ABSTRACT
PURPOSE: To deliver insoluble natural compounds into colon cancer cells in a controlled fashion. MATERIALS AND METHODS: Curcumin (CM)-silk fibroin (SF) nanoparticles (NPs) were prepared by solution-enhanced dispersion by supercritical CO2 (SEDS) (20 MPa pressure, 1:2 CM:SF ratio, 1% concentration), and their physicochemical properties, intracellular uptake efficiency, in vitro anticancer effect, toxicity, and mechanisms were evaluated and analyzed. RESULTS: CM-SF NPs (<100 nm) with controllable particle size were prepared by SEDS. CM-SF NPs had a time-dependent intracellular uptake ability, which led to an improved inhibition effect on colon cancer cells. Interestingly, the anticancer effect of CM-SF NPs was improved, while the side effect on normal human colon mucosal epithelial cells was reduced by a concentration of ~10 µg/mL. The anticancer mechanism involves cell-cycle arrest in the G0/G1 and G2/M phases in association with inducing apoptotic cells. CONCLUSION: The natural compound-loaded SF nanoplatform prepared by SEDS indicates promising colon cancer-therapy potential.
Subject(s)
Carbon Dioxide/chemistry , Colonic Neoplasms/drug therapy , Fibroins/chemistry , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Death/drug effects , Colonic Neoplasms/pathology , Curcumin/administration & dosage , Curcumin/pharmacology , Curcumin/therapeutic use , Endocytosis/drug effects , HCT116 Cells , Humans , Nanoparticles/ultrastructure , Particle SizeABSTRACT
The development of more effective cancer therapeutic strategies are still critically required. The maximization of the therapeutic effect in combination with avoiding the severe side effects on normal tissues when using chemotherapy drugs is still an urgent problem that requires improvements urgently. Here we provide implantable and controllable drug-release that utilises silk fibroin (SF) as a nanofibrous drug delivery system (DDS) for cancer treatment. A nanofibrous structure with controllable fibre diameter (<100 nm) was produced. The drug release rate of the SF DDS was controlled by applying a post-treatment process. In vitro anti-cancer (HCT116) results indicated that curcumin (CM)-SF nanofibrous matrix had a superior anti-cancer potential when the concentration was >5 µg/mL. The mechanism could be explained by the cell cycle being held in the S phase. The toxic effect on normal cells (NCM460) was minimized by using a treatment concentration range (5-20 µg/mL). Implantation of this DDS into the tumour site inhibited the growth of solid tumour; this offers an alternative approach for novel cancer therapy.