Journal of Infertility and Reproductive Biology, 2017, Volume 5, Issue 2, Pages: 5-11  
The Role of Nanotechnology-Based Photodynamic  
Therapy in the Treatment of Ovarian Cancer  
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Mitra Taghipour , Marzieh Khodadadi , Hamid Reza Ghaderi Jafarbeigloo , Faezeh Jadidi *,  
Mahmoud Mehdinejad5*  
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Department of Biotechnology, Faculty of Agriculture and Natural Resourses, Imam Khomeini International University, Qazvin, Iran  
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Department of Chemistry, Faculty of Chemistry, Payame Noor University (PNU), P.O. Box, 19395-3697, Tehran, Iran  
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Department of Basic Science, Payame Noor University, Iran  
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Student Resesrch committee, Zarand School of Nursing, Kerman University of Medical Sciences, Kerman, Iran  
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Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shahroud University of Medical Sciences,  
Shahroud, Iran  
Received: 06/3/2017  
Accepted: 13/07/2017  
Published: 20/09/2017  
Abstract  
Ovarian cancer is one of the most dangerous and deadly cancers in women. This cancer progresses very quickly and metastasizes to  
the peritoneal cavity and pelvis. It is called silent death because 75% of patients who refer to hospitals are diagnosed at advanced stages  
of the disease. Transvaginal ultrasonography, Cancer antigen (CA125, Doppler imaging, Human kallikrein 10 (hK10), lysophosphatidic  
acid (LPA), computerized tomography scans, cytology and / or biopsy are used to diagnose ovarian cancer. Surgery and chemotherapy  
are also among common treatments used for the treatment of ovarian cancer. However, these traditional therapies have a variety of side  
effects, including nausea, vomiting, peripheral neuropathy, neurotoxicity. Nanotechnology with its unique features can overcome these  
limitations and problems. Nanoparticles can use modern therapies, such as nanotechnology-based photodynamic therapy,  
nanotechnology-based gene therapy, nanotechnology-based radiotherapy and radiofrequency therapy, and nanotechnology-based cancer  
theranostic that can helps in the treatment of cancer. Nanotechnology-based photodynamic therapy is considered one of the most  
effective, safe, and novel methods in cancer treatment. The use of nanoparticles as photosensitizers can overcome many of the limitations  
of traditional therapies. Nanoparticles can be targeted to specific sites, controllable, in some cases, used in a way to produce ROS. The  
use of nanotechnology can attenuate toxicity in target sites and greatly reduce injuries to normal cells.  
Keywords: Ovarian cancer; Nanotechnology; Photodynamic therapy, Nanoparticles, Photosensitizers  
between this cancer and other types of cancer is that unlike  
1
Introduction  
other types of cancer, caused by vascular dissemination,  
ovarian cancer rarely spreads through the angiogenesis process.  
In addition, it may involve pelvic and / or para-aortic lymph  
nodes. Patients with ovarian cancer have locally advanced  
disease in the pelvis, with contiguous extension to or  
encasement of the reproductive organs (uterus, fallopian tube,  
tube, ovaries) and the sigmoid colon (7, 9). Another type of  
tissue change occurring during ovarian cancer is the  
transformation of the omentum. During the disease, the  
omentum, a soft 20 × 15× 2-cm fat pad which covers the  
abdominal cavity and bowel, transforms and this causes  
obstruction of the stomach and the small and large bowel and  
cause severe pain to the patient (10).  
Ovarian cancer is the most common cause of mortality in  
adult women (1). Numerous studies have shown that ovarian  
cancer takes more victims than breast cancer. According to a  
study conducted by the American Cancer Society, the mortality  
rate from ovarian cancer was about 69%, while such a rate was  
about 19% fir breast cancer. Some genetic and epigenetic  
changes may occur in the body to transform a normal ovarian  
cell to a cancer cell. Some researchers believe that ovarian  
cancer is the result of a mutation in the gene on chromosome  
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7q, known as BRCA1. It is estimated that mutations in this  
gene may increase the risk of ovarian cancer by 30% in  
individuals who are over 60 years old. The origin of ovarian  
cancer may be the surfaces of the ovary, the fallopian tube, or  
the mesothelium-lined peritoneal cavity. Ovarian cancer  
mainly affects postmenopausal women and is a deadly cancer.  
The cure rate for this cancer is 30%. This may be due to the fact  
that most patients only refer to medical centers when the  
disease progresses to advanced stages with extensive metastatic  
lesions in the peritoneal cavity (2-5).  
In general, ovarian cancer accounts for 4% of all cases of  
cancer in women. In addition, gynecologic malignancies are the  
leading cause of death in females. Ovarian cancer is mostly  
asymptomatic at the early stages, indicating why most of  
patients are diagnosed at advanced stages of the disease when  
hospitalized in medical centers (6). Ovarian cancer is ranked as  
the second gynecological cancer in terms of the incidence  
among women (7, 8). Cancer cells grow rapidly in ovarian  
cancer, which is a very aggressive cancer that quickly  
metastasizes to other tissues and organs. One major difference  
2 Risk factors  
Some risk factors include: (a) several lines of evidence  
suggest that certain drugs and chemicals may increase  
gonadotropins by increasing estrogen degradation in the liver  
or directly stimulating their production by the pituitary gland.  
Pelvic irradiation, exposure of follicles to chemicals or toxic  
metabolites, or ovarian infections such as mumps are other risk  
factors of the disease development (11). (b) The long-term use  
of estrogen-only replacement therapy (particularly for 10 or  
more years) (12). (c) Women with susceptibility genes such as  
BRCAl (13-18). (d) Women who have had first-degree  
relatives with ovarian cancer (19-22). (e) In general, the  
incidence of ovarian cancer is increased with age. According to  
some studies, the incidence is higher in individuals who have  
over 60 years old. It is also very rare to occur before 40 years  
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Journal of Infertility and Reproductive Biology, 2017, Volume 5, Issue 2, Pages: 5-11  
old (23). (f) Some findings suggest the significance of  
4.1 Surgical treatment  
geographic and ethnic variations in the incidence of ovarian  
cancer. Studies showed that Caucasian women in industrialized  
countries such as the North America and Europe have a higher  
incidence of ovarian cancer than others (24). (g) Some studies  
have reported a dietary effect on the development of ovarian  
cancer. These studies have shown that Western diet, which is  
high in meats and low in vegetables may have a role in the  
incidence of ovarian cancer. Studies have also shown that  
whole-grain food, low-fat milk, calcium or lactose, vegetable,  
significantly reduced the risk of ovarian cancer (25). (h)  
Smoking and tobacco are also linked to ovarian cancer and  
increase the risk of cancer (26, 27). (i) Exposure to talc or  
asbestos has been demonstrated that cause or make individuals  
probe to develop ovarian cancer. These substances cause  
chronic inflammation in the ovarian epithelium. Inflammation  
is capable of producing oxidants that can cause direct damage  
to DNA and lead to increased proliferation of cancer cells,  
enhancing the risk of mutagenesis (28).  
The surgical procedure is the commonest invasive  
therapeutic strategy used for patients with ovarian cancer. This  
surgery includes: total hysterectomy, bilateral salpingo-  
oophorectomy, omentectomy and peritoneal cytology. These  
procedures are performed by trained gynecological specialists  
or oncologists. If the surgery process accomplished, it brings  
the best chance for the overall survival of patients.  
Laparotomy is a surgical procedure involving a large incision  
through the abdominal wall to gain access into the abdominal  
cavity. It seems that the laparoscopic removal of ovarian cysts  
is best strategy only in patients with benign cysts (41-49). The  
main purpose of cytoreductive surgery is to remove the entire  
tumor, which may have metastasized to the pelvic and  
abdominal cavities, i.e., “optimum cytoreduction,” in order to  
increase the efficacy of additional adjuvant therapy (40). In  
fact, surgery can reduce the number of tumor cells and  
subsequently the size of tumors (50).  
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.2 Chemotherapy  
Several studies show that women who have not successful  
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Diagnosis  
surgery exhibit poor prognosis in which the 5-year survival rate  
is about 0-5%. Therefore, due to the low efficacy of surgery  
alone, chemotherapy can be combined with conventional  
therapies. Chemotherapy is usually prescribed following the  
surgical procedures. Chemotherapy prevents the disease  
progress and improve the overall survival of patients with  
cancer (51-54). Chemotherapeutic agents are intravenously  
administered to patients with ovarian cancer and prescribed in  
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.1 Screening  
If ovarian cancer is diagnosed at the early stages of the  
disease, the chance of recovery is increased. Nowadays,  
ultrasound, which is a non-invasive procedure, is used for  
screening the human body (29-32).  
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.2 Transvaginal ultrasonography  
This imaging method measures the ovarian size and  
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-8 sessions. Ovarian tumors tend to be chemo-sensitive and  
confine themselves to the surface of the peritoneal cavity.  
These features have made them suitable target for  
estimates the internal ovarian structure, volume, septum  
thickness and papillary formation (33).  
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intraperitoneal (IP) chemotherapy. A group of studies have  
shown that intraperitoneal chemotherapy improves overall  
survival of patients with cancer (55). The most common drug  
used for the treatment of ovarian cancer is platinum (56).  
Nowadays, combination chemotherapy is used as a current  
regimen for the treatment of advanced ovarian cancer. Various  
chemotherapeutic agents, such as paclitaxel, topotecan,  
gemcitabine, oral etoposide, olaparib, cyclophosphamide,  
chlorambucil, melphalan, thiotepa, treosulfan, and  
encapsulated doxorubicin are prescribed in combination with  
carboplatin or cisplatin (39, 40, 57, 58)  
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.3 Doppler imaging  
This imaging method is a complementary method for  
improving the sensitivity of transvaginal ultrasound assessment  
and evaluation of angiogenesis in ovarian tumors (34, 35).  
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.4 Cancer antigen (CA125)  
This cancer antigen (CA125) is overexpressed in nearly  
2% of women with ovarian cancer compared with healthy  
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women (36).  
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.5 Lysophosphatidic acid (LPA)  
In this examination, the serum concentration of LPA is  
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.3 Some side effects of common treatments for ovarian  
cancer  
Many patients with ovarian cancer experience recurrence,  
measured and it has been shown that more than 90% of female  
patients with ovarian cancer exhibit increased levels of this  
molecule in their serum samples (37).  
despite responding well to primary chemotherapy. Whether a  
patient undergoes second or third course of chemotherapy  
mainly depends on the emergence of side effects of drugs used.  
The most common side effect reported in patients with ovarian  
cancer is chemotherapy-induced nausea and vomiting (CINV)  
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.6 Human kallikrein 10 (hK10)  
This enzyme is a secreted serine protease highly expressed  
in ovarian tissues and considered a novel biomarker for ovarian  
cancer. The serum level of hK10 is a strong and independent  
prognostic marker for ovarian cancer (38).  
(59). In addition, chemotherapy may cause neurotoxicity in the  
peripheral and central nervous system, resulting in cognitive  
deficits, encephalopathy, dementia, or even coma the adverse  
effects may limit the dosage and usage of chemotherapeutic  
agents. Bone marrow toxicity is another well-known adverse  
effects in response to chemotherapy; however, this problem  
could be partially attenuated by the administration of growth  
factors or bone marrow transplantation (60). Also, some drugs  
used for the treatment of ovarian cancer, such as a combination  
of doxorubicin hydrochloride and cisplatin, may increase the  
risk of leukemia when used in relatively high doses (39).  
Generally, an increase in the survival of patients is the major  
goal of chemotherapy, a decrease in clinical symptoms and  
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Conventional treatments  
In general, conventional treatments are routinely applied for  
patients with ovarian cancer depending on the stage of the  
disease. The first line therapy is surgery followed by  
chemotherapy and in some cases radiotherapy. In the case of  
initial responses, secondary therapy might be needed to  
complete the treatment course (39, 40).  
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Journal of Infertility and Reproductive Biology, 2017, Volume 5, Issue 2, Pages: 5-11  
preservation of the quality of life are also critical issues that  
should be taken into account. Reports indicated that  
Nanotechnology has opened new therapeutic windows for  
cancer treatment. Some of these new approaches include  
chemotherapy can cause nausea, vomiting, hair loss, cognitive  
dysfunction, fatigue, changes in sexual desire, and a reduction  
in the quality of life (61).  
nanotechnology-based  
photodynamic  
therapy,  
nanotechnology-based gene therapy, nanotechnology-based  
radiotherapy and radiofrequency therapy, nanotechnology-  
based cancer theranostic (62-72).  
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Applications of nanotechnology in ovarian  
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.1 Nanotechnology-based photodynamic therapy  
One of the new and relatively widely used fields of  
cancer  
Nanotechnology is an interdisciplinary field and provide  
nanotechnology is photodynamic therapy. In this area, the basis  
of treatment is the use of photosensitizers. In this method, light  
with a certain wavelength is emitted to photosensitizers. Light  
radiation activates photosensitizers, which subsequently  
activates the release of radical oxygen species. The released  
radical oxygen species can induce cell death in tumor cells and  
diminish the rate of angiogenesis. This therapeutic approach  
could be performed locally or systemically. Since this method  
does not suppress the immune system of humans, it can be  
carried out repeatedly by physicians. This method could also  
act as complementary therapy in addition to surgery,  
chemotherapy, or radiotherapy (73, 74). Table 1 shows some of  
the nanostructures used in photodynamic therapy in ovarian  
cancer, as well as other nanoparticles used for diagnostic and  
therapeutic purposes.  
extraordinary opportunities for biological sciences. One of its  
beneficial use is the treatment of cancer, which has received  
much attention due to the growing number of patients. In fact,  
nanotechnology provides early diagnosis, prediction,  
prevention, personalized therapy, and targeted therapy. Some  
researchers believe that nanotechnology paved the way for the  
treatment of various types of cancer. Some of features have  
distinguished nanotechnology from other scientific approaches  
that include: (a) nanosystems and nanostructures can be can be  
used both as a diagnostic and a therapeutic factor at the same  
time; (b) drugs are capable of being targeted for specific cells  
or tissues without causing adverse effects on normal  
cells/tissues; and (c) nanosystems are able to carry several  
therapeutic molecules and therefore provide a platform for  
combination therapy to overcome  
drug-resistance.  
Table 1: Shows some of the nanostructures used in photodynamic therapy  
Function  
Nano particle  
Reference  
Hy-loaded NPs are used for photo dynamic therapy against NuTu-19 cancer cells.  
Nanoencapsulation of Hy in PLA improves the treatment outcome and needs lower doses of  
drugs.  
Hypericin-loaded  
nanoparticles  
(75)  
Gold nanoshell-based complex- anti-HER2 conjugates (nanocomplex) binds specifically to  
OVCAR3 cells. These multiple nanostructures are stimulated by near-IR light to induce cell  
death in ovarian cancer cells through photothermal cancer therapy.  
Nanocomplexanti-HER2  
conjugates  
(76)  
These types of nanostructures exert anti-proliferative activity against SKOV3 ovarian cancer  
cells through photodynamic therapy and the production of reactive oxygen species (ROS).  
SPION-PG-Lys8 / Ce6  
(77)  
(78)  
(79)  
(80)  
(81)  
Zinc oxide (ZnO) nanoparticles conjugated to porphyrin via PDT and subsequently the release  
of reactive oxygen species (ROS) are able to induce selective cytotoxicity against OVCAR-3 in  
ovarian cancer. These nanostructures induce cell death in a dose-dependent manner  
Magnetic iron oxide modified pyropheophorbide-a fluorescence nanoparticles,  
Fe O @SiO @APTES@PPa (FSAP) are used against ovarian cancer cells (SKOV-3). Upon  
3 4 2  
PDT, nanoparticles induce the generation of ROS in cancer cells  
These nanostructures hold promising results in the treatment of a variety of cancer cells,  
including: MDA-MB-231 (human breast cancer), A549 (human lung cancer), and OVCAR3  
(human ovarian cancer). These nanoparticles become activate upon PDT.  
Dendrimer-based nanoplatforms are utilized for cancer-targeted delivery of near-infrared  
photosensitizers, phthalocyanine, and DJ-1 siRNA. These nanostructure is used activated via  
PDT to suppress the DJ-1 protein, one of the key players in resistance of cancer cells to ROS.  
(ZnO-MTAP)  
3 4 2  
Fe O @SiO @APTES@PPa  
FSAP)  
(
Composite Conjugated  
Polymer/Fullerene  
Nanoparticles  
Dendrimer-based  
nanoplatforms  
Coreshellshell  
upconversion nanoparticles  
UCNPs can be used as a theranostic agent. This nanostructure can be used for the combination  
therapy with Pt and PDT against cisplatin resistance.  
(UCNPs)  
(82)  
[NaGdF4:Yb/Nd@NaGdF4:  
Yb/Er@NaGdF4]  
Polymeric micelles of P123 and F127 significantly enhance photodynamic effect with Photofrin  
II® and efficiently deliver photosensitizer in SKOV-3 and MCF-7/WT cells. PDT with  
Photofrin II® loaded in polymeric micelles induces with low hemolytic impact.  
Due to having both multimodal optical imaging and SERS detection with hyperthermia  
capabilities through site specificity, this nanostructure can be introduced as an excellent  
candidate for personalized medicine.  
Polymeric micelles  
(83)  
(84)  
Folic Acid-Conjugated,  
SERS-Labeled Silver  
Nanotriangles  
Hy-loaded NPs of polylactic  
acid  
This nanosystems serves Hy as a natural photosensitizer. Since Hy has a hydrophobic nature,  
polylactic acid polymers are employed to solve this problem.  
(85)  
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