Remodeling the Tumor Microenvironment with Emerging Nanotherapeutics

The tumor microenvironment (TME) has profound impacts on cancer progression and remodeling of the TME has emerged as a strategy to facilitate cancer therapy. Recently, great progress in TME modulation has been made, especially with the rapid developments in nanomedicine. In this review we outline the latest advances in remodeling of the TME based on nanotherapeutics. First, novel strategies developed to modulate the tumor extracellular matrix (ECM) are discussed, including disruption, mimicking, and intervening in tumor ECM fabrication. Then, emerging tumor-associated fibroblast (TAF)-based nanotherapeutics are reviewed, including disruption and targeting of TAFs. Furthermore, recent developments in tumor vessel disruption and normalization are discussed. Finally, emerging approaches in response to tumor hypoxia are presented, with special emphasis on delivering oxygen, generating oxygen, and targeting tumor hypoxia.