Cyclometallic iridium-based nanorods for chemotherapy/photodynamic therapy
Graphical abstract
Schematic illustration of Ir-PTX NRs for chemo-photodynamic therapy.
Introduction
Malignant tumors remain huge threat to human health. As the most commonly used therapy against tumor, chemotherapy has extended the lives of millions of patients [1]. The chemotherapy drugs, such as doxorubicin (DOX), cisplatin (CDDP) and paclitaxel (PTX), can be rapidly taken up by cancer cells and exert anticancer effect. However, chemotherapy inevitably causes serious side effects because of its low targeting efficiency, nonspecific drug distribution and toxicity to normal tissues. Compared with chemotherapy, photodynamic therapy (PDT) is a typical noninvasive light-excited treatment paradigm, which uses specific light to stimulate the photosensitizer (PS) to produce high-cytotoxic singlet oxygen (1O2) for killing cancer cells. Although PDT has great potential in cancer therapy with its low toxicity, selectively killing cancer cells, there are still challenges blocking the broad applications of PDT [2].
The combination of chemotherapy and PDT has a synergistic effect to improve therapeutic efficiency and overcome drug resistance [3]. PDT can assist chemotherapy and enhance targeting specificity, and chemotherapy can eliminate residual tumor cells after PDT and inhibit the regeneration of damaged blood vessels. Huang and co-workers have designed supramolecular triangles containing both boron dipyrromethene (BODIPY) for PDT and platinum(II) for chemotherapy [4].
It can be seen from the above work that the combination of PDT and chemotherapy shows better cancer treatment than monotherapy. Hence, we synthesized a novel photosensitizer Ir-PTX by conjugating Cyclometalated Ir(III) complexes with Paclitaxel (PTX). Cyclometalated Ir(III) complexes are widely used photosensitizers with high biocompatibility, large Stokes’ shifts and good photostability, which can generate sufficient singlet oxygen in the tumor cells [5]. Paclitaxel (PTX) has long been the first-line anticancer drug in the clinic and been studied for the treatment of various cancers [6]. In the present study, Ir-PTX can self-assemble into nanorods (Ir-PTX NRs). Morphology plays an important role in the performance of nanomaterials, and rod-shaped particles appear to be more favorably engulfed by cells compared to spherical counterparts. Our experiments showed Ir-PTX NRs could generate 1O2 to kill cells, performing greater cytotoxicity than chemotherapy alone. We believe Ir-PTX NRs display synergistic effect for chemo-photodynamic therapy in vitro.
Section snippets
Materials and methods
The Ir-PTX NRs were prepared via precipitation method. Later, the nanocomposites were characterized to evaluate their morphological, structural and spectroscopic properties. Furthermore, the 1O2 production of NRs and the release of PTX in solution were assessed. Moreover, cellular uptake was studied by confocal laser scanning microscopy (CLSM) and the cytotoxicity were evaluated by MTT assay. All details of these experimental procedures were declared in the supporting information.
Synthesis and preparation of nanorods
The synthesis process has given in Fig. S1. We have obtained a novel photosensitizer and prodrug Ir-PTX. The structure of Ir-PTX has been confirmed by 1H NMR spectroscopy (Fig. S5) and MALDI-TOF MS (Fig. S6). And the structures of other composites were confirmed by 1H NMR Supplementary figure 2, Supplementary figure 3, Supplementary figure 4).
A simple precipitation method was used to prepare the Ir-PTX NRs (see the Supporting Information). The length of nanorods was about 210 nm and the width
Conclusion
We have synthesized a novel photosensitizer and prodrug Ir-PTX, which can self-assemble into nanorods Ir-PTX NRs. After being taken up by cells, the NRs could generate sufficient singlet oxygen at the presence of light for photodynamic therapy. The anticancer drug PTX could be released for chemotherapy by the cleavage of ester bonds in cells. All obtained data from in vitro showed Ir-PTX NRs exhibited an excellent phototoxicity and chemotoxicity. The combination of PDT and chemotherapy can
CRediT authorship contribution statement
Wan Liu: Investigation, Writing - original draft. Nan Song: Conceptualization, Methodology. Yuanyuan Li: Data curation. Yang Liu: Data curation. Li Chen: Supervision. Shi Liu: Supervision. Zhigang Xie: Supervision.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgement
This work was supported by the National Natural Science Foundation of China (Projects 51973025 and 21474012).
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