Tissue Engineering And Nanotheranostics

b2815 Tissue Engineering and Nanotheranostics “9.61x6.69”

242 Tissue Engineering and Nanotheranostics

carrier for siRNA delivery and is currently in clinical testing. Another

drug in phase I/II trials is annamycin to treat acute lymphocytic

leukemia.

4. Targeting Strategy

4.1. Passive Targeting

Passive targeting is the penetration of nanocarriers through leaky

tumor capillary fenestrations into the tumor interstitium and cells by

convection or passive diffusion.217–219 Due to the vascular structure of

tumors, selective accumulation of nanocarriers and drugs can be easily

carried out by the EPR effect that is now becoming the gold standard

in cancer­targeting drug designing. The EPR effect is applicable for

almost all solid tumors, and can be observed in almost all human

cancers with the exception of hypovascular tumors.220–222 For the

nanocarriers to evade immune surveillance and circulate for a longer

period, the EPR effect should be optimal. A large number of studies

have shown that higher local concentrations of drug­loaded nanocar­

riers can be achieved at the tumor site, with ca. 50­fold higher con­

centration than that in normal tissue within several days.^223 In order

to achieve the desired passive targeting effect by the EPR effect, more

attention should be paid to at least three properties of nanocarriers.

Firstly, the size of the nanocarrier must be strictly controlled. The

ideal nanocarrier size is somewhere between 10 and 100 nm.224–226

The nanocarriers of sizes smaller than 10 nm are easily filtrated by the

kidneys, and with size larger than 100 nm, are specifically captured by

the liver.227,228 Secondly, the charge of the nanocarrier is neutral or

anionic for efficient avoidance of the renal elimination.81,229 Last but

not least, the nanocarrier should be camouflaged to hide from the

reticulo­endothelial system, which destroys all exogenous foreign

bodies through opsonization followed by phagocytosis. However,

there are shortcomings to solely relying on the EPR effect for passive

targeting. The degree of tumor vascularization and angiogenesis

affect the effect of the passive targeting. The nanocarrier should be

designed according to tumor types and anatomical sites. On the other