Silk Fibroin Nanoparticle Functionalization with Arg-Gly-Asp Cyclopentapeptide Promotes Active Targeting for Tumor Site-Specific Delivery

Abstract

Arg-Gly-Asp (RGD)-based cyclopentapeptides (cRGDs) have a high affinity towards integrin αvβ3 and αvβ5, which are overexpressed by many tumor cells. Here, curcumin-loaded silk fibroin nanoparticles (SFNs) have been functionalized on the surface with cRGD to provide active targeting towards tumor cells; a “click reaction” between the RGD-based cyclopentapeptide carrying an azide group and triple-bond-functionalized nanoparticles has been exploited. Both naked and functionalized SFNs were less than 200 nm in diameter and showed a round-shaped morphology but, after functionalization, SFNs increased in size and protein molecular weight. The functionalization of SFNs’ surfaces with cRGD provided active internalization by cells overexpressing integrin receptors. At the lowest concentration tested (0.01 mg/mL), functionalized SFNs showed more effective uptake with respect to the naked by tumor cells that overexpress integrin receptors (but not for non-overexpressing ones). In contrast, at higher concentrations, the non-specific cell membrane protein–particle interactions are promoted and coupled to specific and target mediated uptake. Visual observations by fluorescence microscopy suggested that SFNs bind to integrin receptors on the cell surface and are then internalized by endocytosis. Overall, SFN functionalization provided in vitro active targeting for site-specific delivery of anticancer drugs, boosting activity and sparing healthy organs.

Protein nanoparticles directed cancer imaging and therapy

“…Integrin is overexpressed on many tumor cells. Bari et al [ 148 ] prepared silk fibroin nanoparticles and modified cyclopentapeptides (cRGDs) on their surface, which had a high affinity for integrin αvβ3 and αvβ5. The targeting peptide significantly increased the particle internalization into human urinary bladder (ECV) cancer cells.…”

Silk fibroin‐based films in food packaging applications: A review

“…Silk nanostructured materials are also one of the most promising bionanomaterials in the 21st century. They are generated from natural animal‐based protein polymer and used in various industries, such as drug delivery and medical application (Bari et al., 2021; Y. Ma et al., 2020; Z. Xu et al., 2019). Nowadays, composite SF nanoparticles have also been used in food packaging, including chitosan reinforced with SF nanodiscs (Ghosh et al., 2021), PLA incorporated with SF and yerba mate nanoparticles (Beltrán, Arrieta, et al., 2021), and PLA–PCL blend reinforced with SF nanoparticles (Chomachayi et al., 2021).…”

“…Silk nanostructured materials are also one of the most promising bionanomaterials in the 21st century. They are generated from natural animal-based protein polymer and used in various industries, such as drug delivery and medical application (Bari et al, 2021;Z. Xu et al, 2019).…”

Biomaterials for Soft Tissue Repair and Regeneration: A Focus on Italian Research in the Field

“…Silk fibroin nanoparticles improved the bioavailability of hydrophobic drugs and reduced the toxicity of many bioactive agents [ 57 , 58 , 59 ]. Furthermore, SF nanoparticles could be functionalized to obtain smart drug delivery systems; this approach allowed to obtain site-specific delivery of anticancer drugs, boosting activity and sparing healthy organs [ 60 ]. Addition of SF nanoparticles to 3D scaffolds represents a good strategy to obtain more efficient systems for tissue engineering applications.…”