Repair and reconstruction of a resected tumor defect using a composite of tissue flap-nanotherapeutic-silk fibroin and chitosan scaffold.

A multifaceted strategy using a composite of anti-cancer nanotherapeutic and natural biomaterials silk fibroin (SF) and chitosan (CS) blend scaffolds was investigated for the treatment of a tissue defect post-tumor resection by providing local release of the therapeutic and filling of the defect site with the regenerative bioscaffolds. The scaffold-emodin nanoparticle composites were fabricated and characterized for drug entrapment and release, mechanical strength, and efficacy against GILM2 breast cancer cells in vitro and in vivo in a rat tumor model. Emodin nanoparticles were embedded in SF and SFCS scaffolds and the amount of emodin entrapment was a function of the scaffold composition and emodin loading concentration. In vitro, there was a burst release of emodin from all scaffolds during the first 2 days though it was detected even after 24 days. Increase in emodin concentration in the scaffolds decreased the overall elastic modulus and ultimate tensile strength of the scaffolds. After 6 weeks of in vivo implantation, the cell density (p < 0.05) and percent degradation (p < 0.01) within the remodeled no emodin SFCS scaffold was significantly higher than the emodin loaded SFCS scaffolds, although there was no significant difference in the amount of collagen deposition in the regenerated SFCS scaffold. The presence and release of emodin from the SFCS scaffolds inhibited the integration of SFCS into the adjacent tumor due to the formation of an interfacial barrier of connective tissue that was lacking in emodin-free SFCS scaffolds. While no significant difference in tumor size was observed between the in vivo tested groups, tumors treated with emodin loaded SFCS scaffolds had decreased presence and size and similar regeneration of new tissue as compared to no emodin SFCS scaffolds.

Fabrication and characterization of silk fibroin-derived curcumin nanoparticles for cancer therapy.

Biologically derived nanoparticles (<100 nm) were fabricated for local and sustained therapeutic curcumin delivery to cancer cells. Silk fibroin (SF) and chitosan (CS) polymers were blended noncovalently to encapsulate curcumin in various proportions of SF and CS (75:25, 50:50, and 25:75 SF:CS) or pure SF at two concentrations (0.1% w/v and 10% w/v) using the devised capillary-microdot technique. Curcumin-polymer conjugates were frozen, lyophilized, crystallized, suspended in phosphate-buffered saline for characterization, and tested for efficacy against breast cancer cells. All nanoparticle formulations except 0.1% w/v 50:50 SFCS were less than 100 nm in size as determined with the transmission electron microscopy. The entrapment and release of curcumin over eight days was highest for SF-derived nanoparticles as compared to all SFCS blends. The uptake and efficacy of SF-coated curcumin was significantly higher (p < 0.001) than SFCS-coated curcumin in both low and high Her2/neu expressing breast cancer cells. Interestingly, the uptake of curcumin was highest for the high Her2/neu expressing breast cancer cells when delivered with a 10% w/v SF coating as compared to other formulations. In conclusion, SF-derived curcumin nanoparticles show higher efficacy against breast cancer cells and have the potential to treat in vivo breast tumors by local, sustained, and long-term therapeutic delivery as a biodegradable system.