Personalized Cancer Nanomedicine: Overcoming Biological Barriers for Intracellular Delivery of Biopharmaceuticals

Abstract The success of personalized medicine in oncology relies on using highly effective and precise therapeutic modalities such as small interfering RNA (siRNA) and monoclonal antibodies (mAbs). Unfortunately, the clinical exploitation of these biological drugs has encountered obstacles in overcoming intricate biological barriers. Drug delivery technologies represent a plausible strategy to overcome such barriers, ultimately facilitating the access to intracellular domains. Here, an overview of the current landscape on how nanotechnology has dealt with protein corona phenomena as a first and determinant biological barrier is presented. This continues with the analysis of strategies facilitating access to the tumor, along with conceivable methods for enhanced tumor penetration. As a final step, the cellular barriers that nanocarriers must confront in order for their biological cargo to reach their target are deeply analyzed. This review concludes with a critical analysis and future perspectives of the translational advances in personalized oncological nanomedicine.