One-pot synthesis of theranostic nanocapsules with lanthanide doped nanoparticles

Abstract

We report a one-pot synthesis strategy for a new theranostic nanoplatform by simultaneously encapsulating Er³⁺, Yb³⁺ doped NaGdF₄ upconverting nanoparticles (UCNPs) and photosensitizer zinc phthalocyanine (ZnPc) into polymeric micelle/silica nanocapsules. This approach consists of interfacial templating condensation, using triblock copolymers, namely (ethylene oxide)₁₀₆(propylene oxide)₇₀(ethylene oxide)₁₀₆ (PEO-PPO-PEO) as the templating and protecting agent. The encapsulation follows a straightforward microemulsion mechanism in an aqueous environment at a near-neutral pH. To prevent the interaction between the hydrophobic oleic acid (OA) ligands of UCNPs and the silanol groups of hydrated tetramethoxysilane (TMOS), we adjusted the addition sequence of TMOS. It allowed us first to encapsulate UCNPs in PEO-PPO-PEO micelles, and then grow the silica shell within the micellar PPO core and PEO corona interface. The silica shell is incorporated for its chemical and mechanical stability, while the PEO corona gives additional steric balance to the nanocapsule. Using this strategy we successfully co-encapsulated UCNPs and ZnPc in one-pot, and minimized the distance between the two payloads to facilitate the energy transfer from UCNPs to ZnPc. The integrated nanocapsule has an average hydrodynamic size of 85 nm with a low polydispersity index of 0.1, and demonstrates excellent colloidal stability, biocompatibility, enhanced negative contrast for T₂-weighted imaging and photodynamic therapy. The latter is obtained through indirect excitation of co-encapsulated ZnPc by UCNPs, resulting in singlet oxygen generation and in vitro eradication of BT474 breast cancer cells. Overall, the presented one-pot approach shines light on the co-encapsulation of OA-capped inorganic UCNPs with hydrophobic photosensitizers, constituting an important step forward in the surface engineering of UCNPs, as well as upconversion based photodynamic therapy systems.