Multifunctional decoration of alpha-tocopheryl succinate-based NP for cancer treatment: effect of TPP and LTVSPWY peptide

Abstract

Active targeting not only of a specific cell but also a specific organelle maximizes the therapeutic activity minimizing adverse side effects in healthy tissues. The present work describes the synthesis, characterization, and in vitro biological activity of active targeting nanoparticles (NP) for cancer therapy based on α-tocopheryl succinate (α-TOS), a well-known mitocan, that selectively induces apoptosis of cancer cells and proliferalting endothelial cells. Human epidermal growth factor receptor 2 (HER2) targeting peptide LTVSPWY (PEP) and triphenylphosphonium lipophilic cation (TPP) were conjugated to a previously optimized RAFT block copolymer that formed self-assembled NP of appropriate size for this application and low polydispersity by self-organized precipitation method. PEP and TPP were included in order to target not only HER2 positive cancer cells, but also the mitochondria of these cancer cells, respectively. The in vitro experiments demonstrated the faster incorporation of the active-targeting NP and the higher accumulation of TPP-bearing NP in the mitochondria of MDA-MB-453 HER2 positive cancer cells compared to non-decorated NP. Moreover, the encapsulation of additional α-TOS in the hydrophobic core of the NP was achieved with high efficiencies. The loaded NP presented higher cytotoxicity than unloaded NP but preserved their selectivity against cancer cells in a range of tested concentrations.

Mitochondria Targeting and Destabilizing Hyaluronic Acid Derivative-Based Nanoparticles for the Delivery of Lapatinib to Triple-Negative Breast Cancer

“…31,32 The TPP and TS included in HA-TS-TPP NPs may exert mitochondria targeting and disrupting activities and may contribute to the apoptosis of cancer cells. 33,34 In Annexin V-FITC and PI-based apoptosis assay, the sum of the UR and LR panels was used to count the population of the late and early apoptosis stages. Blank HA-TS NPs and HA-TS-TPP NPs also exhibited elevated apoptotic inducing capability compared to the control (no treatment) group (p < 0.05).…”

Amphiphilic polymeric nanoparticles encapsulating curcumin: Antioxidant, anti-inflammatory and biocompatibility studies

“…Our group has a wide experience in the synthesis of vitamin E derived copolymers for different applications e.g. acrylic bone cements [40], anti-cancer treatment [41][42][43][44] or the treatment of sensorineural hearing loss [45][46][47]. Antecedents of vitamin E based copolymer NPs have been reported by our group, i.e.…”

Drug Transporters

“…In a recently published study, Palao-Suay et al successfully synthesized active targeted polymeric NPs conjugating a bromide derivative of triphenylphosphonium lipophilic cation and peptide ligand LTVSPWY to amphiphilic PEG-b-poly-MTOS. The peptide ligand LTVSPWY strongly and preferentially interacts with human EGFR of cancer cells, without binding to nonmalignant mammary epithelial cells (Palao-Suay et al 2017).…”