Mitochondrially Targeted Nanoparticles Based on α‐TOS for the Selective Cancer Treatment

Abstract

The aim of this work is the preparation of an active nanovehicle for the effective administration of α‐tocopheryl succinate (α‐TOS). α‐TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo‐block copolymers of N‐vinyl pyrrolidone and a methacrylic derivative of α‐TOS. These well‐defined spherical NPs have sizes below 165 nm and high encapsulation efficiencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells and nonmalignant epithelial cells, demonstrating that the presence of additional α‐TOS significantly enhances its antiproliferative activity; however, a range of selective concentrations is observed. These NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (via caspase‐9). Both loaded and unloaded NPs act via complex II and produce high levels of reactive oxygen species that trigger apoptosis. Additionally, these NPs effectively suppress the vascular endothelial growth factor (VEGF) expression of human umbilical vein endothelial cells (HUVECs). These results open the possibility to use this promising nanoformulation as an α‐TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free α‐TOS administration.

Photothermal and photodynamic activity of polymeric nanoparticles based on α-tocopheryl succinate-RAFT block copolymers conjugated to IR-780

“…Relatively slow uptake of α-TOS by malignant cells, which relies on passive diffusion, is a limiting point for its efficient delivery[29, 30]. This drawback can be overcome using NPs derived from MTOS, that can entrap additional α-TOS in their inner core to significantly increase the amount of drug that reaches the cell interior and thereby improving its cytotoxic potential[31]. Incorporation of IR-780 iodide on the surface of the polymeric NPs derived from MTOS may increase the selectivity of these nanosystems.…”

Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and α-tocopheryl succinate enhance anti-tumor effect in vivo

“…18 The main obstacle for the successful application of α-TOS-based clinical treatments is the hydrophobic nature of this drug that significantly reduces its bioavailability and therapeutic activity. 19 In addition, the intravenous or intraperitoneal administration of α-TOS in an organic phase or oil emulsion can cause important side effects, such as the formation of aggregates as a result of drug mixing with blood plasma, inflammation and embolization processes. 20 In recent years, the drug-loaded polymeric nanoparticles (NPs) offer bright promise for cancer therapy.…”

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

“…Despite all these properties, the hydrophobic nature of the drug, which significantly reduces its bioavailability and therapeutic activity, is the main obstacle for the successful application of α-TOS-based clinical treatments. Our group has incorporated this molecule into nanovehicles of appropriate hydrodynamic properties in order to improve the biological activity of α-TOS [ 14 , 15 , 16 , 17 ]. In this sense, the methacrylic derivative of α-TOS was synthesized and copolymerized forming amphiphilic macromolecules that were able to self-assemble in aqueous media forming surfactant-free nanoparticles (NPs).…”

“…In this sense, the methacrylic derivative of α-TOS was synthesized and copolymerized forming amphiphilic macromolecules that were able to self-assemble in aqueous media forming surfactant-free nanoparticles (NPs). The hydrophilic segment of the copolymers was mainly based on N -vinyl pyrrolidone (VP), and the hydrophobic segment mostly incorporated MTOS (poly(VP- co -MTOS)(89:11)) [ 14 , 17 ]. Unloaded NPs (NP-0) presented in vitro anticancer activity in different cancerous cell lines and had the capacity to selectively reduce cell viability of proliferating ECs.…”

“…Unloaded NPs (NP-0) presented in vitro anticancer activity in different cancerous cell lines and had the capacity to selectively reduce cell viability of proliferating ECs. Moreover, α-TOS encapsulation in the inner core of the NPs (NP-10) enhanced the pro-apoptotic activity of these nanoassemblies on hypopharynx carcinoma squamous cells (FaDu) [ 17 ]. For these reasons, the aim of this work is to analyze the in vitro anti-angiogenic and anti-invasive effect of these recently synthetized α-TOS-based NPs (NP-0 and NP-10).…”