“9.61x6.69” b2815 Tissue Engineering and Nanotheranostics
Multifunctional Nanomaterials for Cancer Theranostics 231
reactions are often appended,^71 which further increases the adverse
drug reactions. The use of nanocarriers such as polymers, mesoporous
silica, carbon nanotubes (CNTs) can provide both a hydrophobic and
hydrophilic environment, loading room which enhances solubility and
overcomes the side effects of the cosolvent added.^72 (2) Drug burst
release and rapid clearance. Without the loading and delivery by nano
materials, chemotherapy drugs will be immediately absorbed and dis
tributed in the major organs once they enter the body, causing damage
to the normal tissues. In addition, the drugs will be soon metabolized
and excreted, which subsequently requires repeated high dosages. By
the protection of nanomaterials, the encapsulated drugs in delivery
vehicles are more stable. Meanwhile, the behavior of slow release is
beneficial to reduce the damage caused by the rapid absorption and
distribution with traditional drug delivery routes. (3) Poor drug biodis
tribution. Due to their nonspecific nature, only limited chemothera
peutic drugs reach the tumor tissues, and the majority are distributed
to other normal tissues. By modifying the targeting ligands on the
surface of nanomaterials, the targeting drug delivery systems can signifi
cantly be taken by tumor tissues through recognizing the receptors on
the surface of the tumor cells, which reduces drugs toxicity to normal
tissues and enhances the delivery of drugs to the site of interest.
Therefore, the targeting drug delivery nanosystems have unparalleled
advantages compared with current chemotherapeutics administration
routes as well as great potential for the future.
It should be noted that not any nanocarriers can be achieved
in vivo drug delivery and cancer therapy. The physicochemical differ
ences of nanomaterials have a significant influence in the in vivo dis
tribution and cellular internalization, including their size, shape,
charge, etc.^73
Effect of size. The size of nanomaterials mainly affects the bio
distribution, kinetics of release, and cellular uptake.74–76 The mecha
nisms of uptake of nanomaterials are known as phagocytosis, diffusion,
and fluid phase endocytosis, through passive targeting, adsorptive
mechanisms, active targeting and receptormediated endocytosis,
respectively.77,78 The nanomaterials with smaller size as a foreign
objects are often not recognized by macrophages but microparticles
