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Silicon-polysaccharide fluorescent nanocomposite for everolimus delivery and theranostic application in clear cell
Zhihong Lv1, Yuping Xu1, Huiying Liu1
1Oncology Department, Linfen People's Hospital, Linfen, Shanxi, China.
Abstract:
Everolimus showed therapeutic promise in treating clear cell renal cell carcinoma (ccRCC), yet its efficacy was limited by poor bioavailability and weak tumor targeting. In this study, we developed a multifunctional Co(II)-based MOF (CP1) using H4L and bpp ligands, forming a 3D (4,8)-connected framework. To enhance stability and functionality, CP1 was coated with sodium alginate (SA) and APTMS, and further modified with a fluorescent benzopyranone derivative (compound 1) via Ullmann-type coupling, yielding 1-SA-APTMS@CP1. The final nanocarrier, 1-SA-APTMS@CP1@EVE, exhibited a high surface area (98.3 m2/g), mesoporosity (2-6 nm), and strong structural integrity. It enabled dual-channel fluorescence detection of GSH and NAD(P)H, with detection limits of 233 pM and 65 nM, respectively. In vitro, the system effectively inhibited ccRCC cell proliferation and downregulated TNFRSF18, a key immunomodulatory gene. This study provides a redox-responsive, fluorescence-trackable delivery platform for everolimus, offering potential for targeted and immune-synergistic therapy in ccRCC.
Insights
This study developed a novel nanocarrier for everolimus, improving its delivery for clear cell renal cell carcinoma (ccRCC) treatment. The system offers targeted therapy and immune synergy, enhancing therapeutic potential.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Clear cell renal cell carcinoma (ccRCC) treatment with everolimus is limited by poor bioavailability and tumor targeting.
- Development of advanced drug delivery systems is crucial for improving ccRCC therapy.
Purpose of the Study:
- To develop a multifunctional nanocarrier for enhanced delivery of everolimus in ccRCC.
- To create a redox-responsive, fluorescence-trackable platform for targeted and immune-synergistic ccRCC therapy.
Main Methods:
- Fabrication of a Co(II)-based MOF (CP1) using H4L and bpp ligands.
- Coating CP1 with sodium alginate (SA) and APTMS, followed by modification with a fluorescent benzopyranone derivative.
- Loading everolimus (EVE) onto the modified nanocarrier to create 1-SA-APTMS@CP1@EVE.
Main Results:
- The nanocarrier 1-SA-APTMS@CP1@EVE exhibited high surface area (98.3 m²/g) and mesoporosity (2-6 nm).
- The system enabled dual-channel fluorescence detection of GSH and NAD(P)H with low detection limits.
- In vitro studies showed inhibition of ccRCC cell proliferation and downregulation of TNFRSF18.
Conclusions:
- The developed nanocarrier provides a stable, functional platform for everolimus delivery.
- This system offers potential for targeted and immune-synergistic therapy in ccRCC.
- The fluorescence-trackable nature aids in monitoring drug delivery and therapeutic response.
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