One-Pot Synthesis of Theranostic Nanocapsules with Lanthanide Doped Nanoparticles

In this work, we have established a one-pot synthesis strategy to develop 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 consisted of interfacial templating condensation, using triblock copolymers, ethylene oxide)106(propylene oxide)70(ethylene oxide)106 (PEO-PPO-PEO), as the templating and protecting agent. The encapsulation followed a straightforward microemulsion mechanism in an aqueous environment of a near neutral pH. The surface hydrophobic nature of UCNPs is crucial for the success of encapsulation. To prevent the interaction between the hydrophobic OA ligands of UCNPs and the silanol groups of hydrated tetramethoxysilane (TMOS), we modified the previous procedure by tuning the addition sequence of TMOS. It allowed 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 confers additional steric stability to the nanocapsule. Using the modified 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, as compared to conventional PS loading in the mesoporous silica coating. 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, as well as 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 shined 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 delivery systems.