Catechins-Modified Selenium-Doped Hydroxyapatite Nanomaterials for Improved Osteosarcoma Therapy Through Generation of Reactive Oxygen Species

Abstract

Osteosarcoma is the most common bone cancer with limited therapeutic options. It can be treated by selenium-doped hydroxyapatite owing to its known antitumor potential. However, a high concentration of Se is toxic toward normal and stem cells whereas its low concentration cannot effectively remove cancer cells. Therefore, the current study was aimed to improve the anticancer activity of Se-HAp nanoparticles through catechins (CC) modification owing to their high cancer therapeutic value. The sequentially developed catechins modified Se-HAp nanocomposites (CC/Se-HAp) were characterized for various physico-chemical properties and antitumor activity. Structural analysis showed the synthesis of small rod-like single phase HAp nanoparticles (60 ± 15 nm), which effectively interacted with Se and catechins and formed agglomerated structures. TEM analysis showed the internalization and degradation of CC/Se-HAp nanomaterials within MNNG/HOS cells through a non-specific endocytosis process. Cell toxicity analysis showed that catechins modification improved the antitumor activity of Se-HAp nanocomposites by inducing apoptosis of human osteosarcoma MNNG/HOS cell lines, through generation of reactive oxygen species (ROS) which in turn activated the caspase-3 pathway, without significantly affecting the growth of human normal bone marrow stem cells (hBMSCs). qPCR and western blot analyses revealed that casp3, p53, and bax genes were significantly upregulated while cox-2 and PTK-2 were slightly downregulated as compared to control in CC/Se-HAp-treated MNNG/HOS cell lines. The current study of combining natural biomaterial (i.e., catechins) with Se and HAp, can prove to be an effective therapeutic approach for bone cancer therapy.

Influence of sonication on the physicochemical and biological characteristics of selenium-substituted hydroxyapatites

“…15,16 In one study, toxicity testing of Se-HAP loaded with the antioxidant catechin in human osteosarcoma cells (MNNG/HOS cell line) found that it exhibited antitumor activity provided by the generation of reactive oxygen species (ROS) via a caspase-3-dependent pathway. 17 This investigation seems to indicate potential for the treatment of bone cancers through the development of antitumor immunity and with minimal side effects to the stem cells, thereby reducing the probability of recurrence. Thus, taking advantage of the potential role of Se-HAP in the reduction of bone cancers, we synthesized an Se-HAP composite via a wet chemical route, in which two different types of samples were collected (after only precipitation and after precipitation followed by sonication).…”

Recent Advances in Nanotechnology-Based Diagnosis and Treatments of Human Osteosarcoma

“…Nanotechnology is a burgeoning research field that has offered groundbreaking solutions for the diagnosis and treatment of OSA [ 21 ]. In this regard, a wide range of nanomaterials has been designed for the targeted treatment of OSA with the least cytotoxicity towards normal human cells [ 22 , 23 ]. As engineered nanomaterials, nanoparticles (NPs) have wide-spread applications in OSA diagnosis and treatment [ 24 , 25 ].…”

Perspective Applications and Associated Challenges of Using Nanocellulose in Treating Bone-Related Diseases

“…Although there are also unclear aspects of nanotechnology restricting its broad-spectrum applications, the inherent unique properties of nanomaterials could help in improving their therapeutic efficacy against osteosarcomas (Turnbull et al, 2018;Zhang et al, 2018b). In addition to different nanoparticles, nanocellulose could also be used to replace the affected bone, like in the form of bone substitutes, as a matrix for impregnation of nanomaterials, and as a drug carrier (Khan et al, 2019) for treating different bone-related diseases. For instance, bisphosphonate-modified nanocellulose (pNC) could be used as a bone substitute for bone regeneration.…”

“…The scaffolds demonstrated in vivo osteoinductivity and bone formation across the damaged site (Osorio et al, 2019a). Besides, nanocellulose could also be modified with anti-osteosarcoma metals or nanoparticles, for instance with selenium, strontium, and arsenic nanoparticles, where nanocellulose could not only function as a carrier for different drugs but also serve as a substitute for the damaged bone tissues (Khan et al, 2019;Luz et al, 2020). Both selenium and arsenic have been widely studied for their anticancer effects, where selenium has been found effective against osteosarcoma when doped with hydroxyapatite (Wang et al, 2016;Khan et al, 2019).…”