Oxygen and pH responsive theragnostic liposome for early-stage diagnosis and photothermal therapy of solid tumour

The development of cancer treatment is of great importance especially in the early stage. In this work, we synthesized pH-sensitive amphiphilic ruthenium complex containing two alkyl chains and two PEG chains which was utilized as oxygen sensitive fluorescent probe for co-assembly with lipids to harvest a liposomal delivery system (RuPC) for the encapsulation of a photothermal agent indocyanine green (ICG). The resultant ICG encapsulated liposome (RuPC@ICG) enabled to deliver ICG into cells via membrane fusion pathway by which the ruthenium complex was localized in the cell membrane for better detecting the extracellular oxygen concentration. Such characteristic endowed the ratiometric imaging feature to distinguish tumour location from normal tissues at just 3 days after cancer cells were implanted by monitoring the hypoxia condition and tracing the metabolism. Moreover, the pH sensitivity of the liposomes favoured the cell uptake, and improved the anti-tumour efficiency of the formulation in vivo under NIR irradiation. Should liposomal systems have less safety issue, our work not only provided a facile way for the construction of theragnostics by combining phototherapy with photoluminescent imaging, but hopefully paving the way for the clinical translation from bench to bedside.