A Targeted Nanoprobe Based on Carbon Nanotubes-Natural Biopolymer Chitosan Composites

Baoyan Wu,Na Zhao

doi:10.3390/nano6110216

Abstract

A novel targeting theranostic nanoprobe based on single-walled carbon nanotubes (SWCNTs)-natural biopolymer chitosan composites was developed for cancer cell targeting imaging and fluorescence imaging-guided photodynamic therapy. First, chitosan was respectively conjugated with a tumor-homing molecule folic acid, or a photosensitizing drug pyropheophorbide a using a water-soluble carbodiimide coupling chemistry. Chitosan was fluorescently labeled by fluorescein isothiocyanate via the covalently linkage of the isothiocyanate group with the amino group. Second, SWCNTs were sonicated in the functional chitosan aqueous solution for 6 h at room temperature in order to obtain the nanoprobe (PPa/FITC-SWCNT-FA). The as-prepared nanoprobe has been characterized with transmission electron microscope, confocal microscopy, and cell cytotoxicity tests. Chitosan was decorated onto SWCNTs resulting in the water-dispersible PPa/FITC-SWCNT-FA, and can be selectively transported inside folate receptor-positive tumor cell with good targeting imaging. PPa/FITC-SWCNT-FA exhibited low dark toxicity about 7%–13%, and high phototoxicity about 60%–74% against HeLa cells upon a 635 nm laser irradiation, indicating satisfying biocompatibility and antitumor activity. These results suggest the study could offer a feasible alternative to presently available nanoparticle-based theranostic agents.

Highlights

Photodynamic therapy (PDT) is an alternative tumor-ablative and function-sparing oncologic intervention [1]
The surface of chitosan was first grafted with folic acid (FA), PPa, and fluorescein isothiocyanate (FITC) to form functional chitosan which was denoted as CHIT-FA, CHIT-FITC, and CHIT-PPa, respectively
single-walled carbon nanotubes (SWCNTs) was used as drug delivery carriers, PPa as a photosensitizing drug, FA as a tumor-homing molecule, and FITC as a fluorescence imaging agent, affording the resulting probe used for cancer cell targeting imaging and fluorescence imaging-guided photodynamic therapy

Summary

Introduction

Photodynamic therapy (PDT) is an alternative tumor-ablative and function-sparing oncologic intervention [1]. PDT is a clinically approved, minimally invasive therapeutic procedure mediated by the production of singlet oxygen or reactive oxygen species generated from photosensitizer molecules with an appropriate excitation light to cause cell death and tissue destruction [2,3,4]. Compared to conventional cancer therapy, the major advantages of PDT are that a photosensitizer itself is of low toxicity in the dark, and activation by light alone permits minimal damage to non-specific tissues [5,6,7]. Hydrophobic nature of most photosensitizers results in strong self-aggregation in aqueous media, which significantly reduces their photodynamic efficacy because only monomeric species are appreciably photoactive [11]. Photosensitizer-carrying nanoparticles could increase the water solubility of photosensitizer molecules, enhance their tumor accumulation, and improve the therapeutic efficacy and specificity of PDT [6]

Methods

Results

Conclusion