Topical control of wound healing by nanocerium in carcinogenesis

Ekaterina V. Blinova; Denis N. Shimanovsky; Ivar S. Struts; Kirill D. Blinov; Varvara S. Berseneva; Evgenii V. Grebenkin; Igor V. Lunev; Anna V. Epishkina; Ekaterina A. Koreeva; Masud A. R. Farakhmand; Sergey P. Timoshkin; Dmirty S. Blinov; Evgenia V.  Shikh

doi:10.18413/rrpharmacology.12.1068

Авторы

Ekaterina V. Blinova Sechenov University https://orcid.org/0000-0003-0050-0251
Denis N. Shimanovsky Sechenov University https://orcid.org/0000-0002-8211-8138
Ivar S. Struts Sechenov University https://orcid.org/0009-0001-9443-1244
Kirill D. Blinov Sechenov University https://orcid.org/0009-0002-7195-2191
Varvara S. Berseneva Sechenov University https://orcid.org/0009-0007-8972-541X
Evgenii V. Grebenkin National Research Nuclear University MEPhI; Moscow Botkin Multidisciplinary Scientific-Clinical Center https://orcid.org/0000-0002-4990-6722
Igor V. Lunev National Research Nuclear University MEPhI https://orcid.org/0009-0003-9514-0814
Anna V. Epishkina National Research Nuclear University MEPhI https://orcid.org/0000-0002-7824-7949
Ekaterina A. Koreeva National Research Nuclear University MEPhI https://orcid.org/0009-0009-4214-9974
Masud A. R. Farakhmand National Research Nuclear University MEPhI https://orcid.org/0009-0009-6828-9078
Sergey P. Timoshkin National Research Nuclear University MEPhI https://orcid.org/0000-0001-5518-6859
Dmirty S. Blinov Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology https://orcid.org/0000-0002-8385-4356
Evgenia V. Shikh Sechenov University https://orcid.org/0000-0001-6589-7654

DOI:

https://doi.org/10.18413/rrpharmacology.12.1068

Аннотация

Introduction: Skin wound healing in cancer patients is a complex issue, influenced by both the tumor process itself and the effects of antitumor therapy. This study assessed the efficacy of various skin wound treatment regimens in mice with transplanted Lewis lung carcinoma (LLC).

Materials and Methods: 72 C57BL/6 mice were divided into six groups, including control, topical application of 1% cerium nanoparticles colloidal solution, 5% dexpanthenol spray, 100 mg/kg cyclophosphamide solution, and a combination of these.

Results and Discussion: It was found that topical application of cerium nanoparticles without chemotherapeutic treatment significantly shortened the time of wound regeneration to 16.5±1.0 days (p≤0.05) and reduces a postoperative scar (6±0.3 mm², p≤ 0.0001). Systemic chemotherapy treatment increased the healing time (22.5±1.0 days) and scar area (55.0±0.7 mm²), while reducing a tumor volume by 34% comparing to such in the control group. Combination therapy by dexpanthenol and cyclophosphamide promoted an antitumor effect and accelerated a tissue repair (16.3 ± 0.8 days). At the same time, local application of cerium nanoparticles did not alter regeneration (21.5 ± 1.0 days); however, the scar area was smaller (10.0 ± 0.7 mm²). Histological analysis revealed that the highest vascular density and maturity of granulation tissue in a wound were observed when treated cerium nanoparticles, while epithelial cell proliferation was reduced by cyclophosphamide.

Conclusion: The obtained data indicate the potential of topical application daily for 7 days of 1% nanocerium to accelerate wound regeneration in cancer patients without chemotherapy, and 5% dexpanthenol to accelerate skin regeneration in cancer patients receiving chemotherapy.

Графическая аннотация

Ключевые слова:

Lewis lung carcinoma, mice, nanocerium, dexpanthenol, cyclophosphamide, regeneration, wound healing gel

Библиографические ссылки

Behranvand N, Nasri F, Zolfaghari Emameh R, Khani P, Hosseini A, Garssen J, Falak R. (2022) Chemotherapy: a double-edged sword in cancer treatment. Cancer Immunology, Immunotherapy 71(3): 507–526. https://doi.org/10.1007/s00262-021-03034-y [PubMed] [PMC]

Bosari S, Lee AKC, DeLellis RA, Wiley BD, Heatley GJ, Silverman ML (1992) Microvessel quantitation and prognosis in invasive breast carcinoma. Human Pathology 23(7): 755–761. https://doi.org/10.1016/0046-8177(92)90344-3 [PubMed]

Carvalho PM, Felício MR, Santos NC, Gonçalves S, Domingues MM (2018) Application of light scattering techniques to nanoparticle characterization and development. Frontiers in Chemistry 6: 237. https://doi.org/10.3389/fchem.2018.00237 [PubMed] [PMC]

Deptuła M, Zieliński J, Wardowska A, Pikuła M (2010) Wound healing complications in oncological patients: perspectives for cellular therapy. Postȩpy Dermatologii i alergologii 36(2): 139–146. https://doi.org/10.5114/ada.2018.72585 [PubMed] [PMC]

Fadilah NIM, Phang SJ, Kamaruzaman N, Salleh A, Zawani M, Sanyal A, Maarof M, Fauzi MB (2023) Antioxidant biomaterials in cutaneous wound healing and tissue regeneration: a critical review. Antioxidants 12(4): 787. https://doi.org/10.3390/antiox12040787 [PubMed] [PMC]

Kuo PJ, Lin PC, Hsieh CH (2025) Wound healing in cancer patients under immunotherapy. International Journal of Surgery 111(10): 7087–7098. https://doi.org/10.1097/JS9.0000000000002819 [PubMed] [PMC]

Levra Levron C, Elettrico L, Duval C, Piacenti G, Proserpio V, Donati G (2025) Bridging tissue repair and epithelial carcinogenesis: epigenetic memory and field cancerization. Cell Death and Differentiation 32(1): 78–89. https://doi.org/10.1038/s41418-023-01254-6 [PubMed] [PMC]

Matsuyama K, Chiba Y, Sasaki M, Tanaka H, Muraoka R, Tanigawa N (1998) Tumor angiogenesis as a prognostic marker in operable non-small cell lung cancer. Annals of Thoracic Surgery 65(5): 1405–1409. https://doi.org/10.1016/s0003-4975(97)01416-1[PubMed]

Miller ID, Payne S, Ogston KN (2002) A new histological grading system to assess response of breast cancer to primary chemotherapy. International Journal of Oncology 20(4): 791–796.

Nelson BC, Johnson ME, Walker ML, Riley KR, Sims CM (2016) Antioxidant cerium oxide nanoparticles in biology and medicine. Antioxidants 5(2): 15. https://doi.org/10.3390/antiox5020015 [PubMed] [PMC]

Nwosu N (2024) Cancer: A disease of modern times? Cureus 16(11): e74666.https://doi.org/10.7759/cureus.74666 [PubMed] [PMC]

Payne WG, Naidu DK, Wheeler CK, Barkoe D, Mentis M, Salas RE, Smith DJ Jr, Robson MC (2008) Wound healing in patients with cancer. Eplasty 8: e9. [PubMed] [PMC]

Shekhter AB, Pekshev AV, Vagapov AB, Butenko AV, Fayzullin AL, Rudenko TG, Sharapov NA, Serejnikova NB, Vasilets VN (2020) Dose-dependent effect of plasma-chemical NO-containing gas flow on wound healing. An experimental study. Clinical Plasma Medicine 19-20: 100101. https://doi.org/10.1016/j.cpme.2020.100101

Słonimska P, Sachadyn P, Zieliński J, Skrzypski M, Pikuła M (2024) Chemotherapy-mediated complications of wound healing: An understudied side effect. Advances in Wound Care 13(4): 187–199. https://doi.org/10.1089/wound.2023.0097 [PubMed] [PMC]

Sundaram GM, Quah S, Sampath P (2018) Cancer: The dark side of wound healing. The FEBS Journal 285(24): 4516–4534. https://doi.org/10.1111/febs.14586 [PubMed]

Zawrzykraj M, Deptuła M, Kondej K, Tymińska A, Pikuła M (2023) The effect of chemotherapy and radiotherapy on stem cells and wound healing. Current perspectives and challenges for cell-based therapies. Biomédecine and Pharmacothérapie 168: 115781. https://doi.org/10.1016/j.biopha.2023.115781 [PubMed]

Вклад авторов

Ekaterina V. Blinova, Sechenov University

Doctor Habil. of Medical Sciences, Professor of the Clinical Pharmacology and Internal Disease Department, Sechenov University; Head of Fundamental Medicine Department, MEPhI, Moscow, Russia; e-mail: bev-sechenov@mail.ru; ORCID ID: https://orcid.org/0000-0003-0050-0251. The author organized the project, analyzed the collected data, wrote and revised the manuscript.

Denis N. Shimanovsky, Sechenov University

Postgraduate student, Department of the Operative Surgery, Sechenov University, Moscow, Russia; e-mail: mailalamow@gmail.com; ORCID ID: https://orcid.org/0000-0002-8211-8138. The author conducted the experiments on LLC and prepared the manuscript for submission.

Ivar S. Struts, Sechenov University

Student, Institute of Clinical Medicine, Sechenov University, Moscow, Russia; e-mail: ivarstrutz@mail.ru; ORCID ID: https://orcid.org/0009-0001-9443-1244. The author conducted the experiments on LLC and prepared the manuscript for submission.

Kirill D. Blinov, Sechenov University

Student, Institute of Clinical Medicine, Sechenov University, Moscow, Russia; e-mail: pyrk2@yandex.ru; ORCID ID: https://orcid.org/0009-0002-7195-2191. The author conducted the experiments and statistically processed the obtained data.

Varvara S. Berseneva, Sechenov University

Student, Institute of Clinical Medicine, Sechenov University, Moscow, Russia; e-mail: va264@gmail.com; ORCID ID: https://orcid.org/0009-0007-8972-541X. The author conducted the experiments and statistically processed the obtained data.

Evgenii V. Grebenkin, National Research Nuclear University MEPhI; Moscow Botkin Multidisciplinary Scientific-Clinical Center

Candidate of Medical Sciences, Associate Professor of Fundamental Medicine Department, MEPhI; pathologist of Moscow Botkin Multidisciplinary Scientific-Clinical Center, Moscow, Russia; e-mail: grebenkin_urolog@mail.ru; ORCID ID: https://orcid.org/0000-0002-4990-6722. The author conducted the experiments on LLC and prepared the manuscript for submission.

Igor V. Lunev, National Research Nuclear University MEPhI

Postgraduate student, Department of Nuclear Medicine, Moscow Engineering Physics Institute,MEPhI, Moscow, Russia; e-mail: igorpsdgig@gmail.com; ORCID ID: https://orcid.org/0009-0003-9514-0814. The author conducted the experiments, analyzed and visualized the data and prepared manuscript for submission.

Anna V. Epishkina, National Research Nuclear University MEPhI

Candidate of Medical Sciences, Associate Professor of Fundamental Medicine Department, MEPhI, Moscow, Russia; e-mail: afina-nn@mail.ru; ORCID ID: https://orcid.org/0000-0002-7824-7949. The author conducted the experiments on LLC and prepared the manuscript for submission.

Ekaterina A. Koreeva, National Research Nuclear University MEPhI

Postgraduate student, Fundamental Medicine Department, MEPhI, Moscow, Russia; e-mail: koreeva@yandex.ru; ORCID ID: https://orcid.org/0009-0009-4214-9974. The author conducted the experiments on LLC and wound healing and prepared the manuscript for submission.

Masud A. R. Farakhmand, National Research Nuclear University MEPhI

Postgraduate student, Fundamental Medicine Department, MEPhI, Moscow, Russia; e-mail: farahmand3@mail.ru; ORCID ID: https://orcid.org/0009-0009-6828-9078. The author conducted the experiments on wound healing and prepared the manuscript for submission.

Sergey P. Timoshkin, National Research Nuclear University MEPhI

Candidate of Medical Sciences, Associate Professor of Fundamental Medicine Department, MEPhI, Moscow, Russia; e-mail: timoshkin-sergej@list.ru; ORCID ID: https://orcid.org/0000-0001-5518-6859. The author conducted the experiments on wound healing and prepared the manuscript for submission.

Dmirty S. Blinov, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Doctor Habil. of Medical Sciences, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; e-mail: blinov-pharm@yandex.ru; ORCID ID: https://orcid.org/0000-0002-8385-4356. The author designed the project, provided consulting support, and, finally, revised the manuscript.

Evgenia V. Shikh, Sechenov University

Doctor Habil. of Medical Sciences, Head of Clinical Pharmacology and Internal Disease Department, Sechenov University, Moscow, Russia; e-mail: chih@mail.ru; ORCID ID: https://orcid.org/0000-0001-6589-7654. The author analyzed the obtained data and supervised the project.