Advances in Nanoarchitectural Designs for Anticancer Drug Delivery to Deep Tumors

Extensive progress in the design of drug delivery systems based on advanced materials offers new and exciting opportunities in the fight against cancer. However, multiple challenges remain to be addressed before this approach can find a widespread application in clinics. Here, we provide a comprehensive overview of various innovative nanoparticle design strategies, including ultrasmall-size, size-shrinkable and multi-stage degradable nanoparticles, anisotropic particles with irregular dimensions, electrostatically-driven charge-reversal nanoparticles, and bioinspired carriers. We also discuss in detail the process of infiltration and various challenges faced by the nanoparticle-based delivery systems and highlight the roles of various factors (size, shape, chemistry, and surface charge) affecting tumor penetration by nanoparticles. In addition, the crucial roles of tumor size and metastatic stage in influencing the therapeutic efficacy of nanoparticles are highlighted. Finally, we discuss emerging highly advanced intelligent drug delivery platforms based on nanorobotics/nanomotors and immunotherapeutic activation.