Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells.

Sanjay Tiwari,Nishith A Chudasama,Jayant Sarolia,Vrushti Kansara,Debes Ray,Vinod K Aswal,Pratap Bahadur,Kamalesh Prasad

doi:10.3390/polym12102258

Abstract

This study reports targetable micelles developed after covalent functionalization of α-tocopheryl polyethylene glycol succinate (TPGS) with amino phenylboronic acid (APBA). Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopic results showed successful attachment of APBA to the hydrophilic segment of TPGS. Dynamic light scattering and small-angle neutron scattering studies revealed that the conjugate self-assembled in water to produce spherical core-shell micelles (14–20 nm) which remained stable against temperature (ca. 25–45 °C) and pH changes. The micelles could solubilize a high payload of paclitaxel (PLX) without exhibiting changes in the average size. However, at the saturation solubility, drug molecules migrated from the core to the shell region and engaged with APBA groups via π–π stacking interaction. Confocal microscopy and cell sorting analyses verified the effective translocation ability of TPGS-APBA micelles in sialic acid (SA) expressing MDA-MB-453 cells. At equivalent PLX dose, TPGS-APBA micelles showed about a twofold improvement in apoptotic death among the cells exposed for 2 h. Our findings indicate that the attachment of APBA can be a potential strategy for improving the intra-cellular localization of carriers among cancer cells expressing SA residues.

Highlights

The terminal position of cell membrane glycoproteins and glycolipids is occupied byN-acetylneuraminic acid derivatives
We describe the attachment of 3-amino phenylboronic acid (APBA) to d-α-tocopheryl polyethylene glycol succinate (TPGS), a nonionic surfactant composed of polyethylene glycol (PEG, molecular weight—1000 Da) linked to α-tocopherol via a succinate diester bond
The show a comparison between apoptotic ability of data show a comparison between apoptotic ability of PLX delivered in TPGS (B) and TPGS-APBA (C)

Summary

Introduction

The terminal position of cell membrane glycoproteins and glycolipids is occupied by. The latter is dominated by sialic acid (SA), a nine carbon sugar which imparts a net negative charge to cells [1,2]. Cancer progression correlates with the addition and branching of terminal SA groups (hypersialylation) over the cell surface. Triggered through upregulated action of cytosolic sialyltransferases (ST), hypersialylation configures the microenvironments conducive to cancer cell progression, metastasis and immune evasion [3,4]. Therapeutic strategies aimed at blocking SA synthesis (ST inhibitors) or cleavage of SA branching with neuraminidase have been criticized for poor transcellular permeation and low efficacy [5,6,7]. The high binding affinity of phenylboronic acid (PBA) to sialylated epitopes has been explored for selective targeting of bioactive molecules to tumor cells.

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Discussion

Conclusion