Treatment of breast cancer in vivo by dual photodynamic and photothermal approaches with the aid of curcumin photosensitizer and magnetic nanoparticles

www.nature.com/scientificreports OPEN Treatment of breast cancer in vivo by dual photodynamic and photothermal approaches with the aid of curcumin photosensitizer and magnetic nanoparticles Ali Ashkbar1, Fatemeh Rezaei1*, Farnoosh Attari2* & Saboura Ashkevarian3,4 Breast cancer is a neoplastic disease with a high mortality rate among women. Recently, photodynamic therapy (PDT) and photothermal therapy (PTT) attracted considerable attention because of their minimal invasiveness. The PTT approach works based on hyperthermia generation, and PDT approach employs laser irradiation to activate a reagent named photosensitizer. Therefore, in the current paper, a dual-functioned nanocomposite (NC) was designed for the treatment of breast cancer model in Balb/c mice with the combination of photodynamic and photothermal approaches. Transmission electron microscopy, UV–visible spectroscopy, FTIR, and XRD were employed to validate the nanostructure and silica coating and curcumin (CUR) immobilization on the Fe3O4 nanoparticles. The effect of Fe3O4/SiO2-CUR combined with PDT and PTT was assessed in vivo on the breast tumor mice model, and immunohistochemistry (IHC) was employed to evaluate the expression of apoptotic Bax and Caspase3 proteins. The TEM images, UV–visible absorption, and FTIR spectra demonstrated the successful immobilization of curcumin molecules on the surface of Fe3O4/SiO2. Also, MTT assay confirmed the nontoxic nature of Fe3O4/SiO2 nanoparticles in vitro. In the breast tumor mice model, we have assessed six treatment groups, including control, CUR + PDT, Blue + NIR (near-infrared) lasers, NC, NC + PTT, and NC + PDT + PTT. The tumor volume in the NC + PDT + PTT group showed a significant reduction compared to other groups (p < 0.05). More interestingly, the tumor volume of NC + PDT + PTT group showed a 27% decrease compared to its initial amount. It should be noted that no detectable weight loss or adverse effects on the vital organs was observed due to the treatments. Additionally, the IHC data represented that the expression of proapoptotic Bax and Caspase3 proteins were significantly higher in the NC + PDT + PTT group compared to the control group, indicative of apoptosis. To conclude, our data supported the fact that the NC + PDT + PTT strategy might hold a promising substitute for chemotherapy for the treatment of triple-negative breast cancers. Breast cancer is one of the deadliest diseases among women, which leads to metastasis to vital organs such as the lungs and bones in the body. Approximately one in eight women is encountered with breast cancer in her lifetime1,2. Recent studies on cancer treatment try to find the best and the least risky way to replace the old methods. The major problem in the currently employed cancer treatments is their adverse side effects on the healthy tissues. Nowadays, various methods are being used for the treatment of breast cancer, such as surgery, targeted therapy, hormone therapy, radiation therapy, chemotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT)3. Among these methods, PDT and PTT are valid alternative techniques that recently attracted considerable attention for the treatment of a broad range of diseases, including malignant tumors, because of 1 Department of Physics, K. N. Toosi University of Technology, Tehran, Iran. 2Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. 3Research Institute of Applied Sciences, ACECR, Shahid Beheshti University, Tehran, Iran. 4Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. *email: ; Scientific Reports | (2020) 10:21206 | https://doi.org/10.1038/s41598-020-78241-1 1 Vol.:(0123456789) www.nature.com/scientificreports/ their minimal invasiveness. The PTT approach is a promising strategy that is based on hyperthermia generation utilizing the light energy (NIR laser) to produce heat in the desired tissue4. PDT is a phototherapy approach in which laser irradiation can activate a reagent named photosensitizer (PS) and subsequent production of ROS molecules, which lead to the destruction of the cancerous area5. Generally, photosensitizers play a pivotal role in PDT due to their ability in the production of singlet oxygen via light absorption at the peak wavelength of P S6,7. Photo-active nanostructures are ideal diagnostic detection agents for biosensing8, drug delivery9, and therapy10, which provide significant tools in signal enhancement, photodynamic and photothermal therapy11, and non-linear optical imaging systems12. Moreover, utilizing nanoparticles (NPs) for drug delivery is a growing area in the research which controls the rate of drug release in the desired tissue while circumventing the unwanted delivery to the undesired places9. On the other hand, herbal drugs and their derivative phytocompounds are nowadays known as valuable complementary treatment materials for cancer therapy. Recent reports employed phototherapeutic approaches in combination with nanotechnology and phytochemicals in order to achieve suitable nanocomposite materials for targeted drug d elivery13. Different research groups have studied the treatment of breast cancer with the simultaneous usage of PDT or PTT and nanoparticles. For instance, Stuchinskaya et al., have used targeted PDT employing conjugates of antibody-phthalocyanine-gold nanoparticles for the treatment of HER2 positive breast cancer c ells14. Besides, gold nanorods coated with S iO2 and loaded with Ce6 photosensitizer, in combination with PDT and PTT, induced a strong cytotoxic effect on MCF-7 breast cancer c ells15. Furthermore, Beqa et al. have designed a new hybrid nanomaterial based on gold popcorn-attached carbon nanotubes for appropriate diagnosis and targeted photothermal treatment, which produced irreparable damage to cancer cells within 10 min at 1.5 W/cm2 laser power16. They have shown that the hybrid nanomaterial worked far better compared to the single nanomaterial in response to the photothermal irradiation. Today, the successful application of nanoparticles in combination with photodynamic and photothermal techniques have illustrated drastic improvements in the therapeutic p rocess17,18. Curcumin is an herbal compound with antioxidant and photosensitizer properties, which decreases inflammation and bears anticancer properties19. To our knowledge, curcumin was not employed in a nanostructure in combination with PDT and PTT approaches so far, and the mentioned strategy was not studied in vivo on breast cancer, as well. Therefore, in the current study, a dually functioned nanocomposite was designed for the treatment of breast cancer model in Balb/c mice with the simultaneous employment of photothermal and photodynamic approaches. Here, silicacoated Fe3O4 magnetic nanoparticles which were loaded with curcumin (CUR), as a natural photosensitizer, were injected to the tumor site and CW diode lasers at 450 nm for PDT and at 808 (...truncated)