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.
Highlights
Solid tumors of the kidney are collectively known as Kidney Cancer or Renal Cell Carcinoma (RCC); and it is among the 10 most frequently diagnosed cancers in the United States [1]
Novel Honokiol-eluting Poly Lactide -co-glycolide acid (PLGA)-based scaffold restricts renal cancer growth high voltage is applied to the tip of the capillary, the drop is stretched until a point where the electrostatic forces balance out the surface tension of the drop, forming a cone at the tip of the needle, known as Taylor cone
We have reported that Honokiol-induced renal cancer cell apoptosis is associated with the decreased expression of antiapoptotic proteins Bcl-2 and Bcl-xL and cytoprotective HO-1; and we checked whether the released Honokiol can modulate the expression of these intracellular molecules [5, 6]
Summary
Solid tumors of the kidney are collectively known as Kidney Cancer or Renal Cell Carcinoma (RCC); and it is among the 10 most frequently diagnosed cancers in the United States [1]. Renal cancer cells are dependent on Receptor Tyrosine Kinases (RTK) like c-MET for their survival and RTK targeted therapeutics (like, sorafenib, sunitinib, cabozantinib and others) are being used in the first-line of treatment of RCC [2,3,4]. Dose-dependent toxicity is a major hurdle in the clinical use of RTK targeted therapeutics (like c-MET inhibitor cabozantinib), subduing the anti-tumor effects of RTK inhibitor therapy [3]. Important is to explore new methods to deliver anti-tumor agents to mitigate dose-dependent toxicity. Our recent reports suggest that Honokiol exhibits anti-tumor properties against renal cancer cells and, studying novel delivery methods of Honokiol can be significant in exploring Honokiol as novel treatment of RCC [5, 6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
