Localization of Liposomes Containing a DNA Repair Enzyme in Murine Skin
Open accessAbstract
T4N5 liposomes, which contain the DNA repair enzyme T4 endonuclease V, were applied to mouse skin in vivo and added to cultured murine keratinocytes in vitro. The fate of the liposome membrane was followed using a fluorescent, lipophilic dye, and the fate of the enzyme was traced by immunogold labeling, followed by brightfield, fluorescence, or transmission electron microscopy. In vivo, T4N5 liposomes penetrated the stratum corneum, localized in epidermis and appendages of the skin, and were found inside basal keratinocytes. The enzyme was found inside keratinocytes treated in vitro and in the epidermis, hair follicles, and sebaceous glands of topically treated skin. Ultrastructural studies demonstrated the presence of liposomes in the cytoplasm of cells in the epidermis often concentrated in a perinuclear location. The enzyme was present in both nucleus and cytoplasm of keratinocytes and Langerhans cells. Liposomes were found in cells of the lymph nodes draining the site of contact sensitization, in association with topically applied antigen. The results demonstrate that liposomes can deliver encapsulated proteins into cells of the skin in vivo and provide insight into how liposome-enhanced DNA repair reduces UV-induced skin cancer and systemic immunosuppression in mice.
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Delivery of T4-pdg in mouse models increased the rate of CPD removal, reduced the frequency of SCC, and minimized UVB-induced immune suppression.
“Delivery of T4-pdg in mouse models increased the rate of CPD removal, reduced the frequency of SCC, and minimized UVB-induced immune suppression.”
From Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways (2018) · cites this paper as [15]
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Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways
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- Authors
- Yarosh, D., Bucana, C., Cox, P. A. T., Alas, L., Kibitel, J., & Kripke, M.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Yarosh, Daniel
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 1994-10
- Volume
- 103
- Issue
- 4
- Pages
- 461-468
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2093390384
- Cited by
- 142
- References
- 17
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 3 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 8 · 2015: 3 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 9.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA-52457, CA-16672, R01CA052457, P30CA016672)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- liposomes, T4 endonuclease V, DNA repair enzymes, topical drug delivery, skin, keratinocytes, stratum corneum penetration, epidermis, hair follicle, sebaceous glands, Langerhans cells, immunogold labeling, UV-induced skin cancer, immunosuppression, skin sensitization, lymph nodes
- MeSH terms
- Animals, Cell Movement, Endodeoxyribonucleases, Female, Liposomes, Mice, Inbred BALB C, Mice, Inbred C3H, Microscopy, Electron, DNA Ligases, Radiation-Protective Agents, Skin, Viral Proteins, Keratinocytes, Deoxyribonuclease (Pyrimidine Dimer), Mice
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