BODIPY-doped silica nanoparticles with reduced dye leakage and enhanced singlet oxygen generation.

Zhuyuan Wang,Changquan Tang,Qingdong Zheng,Shenfei Zong,Yiping Cui,Xuehua Hong

doi:10.1038/srep12602

Abstract

Photodynamic therapy (PDT) is a promising modality for cancer treatment. The essential element in PDT is the photosensitizer, which can be excited by light of a specific wavelength to generate cytotoxic oxygen species (ROS) capable of killing tumor cells. The effectiveness of PDT is limited in part by the low yield of ROS from existing photosensitizers and the unwanted side effects induced by the photosensitizers toward normal cells. Thus the design of nanoplatforms with enhanced PDT is highly desirable but remains challenging. Here, we developed a heavy atom (I) containing dipyrromethene boron difluoride (BODIPY) dye with a silylated functional group, which can be covalently incorporated into a silica matrix to form dye-doped nanoparticles. The incorporated heavy atoms can enhance the generation efficiency of ROS. Meanwhile, the covalently dye-encapsulated nanoparticles can significantly reduce dye leakage and subsequently reduce unwanted side effects. The nanoparticles were successfully taken up by various tumor cells and showed salient phototoxicity against these cells upon light irradiation, demonstrating promising applications in PDT. Moreover, the incorporated iodine atom can be replaced by a radiolabeled iodine atom (e.g., I-124, I-125). The resulting nanoparticles will be good contrast agents for positron emission tomography (PET) imaging with their PDT functionality retained.

Highlights

The manipulation on optical properties of silica NPs is of vital importance because the pure silica NPs themselves barely absorb or emit photons in the visible and IR range in which most light sources, sensors and detectors are active[17,18]
An iodine free chromophore was prepared for comparison
The results clearly demonstrated that the incorporation of heavy atoms leads to enhanced generation of singlet oxygen, which has been verified by a chemical probe method as well as a direct measurement of singlet oxygen luminescence

Summary

Introduction

The manipulation on optical properties of silica NPs is of vital importance because the pure silica NPs themselves barely absorb or emit photons in the visible and IR range in which most light sources, sensors and detectors are active[17,18]. Dipyrromethene boron difluoride (BODIPY) dyes are excellent fluorescent probes and their chemical structures can be modified to incorporate a number of functionalities[23,24,25]. In this context, we design a novel BODIPY dye with a silylated group and two heavy atoms (I). The silylated group is used to covalently encapsulate the dye into silica nanoparticles, and the iodine atoms are used to enhance the singlet oxygen generation of the resulting dye-doped silica NPs. The iodine atoms on the backbone of the silylated BODIPY dye can be used to study the heavy atom effect on the singlet oxygen generation as well as the resultant PDT application. It is expected that the dye leakage of silica NPs will be reduced, which is beneficial for achieving a decreased side effect in PDT

Methods

Results

Conclusion