Fabrication of core/shell/shell structure nanoparticle with anticancer drug and dual-photosensitizer co-loading for synergistic chemotherapy and photodynamic therapy

A core/shell/shell structure nanoparticle with anticancer drug and dual-photosensitizer co-loading for synergistic chemotherapy and photodynamic therapy was developed. The nanoparticle contains an upconversion nanoparticle (UCNP) core, a middle silica shell with the first photosensitizer (PS) methylene blue (MB) encapsulated, and an outside mesoporous silica shell with the second PS rose bengal (RB) electrostatically attached to the channel walls and anticancer drug doxorubicin hydrochloride (DOX) uploaded into channel pores later. Cyclodextrine (CD) is next conjugated on the nanoparticle surface via acid-labile bond as gatekeeper to block pore openings and it can be dissociated in the acid microenvironment of cancer cells to release drug for Chemo. Upon near-infrared light irradiation, the upconverted red and green lights by UCNP core activate MB and RB simultaneously producing maximized singlet oxygen (¹O₂) for PDT to efficiently further kill the Chemo-treated cancer cells in a synergistic way. The anticancer effect of the nanoparticles was demonstrated both in vitro and in vivo. The combination of Chemo and PDT showed significantly enhanced therapeutic effect compared to single Chemo or PDT, endowing the core/shell/shell structure nanoparticle with a great potential for synergistic cancer treatments.