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Triton modified polyethyleneimine conjugates assembled with growth arrest-specific protein 6 for androgenetic alopecia transdermal gene therapy.

ABSTRACT: Androgenetic alopecia is an androgen-dependent skin disorder that commonly affects hair follicle growth and hair loss. Gene therapy that can promote the proliferation and survival of hair follicle cells can be a potential choice for its cure. While transdermal application of therapeutic functional nucleic acids across the stratum corneum is quite difficult. Here, we first develop a transdermal agent for functional nucleic acid delivery using Triton X-100-modified low molecular weight polyethyleneimine (PEI-Triton-N, N = 6 or 8). In vitro cell experiments demonstrate that the PEI-Triton-N conjugates can stably encapsulate and efficiently deliver plasmid DNA to hard-to-transfect keratinocyte HaCaT cells. Further mouse model studies show that PEI-Triton-6 can encapsulate and deliver growth arrest-specific protein 6 (Gas6) plasmid through transdermal administration. The transfected Gas6 prolongs the anagen status, inhibits the apoptosis of hair follicle cells, and further promotes the proliferation and differentiation of hair follicle cells. The PEI-Triton-6/pDNA_Gas6 complexes can obviously alleviate hair loss in androgenetic alopecia mice and provides a promising strategy for gene therapy via transdermal administration.

SUBMITTER: Fan X

PROVIDER: S-EPMC9939716 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Triton modified polyethyleneimine conjugates assembled with growth arrest-specific protein 6 for androgenetic alopecia transdermal gene therapy.

Fan Xinli X Zhao Xiaoran X Xu Jianfei J Wang Jing J Wang Qian Q Tang Xinjing X

Materials today. Bio 20230202

Androgenetic alopecia is an androgen-dependent skin disorder that commonly affects hair follicle growth and hair loss. Gene therapy that can promote the proliferation and survival of hair follicle cells can be a potential choice for its cure. While transdermal application of therapeutic functional nucleic acids across the stratum corneum is quite difficult. Here, we first develop a transdermal agent for functional nucleic acid delivery using Triton X-100-modified low molecular weight polyethylen ...[more]

PMID: 36815198

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Project description:BackgroundAndrogenetic alopecia (AGA) is the most common form of hair loss. Studies have suggested a potential link to metabolic disorders, but with conflicting results. To elucidate the lipidomics profile and sex-specific variations in AGA, while exploring correlation between AGA and metabolic syndrome (MetS).MethodsThe AGA patients (n = 83) and healthy controls (n = 84) were collected in the study. The lipid profiles were analyzed using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Serum levels of important factors associated with AGA, namely dihydrotestosterone (DHT), prostaglandin D2 (PGD2) and transforming growth factor-β1 (TGF-β1) were quantified using ELISA.ResultsCompared with controls, AGA patients had a higher probability of MetS (26.51% vs 11.9%, P < 0.05). Fifty-one differentially expressed lipids were identified in AGA. The kind of triglyceride (TG) were significantly increased, while phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS) exhibited remarkable decrease. PC (16:2/21:6), PC (34:4p), PE (41:7), PE (44:12), PG (40:9), PI (32:2) and TG (15:0/18:1/18:1) were identified as potential biomarkers of AGA with the highest specificity. The levels of DHT, PGD2 and TGF-β1 were significantly elevated in AGA. All seven lipids showed significant correlations with DHT, PC (34:4p) and TG (15:0/18:1/18:1) were significantly associated with PGD2, TGF-β1 displayed exclusively correlation with TG (15:0/18:1/18:1) (all P < 0.05). Furthermore, these lipids were also significantly linked to systolic blood pressure and BMI, while some of them also showed significant associations with total cholesterol and HDL-C. In subgroups, forty-two differentially expressed lipids were identified in male AGA vs male control and eighty-one in female AGA vs female control. PC (16:2/21:6) was the only specific lipids common to both sexes.ConclusionsAberrant lipid metabolism was observed in AGA, with distinct lipidomic profiles between male and female AGA. The potential biomarkers were closely related to DHT, PGD2, TGF-β1 and MetS-related indicators. It provides the foundation for revealing the mechanisms of AGA.

Project description:BackgroundEarly-onset androgenetic alopecia (AGA) has been associated with various chronic conditions, including metabolic syndrome (MetS). Gaining a deep understanding of early-onset AGA may enable earlier intervention in individuals at high risks. This scoping review aims to explore the risk factors and etiology, associated conditions, and adverse effects on wellbeing in early-onset AGA.MethodsElectronic literature searches were conducted in MEDLINE, EMBASE and CENTRIAL. Eligible studies included case-control, cohort, cross-sectional, and meta-analysis studies. Selected studies needed to clearly define early-onset AGA cases or include only cases starting before the age of 40 and compare them with appropriate controls. The exclusion criteria comprised editorials, commentaries, case series, and non-systematic reviews, among others. Data extraction involved collecting study characteristics, methodologies, main outcomes, and findings. Descriptive tables were used to summarize key information and relevant variables when necessary.ResultsAmong the 65 eligible articles, 67.69% were case-control studies and 78.46% evaluated only male patients. "Early-onset" was defined as cases developing before the age of 30 years in 43.08% of the studies. The Hamilton-Norwood scale was the most frequently used method for evaluating the severity of alopecia in men (69.23%). Reported risk factors for early-onset AGA included a family history of AGA, cigarette smoking, unhealthy dietary habits, and a high body mass index. Early-onset AGA may also be associated with hormonal profiles, 5α-reductase enzyme activity, androgen receptor genes, and some susceptibility loci. Comorbidities investigated included MetS, cardiovascular disease, insulin resistance, dyslipidemia, and Parkinson's disease. Men with early-onset AGA may have reduced treatment efficacy with drug like rosuvastatin, metformin or lisinopril for dyslipidemia, prediabetes, or hypertension. Additionally, young men with AGA tended to suffer from psychological issues such as anxiety and low self-esteem compared to those without hair loss.ConclusionEarly-onset AGA is a complex condition with various risk factors and etiology, associated comorbidities, and potential implications for treatment response and psychological health.

Dataset Information

Triton modified polyethyleneimine conjugates assembled with growth arrest-specific protein 6 for androgenetic alopecia transdermal gene therapy.

Publications

Triton modified polyethyleneimine conjugates assembled with growth arrest-specific protein 6 for androgenetic alopecia transdermal gene therapy.

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