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Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells
Yasaman Hamedani1, Samik Chakraborty2,3, Akash Sabarwal2,3
1Department of Mechanical Engineering, Biomedical Engineering and Biotechnology Program, University of Massachusetts Dartmouth, Dartmouth, MA, United States of America.
Abstract:
Renal Cell Carcinoma (RCC) often becomes resistant to targeted therapies, and in addition, dose-dependent toxicities limit the effectiveness of therapeutic agents. Therefore, identifying novel drug delivery approaches to achieve optimal dosing of therapeutic agents can be beneficial in managing toxicities and to attain optimal therapeutic effects. Previously, we have demonstrated that Honokiol, a natural compound with potent anti-tumorigenic and anti-inflammatory effects, can induce cancer cell apoptosis and inhibit the growth of renal tumors in vivo. In cancer treatment, implant-based drug delivery systems can be used for gradual and sustained delivery of therapeutic agents like Honokiol to minimize systemic toxicity. Electrospun polymeric fibrous scaffolds are ideal candidates to be used as drug implants due to their favorable morphological properties such as high surface to volume ratio, flexibility and ease of fabrication. In this study, we fabricated Honokiol-loaded Poly(lactide-co-glycolide) (PLGA) electrospun scaffolds; and evaluated their structural characterization and biological activity. Proton nuclear magnetic resonance data proved the existence of Honokiol in the drug loaded polymeric scaffolds. The release kinetics showed that only 24% of the loaded Honokiol were released in 24hr, suggesting that sustained delivery of Honokiol is feasible. We calculated the cumulative concentration of the Honokiol released from the scaffold in 24hr; and the extent of renal cancer cell apoptosis induced with the released Honokiol is similar to an equivalent concentration of direct application of Honokiol. Also, Honokiol-loaded scaffolds placed directly in renal cell culture inhibited renal cancer cell proliferation and migration. Together, we demonstrate that Honokiol delivered through electrospun PLGA-based scaffolds is effective in inhibiting the growth of renal cancer cells; and our data necessitates further in vivo studies to explore the potential of sustained release of therapeutic agents-loaded electrospun scaffolds in the treatment of RCC and other cancer types.
Insights
Novel electrospun scaffolds deliver Honokiol effectively, inhibiting renal cancer cell growth and migration. This sustained drug delivery approach shows promise for treating renal cell carcinoma (RCC) and other cancers.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Drug Delivery Systems
Background:
- Renal Cell Carcinoma (RCC) exhibits resistance to targeted therapies, and dose-dependent toxicities limit treatment effectiveness.
- Honokiol, a natural compound, demonstrates anti-tumorigenic and anti-inflammatory properties, inducing cancer cell apoptosis and inhibiting renal tumor growth.
- Implant-based drug delivery systems offer sustained release of therapeutic agents, minimizing systemic toxicity and optimizing therapeutic effects.
Purpose of the Study:
- To fabricate and evaluate Honokiol-loaded Poly(lactide-co-glycolide) (PLGA) electrospun scaffolds for sustained drug delivery.
- To assess the structural characteristics and biological activity of these novel drug delivery systems.
- To investigate the efficacy of Honokiol delivered via electrospun scaffolds in inhibiting renal cancer cell proliferation, migration, and inducing apoptosis.
Main Methods:
- Fabrication of Honokiol-loaded PLGA electrospun scaffolds.
- Structural characterization using Proton Nuclear Magnetic Resonance (NMR).
- Evaluation of Honokiol release kinetics and biological activity in renal cancer cell cultures.
Main Results:
- Proton NMR confirmed the successful incorporation of Honokiol into the PLGA scaffolds.
- Release kinetics demonstrated sustained Honokiol delivery, with only 24% released in 24 hours.
- Honokiol released from scaffolds induced apoptosis in renal cancer cells similarly to direct application and inhibited cell proliferation and migration.
Conclusions:
- Honokiol delivered through electrospun PLGA scaffolds effectively inhibits renal cancer cell growth.
- Sustained release of therapeutic agents via electrospun scaffolds is feasible and warrants further in vivo investigation for RCC treatment.
- This approach holds potential for treating RCC and other cancer types by optimizing drug delivery and minimizing toxicity.
