Nano- and micro-delivery platforms for protein-based multimodal and synergetic breast cancer therapy

Protein therapeutics have opened a new world for cancer therapy due to its specificity on therapeutic targets. Still, some types of protein therapeutics, including pro-apoptosis proteins and enzymes, rarely enter the oncology market because of their intrinsic challenges, such as susceptibility, instability, poor intracellular delivery, limited tumor accumulation, systematic toxicity, etc. This thesis aims to solve such challenges and amplify the therapeutic potency of protein therapeutics based on micro- and nano-particle platforms. In Chapter 1, we introduced the types of protein therapeutics and their delivery platforms, as well as protein combinational strategies based on delivery platforms. In Chapter 2, we introduced the Fenton reaction, a ROS generator applied later in Chapters 4 and 5. In Chapter 3, we fabricated a liposomal nano-platform for intracellular delivery of Cyt C, one of the pro-apoptosis proteins, then enhanced Cyt C therapeutic effect by lonidamine combination in breast cancer model. In Chapters 4 and 5, we fabricated two kinds of injectable hydrogel microspheres for lactate oxidase (Chapter 4) and glucose oxidase (Chapter 5)-based local breast cancer treatment. The therapeutic effects of two enzymes are promoted by combination with anti-metabolic and photothermal therapy, respectively. In summary, we provide new insights to overcome protein delivery challenges and improve protein therapeutic effects by combinational strategies.