Encapsulating pH-Responsive Doxorubicin-Phthalocyanine Conjugates in Mesoporous Silica Nanoparticles for Combined Photodynamic Therapy and Controlled Chemotherapy.

摘要: Doxorubicin (Dox) was conjugated to a zinc(II) phthalocyanine (ZnPc) via an acid-cleavable hydrazone linker. This conjugate, having azido group, then anchored the nanochannels of alkyne-modified mesoporous silica nanoparticle (MSN) system copper(I)-catalyzed azide-alkyne cycloaddition reaction. An analogous nanosystem also prepared by immobilization hydrazine-substituted ZnPc MSN followed coupling with Dox for comparison. The release under acidic conditions studied in phosphate buffered saline 0.5% Tween 80 monitoring reduction Forster resonance energy transfer from excited after cleavage linker, and increase fluorescence released during dialysis. After internalization into human hepatocellular carcinoma HepG2 cells, these nanoparticles showed not only ZnPc, but Dox's fluorescence, which suggested that intracellular environment had triggered cleaving chemocytotoxic together singlet oxygen generated upon irradiation on encapsulated MSNs could kill cells effectively. With certain drug dose, they caused synergistic cytotoxicity as proved less than unity combination index. These thus possess dual function nanophotosensitizers photodynamic therapy nanoplatforms pH-controlled release.