patient oneself, allowing combination treatment with reduced side effects. Here, we employed laser printing to prepare microneedles for transdermal delivery of cisplatin. Combination treatment with cisplatin transdermally and the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib orally leads to effective treatment in a cancer xenograft mouse model in vivo, while reducing the risk for systemic side effects. This work opens new avenues in anti-cancer therapy by allowing the administration of chemotherapy without the need for intravenous injection alone or in combination with other therapies.

Keywords
Laser-induced forward transfer
Microneedles
Metronomic chemotherapy
Transdermal dosing
Synthetic lethality
Homologous recombination deficiency
Funding
This work has been co-financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call RESEARCH–CREATE–INNOVATE (project code: T1EDK-00976). G.A.S. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC Grant agreement no. 758705).
References
  1. Tsimberidou AM, Fountzilas E, Nikanjam M, et al., 2020, Review of precision cancer medicine: Evolution of the treatment paradigm. Cancer Treat Rev, 86(June): 102019. https://doi.org/10.1016/j.ctrv.2020.102019

 

  1. Zhong L, Li Y, Xiong L, et al., 2021, Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Signal Transduct Target Ther, 6(1): 201. https://doi.org/10.1038/s41392-021-00572-w

 

  1. Lord CJ, Ashworth A, 2017, PARP inhibitors: Synthetic lethality in the clinic. Science, 355(6330): 1152–1158. https://doi.org/10.1126/science.aam7344

 

  1. Ray Chaudhuri A, Nussenzweig A, 2017, The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol, 18(10): 610–621. https://doi.org/10.1038/nrm.2017.53

 

  1. Farmer H, McCabe N, Lord CJ, et al., 2005, Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 434(7035): 917–921. https://doi.org/10.1038/nature03445

 

  1. Bryant HE, Schultz N, Thomas HD, et al., 2005, Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature, 434(7035): 913–917. https://doi.org/10.1038/nature03443

 

  1. Menear KA, Adcock C, Boulter R, et al., 2008, 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4- fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem, 51(20): 6581–6591. https://doi.org/10.1021/jm8001263

 

  1. Moynahan ME, Jasin M, 2010, Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol, 11(3): 196–207. https://doi.org/10.1038/nrm2851

 

  1. Kim D, Nam HJ, 2022, PARP inhibitors: Clinical limitations and recent attempts to overcome them. Int J Mol Sci, 23(15). https://doi.org/10.3390/ijms23158412

 

  1. Vikas P, Borcherding N, Chennamadhavuni A, et al., 2020, Therapeutic potential of combining PARP inhibitor and immunotherapy in solid tumors. Front Oncol, 10(April): 570. https://doi.org/10.3389/fonc.2020.00570

 

  1. Klinakis A, Karagiannis D, Rampias T, 2020, Targeting DNA repair in cancer: Current state and novel approaches. Cell Mol Life Sci, 77(4): 677–703. https://doi.org/10.1007/s00018-019-03299-8

 

 

  1. Balmana J, Tung NM, Isakoff SJ, et al., 2014, Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors. Ann Oncol, 25(8): 1656–1663. https://doi.org/10.1093/annonc/mdu187

 

  1. Fong PC, Boss DS, Yap TA, et al., 2009, Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med, 361(2): 123–134. https://doi.org/10.1056/NEJMoa0900212

 

  1. Audeh MW, Carmichael J, Penson RT, et al., 2010, Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: A proof-of-concept trial. Lancet, 376(9737): 245–251. https://doi.org/10.1016/S0140-6736(10)60893-8

 

  1. Tutt A, Robson M, Garber JE, et al., 2010, Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: A proof-of-concept trial. Lancet, 376(9737): 235–244. https://doi.org/10.1016/S0140-6736(10)60892-6

 

  1. Gelmon KA, Tischkowitz M, Mackay H, et al., 2011, Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: A phase 2, multicentre, open-label, non-randomised study. Lancet Oncol, 12(9): 852–861. https://doi.org/10.1016/S1470-2045(11)70214-5

 

  1. Larraneta E, Lutton REM, Woolfson AD, et al., 2016, Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Mat Sci Eng R, 104(June): 1–32. https://doi.org/10.1016/j.mser.2016.03.001

 

  1. Pearton M, Saller V, Coulman SA, et al., 2012, Microneedle delivery of plasmid DNA to living human skin: Formulation coating, skin insertion and gene expression. J Control Release, 160(3): 561–569. https://doi.org/10.1016/j.jconrel.2012.04.005

 

  1. Zhao X, Coulman SA, Hanna SJ, et al., 2017, Formulation of hydrophobic peptides for skin delivery via coated microneedles. J Control Release, 265(November): 2–13. https://doi.org/10.1016/j.jconrel.2017.03.015

 

 

  1. Lan X, Zhu W, Huang X, et al., 2020, Microneedles loaded with anti-PD-1-cisplatin nanoparticles for synergistic cancer immuno-chemotherapy. Nanoscale, 12(36): 18885–18898. https://doi.org/10.1039/d0nr04213g
  2. Lan X, She J, Lin DA, et al., 2018, Microneedle-mediated delivery of lipid-coated cisplatin nanoparticles for efficient and safe cancer therapy. ACS Appl Mater Interfaces, 10(39): 33060–33069. https://doi.org/10.1021/acsami.8b12926

 

  1. Fu JJ, Li CW, Liu Y, et al., 2020, The microneedles carrying cisplatin and IR820 to perform synergistic chemo-photodynamic therapy against breast cancer. J Nanobiotechnol, 18(1): 146. https://doi.org/10.1186/s12951-020-00697-0

 

  1. Uddin MJ, Scoutaris N, Klepetsanis P, et al., 2015, Inkjet printing of transdermal microneedles for the delivery of anticancer agents. Int J Pharm, 494(2): 593–602. https://doi.org/10.1016/j.ijpharm.2015.01.038

 

  1. Ross S, Scoutaris N, Lamprou D, et al., 2015, Inkjet printing of insulin microneedles for transdermal delivery. Drug Deliv Transl Res, 5(4): 451–461. https://doi.org/10.1007/s13346-015-0251-1

 

  1. Uddin MJ, Scoutaris N, Economidou SN, et al., 2020, 3D printed microneedles for anticancer therapy of skin tumours. Mater Sci Eng C Mater Biol Appl, 107(February): 110248. https://doi.org/10.1016/j.msec.2019.110248

 

  1. Tarbox TN, Watts AB, Cui Z, et al., 2018, An update on coating/manufacturing techniques of microneedles. Drug Deliv Transl Res, 8(6): 1828–1843. https://doi.org/10.1007/s13346-017-0466-4

 

  1. Haj-Ahmad R, Khan H, Arshad MS, et al., 2015, Microneedle coating techniques for transdermal drug delivery. Pharmaceutics, 7(4): 486–502. https://doi.org/10.3390/pharmaceutics7040486

 

  1. Papazoglou S, Zergioti I, 2017, Laser induced forward transfer (LIFT) of nano-micro patterns for sensor applications. Microelectron Eng, 182(October): 25–34. https://doi.org/10.1016/j.mee.2017.08.003

 

  1. Kanaki Z, Chandrinou C, Orfanou IM, et al., 2022, Laser-induced forward transfer printing on microneedles for transdermal delivery of gemcitabine. Int J Bioprint, 8(2): 554. https://doi.org/10.18063/ijb.v8i2.554

 

  1. Hall MD, Telma KA, Chang KE, et al., 2014, Say no to DMSO: dimethylsulfoxide inactivates cisplatin, carboplatin, and other platinum complexes. Cancer Res, 74(14): 3913–3922. https://doi.org/10.1158/0008-5472.CAN-14-0247

 

  1. Ziesmer J, Tajpara P, Hempel NJ, et al., 2021, Vancomycin-loaded microneedle arrays against methicillin-resistant Staphylococcus aureus skin infections. Adv Mater Technol, 6(7): 2001307. https://doi.org/10.1002/admt.202001307

 

 

  1. Shaik AN, Altomare DA, Lesko LJ, et al., 2017, Development and validation of a LC-MS/MS assay for quantification of cisplatin in rat plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci, 1046(March): 243–249. https://doi.org/10.1016/j.jchromb.2016.11.027

 

  1. Coughlan AM, Harmon C, Whelan S, et al., 2016, Myeloid engraftment in humanized mice: Impact of granulocyte-colony stimulating factor treatment and transgenic mouse strain. Stem Cells Dev, 25(7): 530–541. https://doi.org/10.1089/scd.2015.0289

 

  1. Shultz LD, Lyons BL, Burzenski LM, et al., 2005, Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol, 174(10): 6477–6489. https://doi.org/10.4049/jimmunol.174.10.6477

 

  1. Kanaki Z, Voutsina A, Markou A, et al., 2021, Generation of non-small cell lung cancer patient-derived xenografts to study intratumor heterogeneity. Cancers (Basel), 13(10). https://doi.org/10.3390/cancers13102446

 

  1. Falcon-Suarez IH, Livo K, Callow B, et al., 2020, Geophysical early warning of salt precipitation during geological carbon sequestration. Sci Rep, 10(1): 16472. https://doi.org/10.1038/s41598-020-73091-3

 

  1. Johnsson A, Olsson C, Nygren O, et al., 1995, Pharmacokinetics and tissue distribution of cisplatin in nude mice: Platinum levels and cisplatin-DNA adducts. Cancer Chemother Pharmacol, 37(1–2): 23–31. https://doi.org/10.1007/BF00685625

 

  1. Rampias T, Karagiannis D, Avgeris M, et al., 2019, The lysine-specific methyltransferase KMT2C/MLL3 regulates DNA repair components in cancer. EMBO Rep, 20(3). https://doi.org/10.15252/embr.201846821

 

  1. Ray Chaudhuri A, Callen E, Ding X, et al., 2016, Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature, 535(7612): 382–387. https://doi.org/10.1038/nature18325

 

  1. Chang A, Liu L, Ashby JM, et al., 2021, Recruitment of KMT2C/MLL3 to DNA damage sites mediates DNA damage responses and regulates PARP inhibitor sensitivity in cancer. Cancer Res, 81(12): 3358–3373. https://doi.org/10.1158/0008-5472.CAN-21-0688

 

  1. Diossy M, Sztupinszki Z, Borcsok J, et al., 2021, A subset of lung cancer cases shows robust signs of homologous recombination deficiency associated genomic mutational signatures. NPJ Precis Oncol, 5(1): 55. https://doi.org/10.1038/s41698-021-00199-8

 

 

 

  1. Zhou Z, Ding Z, Yuan J, et al., 2022, Homologous recombination deficiency (HRD) can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients. J Hematol Oncol, 15(1): 62. https://doi.org/10.1186/s13045-022-01283-7

 

  1. Wu S, Zhang Y, Zhang Y, et al., 2022, Mutational landscape of homologous recombination-related genes in small-cell lung cancer. Cancer Med, 12(4): 4486–4495. https://doi.org/10.1002/cam4.5148

 

  1. Chang Q, Ornatsky OI, Koch CJ, et al., 2015, Single-cell measurement of the uptake, intratumoral distribution and cell cycle effects of cisplatin using mass cytometry. Int J Cancer, 136(5): 1202–1209. https://doi.org/10.1002/ijc.29074

 

  1. Skavatsou E, Semitekolou M, Morianos I, et al., 2021, Immunotherapy combined with metronomic dosing: An effective approach for the treatment of NSCLC. Cancers (Basel), 13(8). https://doi.org/10.3390/cancers13081901

 

  1. Ameri M, Kadkhodayan M, Nguyen J, et al., 2014, Human growth hormone delivery with a microneedle transdermal system: Preclinical formulation, stability, delivery and PK of therapeutically relevant doses. Pharmaceutics, 6(2): 220–234. https://doi.org/10.3390/pharmaceutics6020220

 

  1. Chen X, Prow TW, Crichton ML, et al., 2009, Dry-coated microprojection array patches for targeted delivery of immunotherapeutics to the skin. J Control Release, 139(3): 212–220. https://doi.org/10.1016/j.jconrel.2009.06.029

 

  1. Vrdoljak A, McGrath MG, Carey JB, et al., 2012, Coated microneedle arrays for transcutaneous delivery of live virus vaccines. J Control Release, 159(1): 34–42. https://doi.org/10.1016/j.jconrel.2011.12.026

 

  1. Gill HS, Prausnitz MR, 2007, Coating formulations for microneedles. Pharm Res, 24(7): 1369–1380. https://doi.org/10.1007/s11095-007-9286-4

 

  1. Ingrole RSJ, Gill HS, 2019, Microneedle coating methods: A review with a perspective. J Pharmacol Exp Ther, 370(3): 555–569. https://doi.org/10.1124/jpet.119.258707

 

  1. Bhatnagar S, Kumari P, Pattarabhiran SP, et al., 2018, Zein microneedles for localized delivery of chemotherapeutic agents to treat breast cancer: Drug loading, release behavior, and skin permeation studies. AAPS PharmSciTech, 19(4): 1818–1826. https://doi.org/10.1208/s12249-018-1004-5

 

  1. Infante JR, Benhadji KA, Dy GK, et al., 2015, Phase 1b study of the oral gemcitabine ‘Pro-drug’ LY2334737 in combination with capecitabine in patients with advanced solid tumors. Invest New Drugs, 33(2): 432–439. https://doi.org/10.1007/s10637-015-0207-9

 

  1. Rose M, Burgess JT, O’Byrne K, et al., 2020, PARP inhibitors: Clinical relevance, mechanisms of action and tumor resistance. Front Cell Dev Biol, 8(September): 564601. https://doi.org/10.3389/fcell.2020.564601

 

  1. Brown TJ, Reiss KA, 2021, PARP inhibitors in pancreatic cancer. Cancer J, 27(6): 465–475. https://doi.org/10.1097/PPO.0000000000000554

 

  1. Beatson EL, Chau CH, Price DK, et al., 2022, PARP inhibitors on the move in prostate cancer: Spotlight on Niraparib & update on PARP inhibitor combination trials. Am J Clin Exp Urol, 10(4): 252–257.

 

  1. van der Wiel AMA, Schuitmaker L, Cong Y, et al., 2022, Homologous recombination deficiency scar: Mutations and beyond-implications for precision oncology. Cancers (Basel), 14(17). https://doi.org/10.3390/cancers14174157

 

  1. Frankenberg-Schwager M, Kirchermeier D, Greif G, et al., 2005, Cisplatin-mediated DNA double-strand breaks in replicating but not in quiescent cells of the yeast Saccharomyces cerevisiae. Toxicology, 212(2–3): 175–184. https://doi.org/10.1016/j.tox.2005.04.015

 

  1. Schierl R, Rohrer B, Hohnloser J, 1995, Long-term platinum excretion in patients treated with cisplatin. Cancer Chemother Pharmacol, 36(1): 75–78. https://doi.org/10.1007/BF00685736
Conflict of interest
The authors declare no conflict of interest.
Share
Back to top
International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing