Tumor heterogeneity and nanoparticle-mediated tumor targeting: the importance of delivery system personalization

After the discovery of the enhanced permeability and retention effect in 1986, it was envisioned that nanoparticle-mediated tumor-targeted delivery of chemotherapeutics would make a radical change in cancer therapy. However, after three decades of extensive research, only a few nanotherapeutics have been approved for clinical use. Although significant advantages of nanomedicines have been demonstrated in pre-clinical studies, clinical outcome was found to be variable. Advanced research has revealed that significant biochemical and structural variations exist between (and among) different tumors. These variations can considerably affect the tumor delivery and efficacy of nanomedicines. Tumor penetration is an important determining factor for positive therapeutic outcome and same nanomedicine can show diverse efficacy against different tumors depending on the extent of tumor accumulation and penetration. Recent research has started shading light on how the tumor variations can influence nanoparticle tumor delivery. These findings indicate that there is no "ideal" design of nanoparticles for exhibiting equally high efficacy against a broad spectrum of tumors. For achieving maximum benefit of the nanotherapeutics, it is necessary to analyze the tumor microenvironment for understanding the biological and structural characteristics of the tumor. Designing of the nanomedicine should be done according to the tumor characteristics. In this comprehensive review, we have first given a brief overview of the design characteristics of nanomedicine which impact their tumor delivery. Then we discussed about the variability in the tumor architecture and how it influences nanomedicine delivery. Finally, we have discussed the possibility of delivery system personalization based on the tumor characteristics.