Design and Development of Theranostic Nanomedicines - Nanotechnology for Biomedical Imaging and Diagnostics - page 427

side effects, pTT is active within limited area and thus can reduce normal tissue
damage. For instance, it has been demonstrated that peg-coated gold nanocages
increased the tumor surface temperature to 54°C within 2 min under illumination of
nir light [42].
similar to many other nanomaterials, gnps can be delivered to the tumor in a
passive fashion, where circulating gnps can penetrate the leaky tumor vasculature
and accumulate in the tumor. For example, after being injected intravenously into
tumor-bearing mice, nir pegylated nanoshells were shown to be heterogeneously
located in tumors, mostly in the tumor cortex and absent from the tumor core [43].
For targeted delivery of the nanomaterial, targeting molecules can be conveniently
attached to the surface of gnps, typically through thiol-mediated conjugation. some
examples of targeting molecules that have been attached to gnps include antibodies
[44, 45], antibody fragments [46], receptor ligands [47, 48], and peptides [49, 50].
The most common method to synthesize gnps is chemical reduction of gold salt
to metallic gold with a capping ligand, which is typically a thiol [51]. one example
is Brust-schiffrin reaction, in which sodium borohydride is used to reduce gold
chloride to gold with dodecanethiol as the capping ligand [52]. The gnps produced
have small sizes (1-3 nm) and are highly stable. however, ligand exchange or addi-
tional coating is needed for biological applications as these gnps are not soluble in
aqueous solutions. The most widely used coating molecule is peg, which increases
hydrophilicity and lengthens blood circulation time [53]. as previously mentioned,
the thiol components involved in gnps synthesis can be readily used to conjugate
with other functional molecules, such as targeting, signaling, and therapeutic agents.
With stability, strong spr, and ease of surface modification, gnps have been
exploited as an attractive platform for theranostic applications. For example, peg-
coated gnps were used to treat human xenograft tumor in mice through pTT, and the
therapy was guided by CT [54]. The peg coating is important for gnps to traverse
the systemic circulation, deter protein binding and res clearance, permeate through
transendothelial pores in tumor blood vessels, and be retained in the tumor intersti-
tium [54]. as a result, the circulation time of the pegylated gnps was as long as
17 h, thus allowing for cancer therapy through passive targeting. Compared to the
controls, the pegylated gnps showed much higher potency.
The therapeutic efficacy of gnps can be further improved by specific delivery and
combining pTT and anticancer drug. in a study reported by You et al ., DoX and a
targeting molecule for ephB4 (a receptor overexpressed by multiple tumors and
angiogenic blood vessels) were loaded to gold hollow nanospheres [55]. The resulting
multifunctional gnp, T-DoX@hauns, was evaluated in three mouse tumor models.
in addition, 111 in was used to label the theranostic gnp to image the biodistribution
and tumor uptake using speCT. Treatment with T-DoX@hauns followed by nir
irradiation to release DoX resulted in significantly decreased tumor growth when
compared with treatments with nontargeted DoX@hauns or hauns without DoX.
in contrary to the group treated with DoX only, none of the treatment groups experi-
enced a loss in body weight, suggesting lower side effects. These encouraging results
indicate that combinatory therapy with chemo and pTT using targeted gnps as the
carrier is a promising approach for cancer therapy.