ProtocolsMussel-inspired poly(L-DOPA)-templated mineralization for calcium phosphate-assembled intracellular nanocarriers

•DOX-loaded mineralized nanoparticles were prepared by a mineralization process.•The stability of CaP-mineralized polymer nanoparticles is enhanced.•The DOX-loaded mineralized nanoparticles trigger DOX release at endosomal pH.•CaP-mineralized polymer nanoparticles efficiently delivery DOX into cell nuclei.

We developed a calcium phosphate (CaP)-assembled polymer nanocarrier for intracellular doxorubicin (DOX) delivery based on a mussel-inspired mineralization approach. A DOX-loaded core-shell polymer nanoparticle (DOX-NP) consisting of a poly(3,4-dihydroxy-l-phenylalanine) (PDOPA) core and a poly (ethylene glycol) (PEG) shell was utilized as a nanotemplate for CaP mineralization. The mean hydrodynamic diameter of the DOX-loaded CaP-mineralized polymer nanoparticles (DOX-CaP-NPs) was 154.3 nm. Energy-dispersive X-ray spectroscopy confirmed that the DOX-CaP-NPs contained substantial amounts of Ca and P, elements found only in the CaP mineral. The loading efficiency and content of DOX, estimated by fluorescence spectroscopy, were 54.0% and 10.8 wt%, respectively. The CaP deposited in the PDOPA core domain enabled the DOX-CaP-NPs to maintain a robust structure and effectively inhibit DOX release at extracellular pH, whereas at endosomal pH, the CaP core dissolved to trigger a facilitated DOX release. The DOX-CaP-NPs may serve as robust nanocarriers with a high delivery efficacy for cancer chemotherapy.

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