α-Tocopheryl Succinate-Based Polymeric Nanoparticles for the Treatment of Head and Neck Squamous Cell Carcinoma

Abstract

The aim of this work is to study, in an in vitro head and neck squamous cell carcinomas model the anti-angiogenic and anti-migratory properties of self-assembled polymeric nanoparticles (NPs) with demonstrated selective anticancer activity. The NPs are based on α-tocopheryl succinate (α-TOS) encapsulated in the hydrophobic core of the NPs. We analyzed the effect of the newly synthetized α-TOS-loaded NPs in proliferating endothelial cells and hypopharynx carcinoma squamous cells and measured markers of angiogenesis, apoptosis and reactive oxygen species (ROS). α-TOS-loaded NPs suppressed angiogenesis by inducing accumulation of ROS and inducing apoptosis of proliferating endothelial cells. These NPs also decrease the number and quality of capillary-like tubes in an in vitro three-dimensional (3D) experiment, decrease the production of the pro-angiogenic vascular endothelial growth factor and down-regulate the expression of its receptor. The anti-migratory efficacy of α-TOS is corroborated in hypopharynx carcinoma cells by decreasing the secretion of matrix metalloproteases 2 and 9 (MMP-2 and MMP-9) and inhibiting cell migration. These results confirm that α-TOS-based NPs not only present anticancer properties, but also antiangiogenic properties, therefore making them promising candidates for multi-active combinatorial anticancer therapy.

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

“…Nanomedicine is an emerging form of treatment that is dedicated to alternative drug delivery and improved therapeutic efficacy, while reducing harmful side Oxidative Medicine and Cellular Longevity effects on normal tissues. New nanoparticle systems with highly flexible and rapid drug design and production capabilities can be created, which can be designed based on the genetic characteristics of tumors; therefore, making the drug selection for individual patient treatment and overcoming multiple forms of multidrug resistance look promising and open up new prospects for cancer treatment [262][263][264][265][266][267][268]. The effect of metal nanoparticles on ROS concentration has been shown to play a role in both radiosensitization and radioprotection.…”

Tocotrienol: An Underrated Isomer of Vitamin E in Health and Diseases

“…Another study revealed that δ-tocotrienol exhibited potential against both melanoma and its associated stem cells [228,229], while displaying suppressive action on prostate cancer stem-like cells [230]. Recent findings also indicated that tocotrienols displayed antiangiogenic protein expression of VEGF in colorectal cancer [231], malignant mesothelioma [232], breast cancer [233], ovarian carcinoma [234], and head and neck squamous cell carcinoma [235]. All these studies provide ample evidence of the role of tocotrienol in arresting tumour growth by inhibiting angiogenesis.…”

Molecular Mechanisms of Action of Tocotrienols in Cancer: Recent Trends and Advancements

“…Shiozawa et al, have also elegantly illustrated the cytotoxic effect of redox-silent analogue of tocotrienol in inhibiting survival of PC3 cells (androgen-independent prostate cancer (PCa) cell line) under hypoxia, through inhibition of Fyn/HIF-1α signaling cascade, which may lead to the establishment of a new effective therapy for PCa [87]. In addition, pre-clinical data from numerous other studies have also reported that γ-T3 alleviates angiogenic protein expression (VEGF) in colorectal cancer [88], malignant mesothelioma [89], breast cancer [90], ovarian carcinoma [91], head and neck squamous cell carcinomas [92], and other cancers. Thus, in view of the above scientific reports, tocotrienols appear to be important therapeutic molecules for improvement of prognosis in cancer patients by targeting angiogenesis.…”