Osteopromotive PDA-modified gold nanoparticles-incorporated bioinspired polycaprolactone-based nanofibers for bone cancer therapy and robust bone regeneration

Abstract

The limited efficacy of traditional therapies for bone cancer and related bone defects led to the instigation of new bifunctional therapies. In this work, polydopamine (PDA) coated gold nanospheres (GNSs) were integrated into polycaprolactone (PCL) to fabricate bifunctional randomly oriented PCL-GNSs@PDA nanofibrous composite scaffolds and applied for photothermal bone cancer therapy and robust bone tissue regeneration. GNSs (30 nm sized) were coated with a uniform 10 nm layer of PDA, and the resulting GNSs@PDA core-shell nanoparticles were incorporated in three different concentrations (1.5, 3.0, and 5.0 mg) in PCL-based random nanofibers. The integration of GNSs@PDA nanoparticles enhanced electric conductivity, surface area, elasticity, compressive strength, photothermal properties as well as biocompatibility, photo-activity, and protein absorption of synthesized PCL-GNSs@PDA composite nanofibers which played a crucial role on its bifunctionality. Random-oriented PCL-GNSs@PDA (5.0 mg) nanofibrous scaffold showed superior photothermal activity which led to 94 % of bone cancer cell (MG-63 cells) ablation by maximum cell alteration and damaged cytoskeleton at low NIR light power (0.5 W/cm²) irradiation for 5 min. FACS analysis after 24 hours also displayed a higher percentage of apoptosis (60.2 %) in comparison to pure PCL (7.5 %) suggesting that PCL-GNSs@PDA (5.0 mg) induced highly efficient apoptosis in MG-63 cells. Also, PCL-GNSs@PDA (5.0 mg) showed higher cell proliferation, excellent cytocompatibility, and optimal cell adhesion for bone tissue (MC3T3-E1 cells) regeneration after 21-days as suggested by ALP, ARS, von Kossa staining, and qRT-PCR results. Bifunctional PCL-GNSs@PDA showed great potential as osteopromotive and bioinspired nanocomposite tissue engineering scaffolds for highly efficient bone cancer phototherapy and bone reconstruction.