Biomedical Engineering Reference
In-Depth Information
tumor blood vessels, the carrier may fall into the pores in the blood vessel wall
and extravasate into the tumor tissue (EPR effect) (Figure 3.1A).
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Next, it
may further penetrate through the tumor tissue, which is nontrivial because of
the high cell density and high interstitial fluid pressure (IFP) (Figure 3.1B).
7
Upon sticking to the surrounding cancer-cell membrane (Figure 3.1C), the
carrier is expected to enter the cells via one or several possible pathways, and
finally traverse the crowded intracellular structures and viscous cytosol to the
targeted subcellular sites and release the carried drug cargo.
Thus, to achieve efficient drug delivery from the i.v. injection site to the target in
the tumor cells, the nanocarrier must simultaneously meet two pairs of challenges
(Figure 3.1): (a) the nanocarrier must retain the drug very tightly, ideally without
any release, during the transport in the blood compartments and the tumor tissue,
but must be able to efficiently release the drug once reaching the intracellular
target to exert its pharmaceutical action; (b) the nanocarrier must be ''slippery'' or
''stealthy'' while in the blood compartments and in the tumor tissue until it reaches
the targeted tumor cells. The stealth in the blood compartments enables it to
effectively evade the reticuloendothelial system (RES) screening, particularly the
capture by liver and spleen for a long blood circulation time. As the blood
circulation time of the nanocarrier increases, so does its opportunity to pass the
hyperpermeable tumor blood vessel and extravasation into the tumor tissue. After
extravasating into the tumor, the nanocarrier must remain ''stealthy'' to penetrate
deep into the center region to deliver the drug. This region lacks vascular perfusion
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Figure 3.1
Cancer drug delivery process: (A) transport in the circulation, (B) transport
through the tumor tissue, and (C) transport in the tumor cell. The nanocarrier
must meet two pairs of challenges — For the drug: the nanocarrier must
retain the drug very tightly during the transport in the blood compartments
and the tumor tissue but efficiently release the drug once reaching the
intracellular target; For the surface: the nanocarrier must be ''very stealthy''
during in the blood compartments for a long blood circulation time and
remain ''stealthy'' in penetrating the tumor tissues but must become ''sticky''
or ''cell binding'' once interacting with tumor cells for efficient cellular uptake.
