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Engineering tanshinone-loaded, levan-biofunctionalized polycaprolactone nanofibers for treatment of skin cancer
Salma E El-Habashy1, Amal H El-Kamel1, Radwa A Mehanna2
1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Abstract:
Skin cancer is a challenging condition of the highest prevalence rate among other types of cancer. Thus, advancement of local therapeutic approaches for skin cancer is highly needed. Recently, the use of phytotherapeutics, like tanshinone IIA (Tan), as anticancer agents has become promising. In this work, we engineered Tan-loaded polycaprolactone nanofibers, biofunctionalized with levan and egg-lecithin (Tan@Lev/EL/PCL-NF) for local skin cancer therapy. Novel Tan@Lev/EL/PCL-NF were prepared using w/o-emulsion electrospinning, employing a 23-factorial design. Composite NF exhibited nanofiber diameter (365.56 ± 46.25 nm), favorable surface-hydrophilicity and tensile strength. Tan@Lev/EL/PCL-NF could achieve favorably controlled-release (100% in 5 days) and Tan skin-deposition (50%). In vitro anticancer studies verified prominent cytotoxicity of Tan@Lev/EL/PCL-NF on squamous-cell-carcinoma cell-line (SCC), with optimum cytocompatibility on fibroblasts. Tan@Lev/EL/PCL-NF exerted high apoptotic activity with evident nuclear fragmentation, G2/M-mitosis cell-cycle-arrest and antimigratory efficacy. In vivo antitumor activity was established in mice, confirming pronounced inhibition of tumor-growth (224.25 ± 46.89%) and relative tumor weight (1.25 ± 0.18%) for Tan@Lev/EL/PCL-NF compared to other groups. Tan@Lev/EL/PCL-NF afforded tumor-biomarker inhibition, upregulation of caspase-3 and knockdown of BAX and MKi67. Efficient anticancer potential was further confirmed by histomorphometric analysis. Our findings highlight the promising anticancer functionality of composite Tan@Lev/EL/PCL-NF, as efficient local skin cancer phytotherapy.
Insights
This study developed novel tanshinone IIA (Tan)-loaded nanofibers for skin cancer therapy. The engineered nanofibers demonstrated significant in vitro and in vivo anticancer activity, offering a promising phytotherapeutic approach.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Dermatology
Background:
- Skin cancer presents a high prevalence, necessitating advancements in local therapeutic strategies.
- Phytotherapeutics, such as tanshinone IIA (Tan), show potential as anticancer agents.
- Developing effective local therapies for skin cancer remains a critical unmet need.
Purpose of the Study:
- To engineer and characterize tanshinone IIA (Tan)-loaded polycaprolactone nanofibers biofunctionalized with levan and egg-lecithin (Tan@Lev/EL/PCL-NF) for local skin cancer treatment.
- To evaluate the in vitro and in vivo anticancer efficacy of the developed nanofiber system.
Main Methods:
- Tan-loaded polycaprolactone nanofibers were fabricated using w/o-emulsion electrospinning with a 2³-factorial design.
- Characterization included assessment of nanofiber diameter, surface hydrophilicity, and tensile strength.
- In vitro cytotoxicity, apoptosis, cell-cycle arrest, and antimigratory effects were evaluated on cancer cells and fibroblasts. In vivo antitumor activity was assessed in a mouse model.
Main Results:
- The composite nanofibers (Tan@Lev/EL/PCL-NF) exhibited controlled release (100% in 5 days) and significant skin deposition (50%).
- In vitro studies showed potent cytotoxicity against squamous-cell carcinoma (SCC) with optimal cytocompatibility on fibroblasts, inducing apoptosis and cell-cycle arrest.
- In vivo studies demonstrated significant inhibition of tumor growth (224.25 ± 46.89%) and tumor weight, alongside modulation of key tumor biomarkers.
Conclusions:
- The developed Tan@Lev/EL/PCL-NF system demonstrates promising anticancer functionality for local skin cancer phytotherapy.
- The composite nanofibers effectively inhibit tumor growth and biomarkers, highlighting their therapeutic potential.
- This engineered nanofiber system represents an efficient and advanced approach for treating skin cancer.
