Co-delivery of curcumin and si-STAT3 with a bioinspired tumor homing for polydopamine nanoparticles for synergistic osteosarcoma therapy

Abstract

Abstract Purpose Owing to the complexity of cancer, a synergistic combination of chemotherapy and gene therapy can be a promising therapeutic strategy. This study aimed to use stem cell membrane (SCM)-camouflaged polydopamine nanoparticles for simultaneous delivery of curcumin (CUR) and siRNA-targeting STAT3 (CPDA/siSTAT3@SCM NPs) for osteosarcoma (OS). Methods Transmission electron microscopy, UV–Vis absorbance spectra, zeta potential, cell co-localization, and Coomassie bright blue staining were used to characterize CPDA/siSTAT3@SCM NPs constructed by the self-assembly method. Drug release, cellular uptake, cell proliferation, apoptosis, wound healing, and transwell assays were evaluated in vitro. The expression levels of epithelial–mesenchymal transition (EMT)- and apoptosis-related proteins were measured by western blotting. Furthermore, the biodistribution, antitumor efficacy, and biosafety of CPDA/siSTAT3@SCM NPs in an MG63 xenograft mouse model were evaluated. Results CPDA/siSTAT3@SCM NPs were successfully synthesized to deliver CUR and siRNA simultaneously, and they showed osteosarcoma-targeting ability. Furthermore, it showed high cellular uptake and excellent synergistic antitumor effects in vitro. CPDA/siSTAT3@SCM NPs suppressed OS cell proliferation, migration, invasion, and EMT progression, and promoted the apoptotic process. In tumor-bearing mice, the treatment with CPDA/siSTAT3@SCM NPs showed an excellent antitumor effect with no side effects in major organs. Conclusion This study revealed that CPDA/siSTAT3@SCM NPs can target drug delivery by biomimetic multifunctional nanoparticles to treat OS through chemo-gene combined therapy.

Keywords

• MSC membrane camouflage
• Antitumor efficacy
• Epithelial–mesenchymal transition
• Stem cell membrane
• Targeted therapy