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. 2017 Feb 23:7:42978.
doi: 10.1038/srep42978.

Water-Insoluble Photosensitizer Nanocolloids Stabilized by Supramolecular Interfacial Assembly towards Photodynamic Therapy

Yamei Liu  1   2 , Kai Ma  1   2 , Tifeng Jiao  1   2 , Ruirui Xing  1   2 , Guizhi Shen  3 , Xuehai Yan  3
Affiliations

Water-Insoluble Photosensitizer Nanocolloids Stabilized by Supramolecular Interfacial Assembly towards Photodynamic Therapy

Yamei Liu et al. Sci Rep. .

Abstract

Nanoengineering of hydrophobic photosensitizers (PSs) is a promising approach for improved tumor delivery and enhanced photodynamic therapy (PDT) efficiency. A variety of delivery carriers have been developed for tumor delivery of PSs through the enhanced permeation and retention (EPR) effect. However, a high-performance PS delivery system with minimum use of carrier materials with excellent biocompatibility is highly appreciated. In this work, we utilized the spatiotemporal interfacial adhesion and assembly of supramolecular coordination to achieve the nanoengineering of water-insoluble photosensitizer Chlorin e6 (Ce6). The hydrophobic Ce6 nanoparticles are well stabilized in a aqueous medium by the interfacially-assembled film due to the coordination polymerization of tannic acid (TA) and ferric iron (Fe(III)). The resulting Ce6@TA-Fe(III) complex nanoparticles (referenced as Ce6@TA-Fe(III) NPs) significantly improves the drug loading content (~65%) and have an average size of 60 nm. The Ce6@TA-Fe(III) NPs are almost non-emissive as the aggregated states, but they can light up after intracellular internalization, which thus realizes low dark toxicity and excellent phototoxicity under laser irradiation. The Ce6@TA-Fe(III) NPs prolong blood circulation, promote tumor-selective accumulation of PSs, and enhanced antitumor efficacy in comparison to the free-carrier Ce6 in vivo evaluation.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
(A) The structure forms of Ce6 with pH change. (B) Schematic illustration for the fabrication of the Ce6@TA-Fe(III) NPs towards PDT therapy.
Figure 2
Figure 2
(A) TEM image (inset: magnified TEM image, scale bar is 20 nm), (B) AFM image, (C) Size distribution, and (D) Zeta potential of the Ce6@TA-Fe(III) NPs. (E) UV/Vis absorption spectra of the complex NPs, Ce6 suspension solution (pH = 6.0) and TA-Fe(III) complex.
Figure 3
Figure 3
(A) Confocal images of MCF-7 cells before and after irradiation with 635 nm laser (Incubation with Ce6@TA-Fe(III) NPs for 12 h). (B) Selected frames showing the morphological changes of MCF-7 cells treated with Ce6@TA-Fe(III) NPs under laser irradiation in real time (also see Video S2). The blue nuclei of the living cells stained with Hoechst 33342 (Ex = 405 nm), the green fluorescence is resulted from Alexa Fluor® 488 WGA (Ex = 488 nm) and the red fluorescence from Ce6 (Ex = 635 nm). Cell viability of MCF-7 cells incubation with Ce6@TA-Fe(III) NPs or free-carrier Ce6 at different concentrations for 24 h (C) in the dark, (D) upon 635 nm laser irradiation (0.1 W cell−1, 1 min) and followed by further incubation for 24 h. Data are expressed as means ± S.D. based on three measurements.
Figure 4
Figure 4
(A) Time-dependent whole body fluorescence images of MCF-7 tumor-bearing mice treated with free-carrier Ce6 or Ce6@TA-Fe(III) NPs. Red circles indicate tumor sites. (B) Ex-vivo fluorescence images of resected organs and tumor from the mice injected with free-carrier Ce6 or Ce6@TA-Fe(III) NPs (24 h post-injection). (C) Tumor growth curves of different groups after various treatments. (D) Photographs of mice showing the change of tumor after various treatments at different time points.
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