Human serum albumin-based nanomedicines for efficient treatment of cancer and rheumatoid arthritis

Nanotechnology has paved the way for the emergence of a new class of drugs based on nanoengineered particles. These “nanomedicines” are mainly designed to enhance both the specificity and the delivery of drugs in diseased tissues. Among them, human serum albumin (HSA)-based nanomedicines have been regarded as excellent drug carriers due to their low immunogenicity, good biocompatibility, long serum circulation time, and intrinsic ability to interact with transport receptors highly expressed on targeted cells. Although these properties have been sufficiently beneficial to translate some HSAbased anomedicines into clinics in cancer therapy, many formulations still suffer from poor accumulation in the tumour site and/or poor ability to efficiently eradicate cancer cells. Additionally, the exploitation of the potential therapeutic benefits of HSA-based nanomedicines in the treatment of chronic inflammatory diseases is still at the infancy. In this thesis work, we described the development of two novel HSA-based nanomedicines for the treatment of cancer and rheumatoid arthritis (RA), respectively. For the treatment of cancer, the HSA-based nanomedicines were loaded with a combination of the photosensitizer indole green (indocyanine green, ICG) and tirapazamine (TPZ). The nanomedicines triggered an anti-cancer synergistic therapy in response to a cascade of laser irradiations and led to the complete eradication of the tumor mass in a murine breast cancer model without detectable side effects. The nanomedicines can also fulfill both fluorescence and photoacoustic in vivo imaging. For the treatment of RA, the HSA-based nanomedicines were loaded with methotrexate (MTX) and showed a higher therapeutic index and lower toxicity than free MTX at half of the MTX dose in a collagen induced arthritis (CIA) mouse model. Thus, our results suggest that HSA-based nanomedicines can be developed as an efficient platform to treat not only cancer but also RA as well as other inflammation-related diseases.