Tumor Microenvironment-Enabled Nanotherapy

Cancer is now one of the world's leading threats to human health. With the development of oncology in both biology and biomedicine, it has been demonstrated that abnormal physiochemical conditions and dysregulated biosynthetic intermediates in tumor microenvironment (TME) play a pivotal role in enabling tumor cells to defend or evade the damage by traditional clinical tumor therapeutics including surgery, chemotherapy, radiotherapy, etc. The fast advances of TME-enabled theranostic nanomedicine have offered promising perspectives, strategies, and approaches for combating cancer based on the novel concept of TME-enabled nanotherapy. In this comprehensive review, the origins of TME (e.g., enhanced permeability and retention effect, overexpressed biosynthetic intermediates, mild acidic nature, redox potentials, hypoxia) are initially introduced and discussed, followed by detailed discussion and overview on the state-of-the-art progresses in TME-enabled antitumor nanotherapies (e.g., chemo/chemodynamic therapy, photodynamic therapy, radiotherapy). Finally, the obstacles and challenges of future development on TME-enabled nanotherapies for further clinical translation are outlooked.