A UCN@mSiO2@cross-linked lipid with high steric stability as a NIR remote controlled-release nanocarrier for photodynamic therapy

Abstract

In clinics, the application of photodynamic therapy (PDT) in deep tissue is severely constrained by the limited penetration depth of visible light that was used for activating the photosensitizer (PS). In this work, a protocol of a UCN@SiO₂@crosslinked lipid triple layer nanoparticle was developed successfully. The triple layer nanoparticle was assembled from the hydrophobic upconverting nanoparticle (UCN) core, the mesoporous silica middle shell and the cross-linked lipid out shell. The photosensitizer zinc phthalocyanine (ZnPc) loaded triple layer nanoparticle offers possibilities to solve the problem mentioned above. The UCN core works as a transducer to convert deeply penetrating near infrared light to visible light for activating ZnPc for photo dynamic therapy. The middle shell is used for loading ZnPc and the out shell can prevent the drug leaking effectively. The experiment results showed that with the help of the cross-linked lipid shell, the triple layer nanoparticle could prevent the drug leaking and particle aggregation. The ROS production test and PDT test suggested that the fluorescence emitted from the UCNs excited by NIR can effectively activate the photosensitizer ZnPc to generate cytotoxic ROS. The UCN@SiO₂@crosslinked lipid triple layer nanoparticle modified with RGD has a much better treatment effect in cancer cells. Our data suggest that the UCN@SiO₂@crosslinked lipid triple layer nanoparticle may be a useful nanoplatform for future PDT treatment in deep cancer therapy based on the upconverting mechanism.