Engineering Tumor-Targeting Nanoparticles as Vehicles for Precision Nanomedicine

As a nascent and emerging field that holds great potential for precision oncology, nanotechnology has been envisioned to improve drug delivery and imaging capabilities through precise and efficient tumor targeting, safely sparing healthy normal tissue. In the clinic, nanoparticle formulations such as the first-generation Abraxane® in breast cancer, Doxil® for sarcoma, and Onivyde® for metastatic pancreatic cancer, have shown advancement in drug delivery while improving safety profiles. However, effective accumulation of nanoparticles at the tumor site is sub-optimal due to biological barriers that must be overcome. Nanoparticle delivery and retention can be altered through systematic design considerations in order to enhance passive accumulation or active targeting to the tumor site. In tumor niches where passive targeting is possible, modifications in the size and charge of nanoparticles play a role in their tissue accumulation. For niches in which active targeting is required, precision oncology research has identified targetable biomarkers, with which nanoparticle design can be altered through bioconjugation using antibodies, peptides, or small molecule agonists and antagonists. This review is structured to provide a better understanding of nanoparticle engineering design principles with emphasis on overcoming tumor-specific biological barriers.