Reactive Oxygen Species-Mediated Inflammation and Apoptosis in Hand-Foot Syndrome Induced by PEGylated Liposomal Doxorubicin
Open accessAbstract
BACKGROUND: (PEGylated liposomal doxorubicin, PLD) has been widely used in cancer treatment due to its excellent therapeutic efficacy, but it can simultaneously cause severe adverse effects such as hand-foot syndrome (HFS). To date, the pathophysiologic mechanism of HFS development induced by PLD administration has not been well understood. MATERIALS AND METHODS: The histological features of skin lesion in PLD-induced HFS model were characterized by hematoxylin and eosin (H&E) staining and picrosirius red staining, and the induction of inflammation and apoptosis in the epidermal layer was detected by immunohistochemical and TUNEL staining. Moreover, the generation of reactive oxygen species (ROS) was determined to elucidate the potential mechanism of skin lesion in the development of HFS. RESULTS: The administration of PLD has been demonstrated to induce the histological damage of skin tissues including the destruction of collagen fibers and the induction of severe inflammation and apoptosis of epidermal cells. The mechanism was probably attributed to the accumulation of PLD in the skin tissues during the long-term circulation and further the induction of ROS to cause the oxidative damage of keratinocytes owing to the sustained release of doxorubicin from PLD. CONCLUSION: The ROS generation induced by the administration of PLD has been identified to be a crucial factor in the development of HFS, which could be used as a potential therapeutic target to alleviate the HFS symptom of PLD administration.
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Keratinocytes are often targeted during chemotherapy, and necrosis of keratinocytes has been reported.
“In addition, keratinocytes are often targeted during chemotherapy, and necrosis of keratinocytes has been reported47.”
From Morphological characteristics and notes of the skin in preclinical toxicity assessment (2023) · cites this paper as [47]
The Results and Discussion section (page unavailable) reports that doxorubicin and PEGylated liposomal doxorubicin caused keratinocyte apoptosis, supporting chemotherapy-related keratinocyte damage. It does not report keratinocyte necrosis or establish that keratinocytes are often targeted across chemotherapy treatments. (LLM, conf=0.87)
Experimental — accuracy not yet measuredDOX is a cytotoxic drug which suffers from severe side effects such as cardiotoxicity.
“Previous studies have confirmed that DOX is a cytotoxic drug which suffered from severe side effects such as cardiotoxicity.58–60”
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Cites
Doxil® — The first FDA-approved nano-drug: Lessons learned
Barenholz, Y. (. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.03.020 · Cited by 4,792 · see citing works
Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia (‘hand-foot’ syndrome)
Lorusso, D., Stefano, A. D., Carone, V., Fagotti, A., Pisconti, S., & Scambia, G. (2007) · Annals of Oncology · doi:10.1093/annonc/mdl477 · Cited by 263 · see citing works
New insights and evolving role of pegylated liposomal doxorubicin in cancer therapy
Gabizón, A., Patil, Y. P., & La-Beck, N. M. (2016) · Drug Resistance Updates · doi:10.1016/j.drup.2016.10.003 · Cited by 251 · see citing works
Miller, K. K., Gorcey, L., & McLellan, B. N. (2014) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2014.03.019 · Cited by 229 · see citing works
Nanomedicine applications in the treatment of breast cancer: current state of the art
Wu, D., Si, M., Xue, H.-Y., & Wong, H. L. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s123437 · Cited by 207 · see citing works
Ryu, Y. S., Kang, K. A., Piao, M. J., Ahn, M. J., Yi, J. M., Hyun, Y., Kim, S. H., Ko, M. K., Park, C. O., & Hyun, J. W. (2018) · Redox Biology · doi:10.1016/j.redox.2018.101080 · Cited by 147 · see citing works
Pelin, M., Fusco, L., Martín, C., Sosa, S., Frontiñán-Rubio, J., Gonzalez-Dominguez, J. M., Durán‐Prado, M., Vázquez, E., Prato, M., & Tubaro, A. (2018) · Nanoscale · doi:10.1039/c8nr02933d · Cited by 134 · see citing works
Pegylated liposomal doxorubicin in ovarian cancer.
Green, A. E., & Rose, P. G. (2006) · PubMed Central · Cited by 128 · see citing works
Zhao, Y., Alakhova, D. Y., Kim, J. O., Bronich, T. K., & Kabanov, A. V. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.02.026 · Cited by 125 · see citing works
Jacobi, U., Waibler, E., Schulze, P., Sehouli, J., Oskay-Özcelik, G., Schmook, T., Sterry, W., & Lademann, J. M. (2005) · Annals of Oncology · doi:10.1093/annonc/mdi204 · Cited by 114 · see citing works
Incidence and implications of chemotherapy related hand-foot syndrome
Nikolaou, V., Syrigos, K., & Saif, M. W. (2016) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2016.1238067 · Cited by 105 · see citing works
Pathogenesis of Hand-Foot Syndrome induced by PEG-modified liposomal Doxorubicin
横道, 憲., Nagasawa, T., Coler-Reilly, A. L. G., Suzuki, H., Kubota, Y., Yoshioka, R., Tozawa, A., Suzuki, N., & Yamaguchi, Y. (2013) · Human Cell · doi:10.1007/s13577-012-0057-0 · Cited by 98 · see citing works
Resolving The Nanoparticles Paradox
Donaldson, K. (2006) · Nanomedicine · doi:10.2217/17435889.1.2.229 · Cited by 94 · see citing works
Luanpitpong, S., Pithi Chanvorachote, B., Nimmannit, U., Leonard, S. S., Stehlik, C., Wang, L., & Rojanasakul, Y. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.03.010 · Cited by 92 · see citing works
Alibolandi, M., Abnous, K., Mohammadi, M., Hadizadeh, F., Sadeghi, F., Taghavi, S., Jaafari, M. R., & Ramezani, M. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.08.030 · Cited by 74 · see citing works
Pharmacokinetics and pharmacodynamics of liposomal chemophototherapy with short drug-light intervals
Luo, D., Carter, K. A., Molins, E. A. G., Straubinger, N. L., Geng, J., Shao, S., Jusko, W. J., Straubinger, R. M., & Lovell, J. F. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.01.030 · Cited by 70 · see citing works
He, H., Jiang, S., Xie, Y., Lü, Y., Qi, J., Dong, X., Zhao, W., Yin, Z., & Wu, W. (2018) · Nanoscale Horizons · doi:10.1039/c8nh00010g · Cited by 55 · see citing works
Cui, S., Fu, Y., Liu, Y., Kou, X., Zhang, J., Gan, Y., Zhou, Y., & Wang, X. (2019) · International Journal of Oral Science · doi:10.1038/s41368-018-0036-8 · Cited by 41 · see citing works
ROS‐challenged keratinocytes as a new model for oxidative stress‐mediated skin diseases
Barygina, V. V., Becatti, M., Lotti, T., Moretti, S., Taddei, N., & Fiorillo, C. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27485 · Cited by 40 · see citing works
Jia, J., Zhang, S., Wen, K., & Li, Q. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s210107 · Cited by 36 · see citing works
Self-citationAlimohammadi, R., Alibeigi, R., Nikpoor, A. R., Chalbatani, G. M., Webster, T. J., Jaafari, M. R., & Jalali, S. A. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s260760 · Cited by 27 · see citing works
Boers‐Sonderen, M. J., van Herpen, C. M. L., van der Graaf, W. T. A., Desar, I. M. E., van der Logt, M. G. W. A., de Beer, Y. M., Ottevanger, P. B., & van Erp, N. P. (2014) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-014-2514-9 · Cited by 19 · see citing works
Schmook, T., Jacobi, U., Lademann, J. M., Worm, M., & Stockfleth, E. (2005) · Dermatology · doi:10.1159/000083794 · Cited by 14 · see citing works
The role of the ATM/Chk/P53 pathway in mediating DNA damage in hand-foot syndrome induced by PLD
Yang, J., Qiao, L., Zeng, Z., Wang, J., Zhu, T., Wei, J., Wu, M., Ye, S., Huang, X., Ma, D., et al. (2016) · Toxicology Letters · doi:10.1016/j.toxlet.2016.11.024 · Cited by 12 · see citing works
Case series of docetaxel-induced dorsal hand–foot syndrome
Patel, J., Ringley, J. T., & Moore, D. C. (2018) · Therapeutic Advances in Drug Safety · doi:10.1177/2042098618776911 · Cited by 11 · see citing works
You, Zuo, L., & Li, W. S. (2010) · International Journal of Nanomedicine · doi:10.2147/ijn.s8488 · Cited by 10 · see citing works
A genipin-crosslinked protein–polymer hybrid system for the intracellular delivery of ribonuclease A
Liang, X., Tang, X., Yang, J., Zhang, J., Han, H., & Li, Q. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s210486 · Cited by 10 · see citing works
Self-citationChen, Y.-J., Lee, Y.-T., Wen, C., Chen, Y.-C., & Chen, Y. (2014) · OncoTargets and Therapy · doi:10.2147/ott.s63785 · Cited by 7 · see citing works
Hand-Foot Syndrome Related to Liposomal Doxorubicin
Swenson, K. K., & Bell, E. M. (2010) · Oncology nursing forum · doi:10.1188/10.onf.137-139 · Cited by 6 · see citing works
Discovery of skin lymphocytes was a game changer in experimental dermatology
Matos, T. R., & de Rie, M. A. (2017) · Experimental Dermatology · doi:10.1111/exd.13320 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Approved Nanomedicine against Diseases
Jia, Y., Jiang, Y., He, Y., Zhang, W., Zou, J., Magar, K. T., Boucetta, H., Teng, C., & He, W. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15030774 · Cited by 169 · see citing works
Anti-PEG antibodies: Current situation and countermeasures
Fu, J., Wu, E., Li, G., Wang, B., & Zhan, C. (2024) · Nano Today · doi:10.1016/j.nantod.2024.102163 · Cited by 114 · see citing works
Targeted Drug Delivery for the Treatment of Blood Cancers
Jiang, Y. X., Lin, W., & Zhu, L. (2022) · Molecules · doi:10.3390/molecules27041310 · Cited by 46 · see citing works
Liang, X., Wang, Y., Shi, H., Dong, M., Han, H., & Li, Q. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s304526 · Cited by 41 · see citing works
Self-citationDeng, X., Zhang, Z., Ren, T., & Chen, L. (2025) · Cancer Nanotechnology · doi:10.1186/s12645-025-00342-1 · Cited by 33 · see citing works
Morphological characteristics and notes of the skin in preclinical toxicity assessment
Moroki, T. (2023) · Journal of Toxicologic Pathology · doi:10.1293/tox.2022-0103 · Cited by 26 · see citing works
Engineering advanced nanomedicines against central nervous system diseases
Shi, S., Ren, H., Xie, Y., Yu, M., Chen, Y., & Yang, L. (2023) · Materials Today · doi:10.1016/j.mattod.2023.08.005 · Cited by 24 · see citing works
Zhai, L., Shi, Y., Yan, Y., Lu, A., Liu, X., Lei, L., Sun, Y., Jiang, L., Wang, X., Qian, H.-G., et al. (2023) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.108104 · Cited by 18 · see citing works
Juan, Z., Chen, J., Ding, B., Yongping, L., Cai, H., Chen, H., Wang, L., Le, Y., Shi, J., Wu, Y., et al. (2024) · International Journal of Surgery · doi:10.1097/js9.0000000000002147 · Cited by 13 · see citing works
Lian, J., Tang, X., Gui, Y., Lu, S., Song, Y., & Deng, Y. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.124659 · Cited by 11 · see citing works
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Li, X., Wang, L., Zhang, Y., Zhai, Y., Wang, L., Li, X., Wang, L., & Zhu, Y. (2023) · Colloids and Surfaces A Physicochemical and Engineering Aspects · doi:10.1016/j.colsurfa.2023.132504 · Cited by 7 · see citing works
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Panghal, A., & Flora, S. J. S. (2022) · Springer eBooks · doi:10.1007/978-3-031-12398-6_19 · Cited by 5 · see citing works
Kim, J. M., Choi, M., & Yang, J. H. (2023) · Molecules · doi:10.3390/molecules28041974 · Cited by 4 · see citing works
Mashaly, M. E., Kotb, H. M., Abdin, A. A., & Hedya, S. E. (2023) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2022-0439 · Cited by 4 · see citing works
dos Reis, F. C. G. P., de Menêses, A. G., Mazoni, S. R., Silveira, R. C. D. C. P., dos Reis, P. E. D., & Vasques, C. I. (2023) · Revista da Escola de Enfermagem da USP · doi:10.1590/1980-220x-reeusp-2023-0107en · Cited by 4 · see citing works
Quan, X., Li, J., Sun, J., Xing, X., Liu, D., Ji, H., & Guo, Q. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1564681 · Cited by 3 · see citing works
Darvin, M. E., Lademann, J. M., & Jung, S. (2024) · Anticancer Research · doi:10.21873/anticanres.16944 · Cited by 2 · see citing works
Li, Y., Qi, H., Geng, Y., Gao, J., & Cai, X. (2025) · Journal of drug targeting · doi:10.1080/1061186x.2025.2544806 · Cited by 2 · see citing works
Hirakata, M., Tomikawa, E., Sakai, C., Uchida, M., Okano, T., Shimozono, R., Kawai, M., Itaba, S., Munakata, L., Suzuki, R., et al. (2024) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2024.116912 · Cited by 2 · see citing works
Hand-foot syndrome, case presentation and literature review
Vargas-Hernández, V. M., & Vargas-Hernández, V. M. (2024) · Obstetrics & Gynecology International Journal · doi:10.15406/ogij.2024.15.00776 · Cited by 1 · see citing works
Dermatological impacts of urological cancer treatments
Sataray-Rodriguez, A., Oladinni, D., Adler, R., Doshi, N., Patrick, B., Aust, N., Sun, M., Schur, N., Jamieson, S., & Weiss, J. P. (2025) · World Journal of Urology · doi:10.1007/s00345-025-05896-8 · Cited by 1 · see citing works
Das, T., Ghosh, D., Karmakar, S., Bhar, S., Kar, K., Pandit, P., Chauhan, G., Mondal, S., & Chandra, A. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.109460 · Cited by 1 · see citing works
dos Reis, F. C. G. P., de Menêses, A. G., Mazoni, S. R., Silveira, R. C. D. C. P., dos Reis, P. E. D., & Vasques, C. I. (2023) · Revista da Escola de Enfermagem da USP · doi:10.1590/1980-220x-reeusp-2023-0107pt · Cited by 1 · see citing works
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Guo, N.-T., Ni, J., Wei, G.-L., & Huo, J. (2025) · World Chinese Journal of Digestology · doi:10.11569/wcjd.v33.i1.27
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Guo, N.-T., Ni, J., Wei, G.-L., & Huo, J. (2025) · World Chinese Journal of Digestology · doi:10.11569/wcjd.v33.i1.21
Wu, E., Ding, T., Yu, Y., Liu, M., Qian, J., & Zhan, C. (2026) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2026.03.027
Navarro-Beleño, K., & Castrillo, M. B. C. M. B. (2026) · International journal of research in medical and clinical science. · doi:10.70829/ijrmcs.v04.i01.016
Huang, R., Zhang, Y., Yang, M., Guo, J., Wang, Y., Hou, D., Wu, Q., & Wang, S. (2026) · Langmuir · doi:10.1021/acs.langmuir.6c01515
Shetake, N. G., Ali, M., Kumar, A., Manojkumar, V., Chavan, N., Gota, V., & Pandey, B. N. (2026) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2026.108571
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Mikito, H., ミキト, ヒ., & Mikito, H. (2026) · Institutional Repositories DataBase (IRDB) · doi:10.15068/0002024850
Ma, Y., Zhao, J., Lian, J., Zhang, K., Zang, C., Li, H., Du, Z., Ding, K., Liu, X., Song, Y., et al. (2026) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2026.108818
- Authors
- Hu, X., Dong, M., Liang, X., Liu, Z., & Li, Q.
- Affiliations
- Jilin University (CN)
- First Hospital of Jilin University (CN)
- Corresponding author
- Li, Quanshun
- Venue
- International Journal of Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2021-01
- Volume
- Volume 16
- Pages
- 471-480
- ISSN
- 1176-9114 (ISSN-L)
- 1178-2013
- PMC
- PMC7822082
- OpenAlex
- W3123377942
- Cited by
- 29
- References
- 30
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 3 · 2021: 1
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Nanomedicine (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- National Natural Science Foundation of China (81872928, 81673502)
- People's Government of Jilin Province (SXGJQY2017-4)
- Education Department of Jilin Province (JJKH20190010KJ)
- Topics
- Health Sciences › Medicine › Dermatology › Chemotherapy-related skin toxicity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- hand-foot syndrome, pegylated liposomal doxorubicin, reactive oxygen species, oxidative stress, keratinocyte apoptosis, skin inflammation, skin histopathology, sustained drug release, chemotherapy side effects, epidermal cells
- MeSH terms
- HaCaT Cells, Animals, Antibiotics, Antineoplastic, Disease Models, Animal, Doxorubicin, Female, Humans, Inflammation, Polyethylene Glycols, Skin, Keratinocytes, Interleukin-6, Rats, Wistar, Apoptosis, Reactive Oxygen Species, Rats, Interleukin-1beta, Hand-Foot Syndrome
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