An albumin nanocomplex-based endosomal pH-activatable on/off probe system

Albumin has gained considerable interest as a material for fabricating nanoparticulate systems due to its biomedical advantages, such as biocompatibility and chemical functionality. Here, we report a new pH-sensitive albumin nanocomplex prototype with a zinc-imidazole coordination bond. Albumin was conjugated with 1-(3-aminopropyl)imidazole and mPEG_{10 kDa}-NHS, and the resulting albumin conjugate (PBI) was then modified with either Cy5.5 or BHQ-3. The newly formed albumin nanocomplex (C/BQ-PBI Zn NCs: ~116 nm) system was facilely self-assembled around pH 7.4 in the presence of Zn²⁺, but it quickly disassembled in an acidic environment (~pH 5.0). Based on this pH-sensitivity, C/BQ-PBI Zn NCs emitted strong near-infrared fluorescence and released Zn²⁺, turning "off" at pH ~7.4 (e.g., plasma) and "on" at pH ~5.0 (e.g., endo/lysosomes in tumor cells) on account of fluorescence resonance energy transfer. C/BQ-PBI Zn NCs displayed significant cytotoxicity due to an increase in cellular Zn²⁺ in response to endosomal pH (~5.0) in breast cancer MCF-7 cells and lung adenocarcinoma A549 cells. Particularly, confocal laser scanning microscopic images showed a strong fluorescence signal caused by the disassembly of C/BQ-PBI Zn NCs in the endosomal region of MCF-7 cells. Based on these results, we believe that this albumin nanocomplex is an attractive biocompatible tumor targeting probe carrier for the theranostic purpose.