Pandia: Gold Nanorods and Their Applications in Cancer Therapy and In Vivo Imaging in Companion Animals and Their Potential Application to Humans - Nanotechnology for Biomedical Imaging and Diagnostics - page 355

the NRs undergoing sonic cavitation that will further disrupt tumor vascularity.
histopathologic evidence of necrosis was present in two per six dogs and one dog
had evidence of tumor regression.
NRs can potentially be loaded with chemotherapeutic agents (doxorubicin, Taxol)
using a heat-sensitive or ph-sensitive linker. In such construct, chemotherapeutic is
released locally following the application of the NIR diode laser.

12.4 PoTenTial aPPlicaTions in humans

To establish a basis of safety for the IV injection of PeG-coated AuNRs for in vivo
photothermal cancer therapy in humans, we have analyzed (i) historical toxicity
analysis of gold nanoparticles used in treating arthritis, (ii) current uses of polyeth-
ylene glycol (PeG), (iii) survey of existing published literature and credible web
sources regarding toxicology studies, (iv) current toxicology results in healthy dogs,
(v) future human toxicology study plans, and (vi) potential for AuNR use as improved
drug delivery tools.
We found in the literature that over 40 years of historical use in the treatment of
rheumatoid arthritis have shown no known cytotoxic reactions in amounts much
greater and in longer duration than what is proposed for the current study. PeG is
used widely in improving the efficacy of drugs for in vivo use and in many other
applications. Mice studies have shown no known cytotoxicity and 35% clearance
from major organs after 120 days. Our current toxicity studies in healthy dogs have
shown neither short-term nor long-term toxic reactions. Further, published literature
shows canines are currently being used as models for human cancer research [55].

12.4.1 historical Toxicity analysis of old nanoparticles
used in Treating arthritis

According to huerta et al . [56], gold compounds and penicillamine are older drugs
that are used less frequently in rheumatic diseases but can be considered for patients
who cannot tolerate other drugs. Gold sodium thiomalate and gold thioglucose (auro-
thioglucose) are injectable (e.g., intramuscularly (IM)); a test dose of 10 mg for the
first week is followed by a 25 mg dose 1 week later. All subsequent IM doses of
25-50 mg are given weekly until a cumulative dose of 1 g is achieved and a therapeutic
response or toxicity occurs. If a therapeutic response occurs, maintenance doses of
25-50 mg are continued weekly, then every 2 weeks, then every 3 weeks, and then
monthly. Monthly therapy should be continued indefinitely to prevent a recurrence.
Our efforts in canines show that we need a one-time single injection of between
0.2 and 2 g in an adult male human. This compares to gold salts, which according to
the Merck Manual of Geriatrics for treatment of rheumatic diseases recommends
weekly injections to an accumulation of 2 g with 50 mg monthly injections, thereafter
indefinitely.
According to Lawrence [57], gold salts have been used in the treatment of arthritis
since the favorable report of Forestier in 1929. Oily suspensions were introduced