In specified organs, penetrate through cell membranes, enter

In the current study, we used a
multifunctional nanoparticle as PLGA-coated gold magnetic to enhance
therapeutic index in the presence of radiation and hyperthermia. For this
purpose, we investigated the cytotoxic effects induced by nanoparticles in
combination with megavoltage electron radiation (6MeV) and water bath
hyperthermia (43°C) on DU145 prostate cancer cell line in monolayer culture.
The Spheres are more radioresistant than parental cells, thus sphere formation
is especially useful to enrich the cancer stem cells subpopulations and also to
determine the response to various therapeutic modality (19). In order to assess the combined
effect of hyperthermia and ionizing radiation with nanoparticles on the
self-renewing and differentiating potential of the DU145 prostate cells, we used sphere formation assay and
colony formation assay, respectively (20). 

Nanoparticles, particularly noble
metal and magnetic nanoparticles, can be useful in enhancing the efficacy of
hyperthermia and radiotherapy due to their unique chemical and physical
properties (11, 12). Nanoparticles larger than 300 nm
are potentially removed by macrophages, smaller ones can circulate within blood
vessels, target specified organs, penetrate through cell membranes, enter the
mitochondria, and trigger apoptotic responses (13), but when smaller than 30 nm, they
leave it again by passive diffusion (14). Gold nanoparticles (GNPs) are
suitable as radiosensitizers because of GNPs irradiated with kilovolt­age
photons due to their high atomic number (Z=79) which results in better mass
energy absorption compared to soft tissue (15) furthermore the higher atomic
number increases probability of photoelectric effect, as the density of
electrons in the molecule (14) and GNPs exposed with clinical MV
photons to produce a poor enhancement effect because of the Compton scattering
per unit mass for gold nanoparticle and soft tissue. However, a research on the
secondary electrons showed a dose increase in the vicinity of the gold
nanoparticles exposed to MeV photons due to the cascading Auger electrons following
a single ionization incident (16). Moreover, Magnetic nanoparticles
such as iron oxide can also be used for combined hyperthermia and radiation (17). In recent times magnetic iron
oxide nanoparticles have been in development for many applications such as cancer
therapy and when a radiation beam interacts with metallic nanoparticles, free
radicals are produced that can directly strike DNA molecule and indirectly
induce apoptotic cell death (13). In comparison with GNPs, iron
oxide nano­particles have lower photon absorption (absorption enhance­ment
factor of about 1.2) but nevertheless, they can be effective as a
radiosensitizer and thermal sensitizer (11).

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Hyperthermia is nowadays a suitable
physical method in cancer therapy that enhances the cytotoxic effects of
radiotherapy (thermal radiosensitization). According to the National Cancer
Institute, hyperthermia kills cancer cells by increasing temperature to the
therapeutic range, 42-45°C at a certain time (8). Various studies (in vitro, in vivo
animal, and clinical trials) have proved that hyperthermia can serve as a
powerful tool in the treatment of prostate cancer but the use of hyperthermia
in combination with radiotherapy enhances therapeutic index due to their
different mechanisms of interaction with cells and tissue (9). The most important reason of the
success of hyperthermia in improvement radiosensitization of CSCs lies in
preventing the damaged DNA from repairing itself and decreasing the survival
rate of these cells (10).

Prostate cancer
(Pca) is usually a very slow progressing disease in males. PCa is the second leading cause of
cancer death, particularly in the developed countries (1). Treatment of
PCa often depends on the stage of cancer and the age
of the patient. Some of the most common therapies for prostate cancer include
surgery, radiotherapy, chemotherapy, thermal therapy, hormone therapy or some
combination (2). Of these, ionizing radiation is often used to
treat localized prostate carcinoma (3). One of the major challenges in
radiation therapy is to deliver a maximum dose of a radiation beam to the solid
tumor and preserve the normal tissues around a tumor. Although increasing
radiation dose can increase cell death, acute and late side effects often limit
its use in patients thus, there is a limitation in increasing radiation dose.
Hence in clinical radiotherapy, even though radiation represents the maximal
effect of treatment but cannot kill all the cells within a prostate tumor (4). Actually intrinsic radioresistance
of cancer stem cells (CSCs) is the reason of the failure of radiotherapy to
eliminate all the cells able to regrow the tumor, which will lead to relapse
due to cancer cell repopulation (5). To overcome radioresistance CSCs,
combination therapies and radiosensitizers are appropriate solutions (6, 7).


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