Nanocarrier-based drug delivery via cell-hitchhiking: Emphasizing pharmacokinetic perspective towards taming the “big-old” tumors

Nanocarriers (NCs) are widely explored in the development of anti-tumor therapeutics. NCs offer many advantages over conventional drug delivery systems (DDS) such as improved solubility/bioavailability of hydrophobic drugs; improved stability of degradation-prone drugs, provision for surface-functionalization and active targeting. Despite of such advantages, NCs showed marginal success in clinical translation. This could be due to their rapid entrapment in liver and spleen, and poor systemic half-life. Further, NCs are unable to extravasate effectively in the tumor microenvironment (TME). Thus, NCs demonstrate poor accumulation in TME, leading to sub-optimal therapeutic efficacy. The emergence of cell-based drug delivery systems benefited the field of drug delivery by offering superior biocompatibility, biostability, high systemic half-life and tumor-penetrating potential. Therefore, these systems have been developed to counter the aforementioned limitations of NCs. In this review, we discuss different cells used to hitchhike NCs to the TME and methods of cell-hitchhiked formulation preparation and characterization. The rationale and advantages of using different cells i.e. red blood cells (RBCs), monocytes/macrophages, neutrophils, T cells, platelets and mesenchymal stem cells in tumor management have been explained. We have briefly defined the potential of physiology-based pharmacokinetics evaluation for improved estimation of anticancer nanocarriers. Further, potential bottlenecks in translating cell-hitchhiked DDS to the clinic have been mentioned.