An ultra-stable redox-controlled self-assembling polypeptide nanotube for targeted imaging and therapy in cancer

Gitanjali Asampille,Abhijith Shettar,Brijesh Kumar Verma,Paturu Kondaiah,Steven A Rosenzweig,Monalisa Swain,Hanudatta S Atreya

doi:10.1186/s12951-018-0427-1

Abstract

We introduce a self-assembling polypeptide-based nanotube system having the ability to specifically target cancer cells. The nanotubes target the cancer cell surface through integrin engagement with the help of multiple RGD units present along their surface. While the nanotubes are non-toxic towards cells in general, they can be loaded with suitable drugs to be released in a sustained manner in cancer cells. In addition, the nanotubes can be utilized for cellular imaging using any covalently tagged fluorescent dye. They are stable over a wide range of temperature due to intermolecular disulphide bonds formed during the self-assembly process. At the same time, presence of disulphide bonds provides a redox molecular switch for their degradation. Taken together this system provides a unique avenue for multimodal formulation in cancer therapy.

Highlights

The development of multimodal systems combining imaging and drug delivery components have come into focus due to their theranostic efficacy [1]
The oligomerization was tracked in a time-dependent manner using, in parallel, Sodium Dodecyl Sulfate–Polyacrylamide Gel Electrophoresis (SDS-PAGE) (Fig. 1a) and twodimensional (2D) nuclear magnetic resonance (NMR) spectroscopy (Fig. 1b, c)
The SDS-PAGE profile shown in Fig. 1a depicts the progress of oligomerization during self-assembly at initial stages at room temperature and reveals the appearance of a dimer on day 1, which becomes relatively more populated on day 2 and higher order multimeric species are visible on day 4

Summary

Introduction

The development of multimodal systems combining imaging and drug delivery components have come into focus due to their theranostic efficacy [1]. To achieve this, targeted delivery systems have been proposed [6]. The Arg-Gly-Asp (RGD) is the most widely studied and used peptide for decorating biomaterials to achieve specific targeting in the biomedical field [7,8,9,10,11,12]. This tripeptide has proved to be very effective in binding integrin receptors as efficiently as the principal integrinbinding domains within extracellular matrix (ECM) proteins such as fibronectin, vitronectin and fibrinogen [13]

Methods

Results

Conclusion