Development of novel radiochemotherapy approaches targeting prostate tumor progenitor cells using nanohybrids

Abstract

Many tumors including prostate cancer are maintained by cancer stem cells (CSCs), which might cause tumor relapse if not eradicated during the course of treatment. Specific targeting or radiosensitization of CSCs bear promise to improve tumor curability by synergistic effects in combination with radiotherapy. Carbon nanotubes (CNTs) can be used as promising drug delivery systems for anticancer drugs such as the flavonoid catechin. Catechin is an extensively studied active ingredient of the different plants, including green tea, and it is widely recognized as co-adjuvant in cancer therapy. Here we describe the synthesis of biocompatible, catechin-loaded and gelatin-conjugated CNTs (Gel_CT_CNTs) with anticancer properties and demonstrate their potential for the eradication of prostate CSCs in combination with X-ray irradiation. Gel_CT_CNTs showed a significant enhancement of in vitro anticancer activity as compared to catechin alone. Moreover, treatment of prostate cancer cells with Gel_CT_CNT nanohybrids inhibited the tumorigenic cell population defined by a high aldehyde dehydrogenase (ALDH) activity. A combination of X-ray irradiation and treatment with Gel_CT_CNTs caused a decrease in the protein level of stem cell-related transcription factors and regulators including Nanog, Oct4 and b-catenin and led to an increase of cancer cell radiosensitivity as demonstrated by clonogenic and spherogenic cell survival assays. Taken together, our results suggest that a combination of irradiation and Gel_CT_CNTs can be potentially used for the radiosensitization and eradication of prostate CSC populations.In Europe, prostate cancer is the third most common cause of cancer and among the leading causes of cancer-related deaths in men. Radiotherapy is one of the key treatments for prostate cancer along with surgery, chemotherapy and hormone therapy.1 A significant proportion of men is diagnosed with curable localized prostate cancer. However, successful treatment of the patients by radiotherapy depends on tumor radiosensitivity and the tolerance of the surrounding normal

Anti-Cancerous Potential of Polyphenol-Loaded Polymeric Nanotherapeutics

“…Functional nanohybrids Table 6 have also been prepared by developing covalent bonds between the polyphenol and the polymer through a radical reaction. In this regard, catechin–gelatin conjugate [ 137 , 138 ] and quercetin–methacrylic acid conjugate [ 139 , 140 ] were used as the coating material for multi-walled carbon nanotubes. The obtained nanotherapeutics were found to have enhanced anticancer activity in HeLa cancer cells, compared with the free flavonoids [ 137 , 139 ].…”

Nanoparticles as Theranostic Vehicles in Experimental and Clinical Applications—Focus on Prostate and Breast Cancer

“…Regarding PCa and BC applications utilizing carbon-based NPs there is an increasing number of publications during the last couple of years, both for imaging and therapy but also for different kind of electrochemical biosensor systems [226,227,228,229,230,231,232,233,234]. For instance, regarding PCa, Heydari-Bafrooei et al and Pan et al have both developed different kind of CNT-based biosensor systems able to detect prostate specific antigen (PSA) in serum and vascular endothelial growth factor (VEGF) and PSA in serum, respectively, for early diagnosis of PCa [227,229].…”

Therapeutic efficacy of nanomedicines for prostate cancer: An update

“…Catechin is in the family of polyphenolic flavonoids, and catechin and its derivatives (2)-epigallocatechin-3-gallate, (2)-epigallocatechin, (2)-epicatechin-3-gallate, and (2)-epicatechin inhibit cancer cell proliferation, suppress tumor growth and metastasis, and sensitize tumors to various chemotherapy drugs and radiotherapy [ 44 45 46 ]. Recently, a study showed that biocompatible catechin-loaded and gelatin-conjugated carbon nanotubes have good anticancer properties with the potential for targeting prostate PCa stem cells in combination with x-ray irradiation [ 47 ].…”