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.2017 Nov;24(1):1419-1428.
doi: 10.1080/10717544.2017.1378939.

Enhancement of radiotherapy efficacy by pleiotropic liposomes encapsulated paclitaxel and perfluorotributylamine

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Enhancement of radiotherapy efficacy by pleiotropic liposomes encapsulated paclitaxel and perfluorotributylamine

Xing Jiang et al. Drug Deliv.2017 Nov.

Abstract

Paclitaxel (PTX) is widely used as a radiosensitizer in the clinical treatment of cancer. However, the efficacy of chemoradiotherapy is limited by the hostility of the tumor microenvironment such as hypoxia. To overcome this constraint, we designed pleiotropic radiotherapy sensitized liposomes containing perfluorotributylamine (PFTBA) and PTX. The results showed that liposomes significantly accumulated in the tumor site. PFTBA in liposomes dramatically reversed tumor hypoxia and improved the sensitivity of tumor radiotherapy. PTX in liposomes blocked the cell cycle of tumor cells in the radiation-sensitive G2/M phase, which was even greater when combined with PFTBA. In vitro and in vivo tumor treatment further demonstrated remarkably improved therapeutic outcomes in radiotherapy with such biocompatible liposomes. In conclusion, the pleiotropic liposomes encapsulated PFTBA and PTX provide significant radiotherapy sensitization and show promise for future application in clinical medicine.

Keywords: Chemoradiotherapy; hypoxia; liposomes; paclitaxel; perfluorotributylamine.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Preparation and characterization of liposomes. (a) Schematic of preparation of lip(PFTBA + PTX). (b) Photograph showing of lip(PFTBA + PTX). (c) Transmission electron microscopy visualization of lip(PFTBA + PTX). (d) Dynamic light scattering measurement of lip(PFTBA + PTX). (e) The O2 concentration in different solutions of NS, lip(PTX), lip(PFTBA) and lip(PFTBA + PTX).
Figure 2.
Figure 2.
Cellular uptake of liposomesin vitro. Confocal laser-scanning microscopy of CT26 cells after 2 h co-incubation with lip(IR775) or free-IR775. IR775 was red and the cancer-cell nucleus were stained blue with DAPI (bar =50 μm).
Figure 3.
Figure 3.
Radiosensitizationin vitro. (a, b) Effect of NS, lip(PTX), lip(PFTBA) and lip(PFTBA + PTX) on cell-cycle in CT26 cells for 24 h. (c) Clonogenic survival assay carried out after eight days of incubation. (d) Cell apoptosis detected by PI staining at 48 h after being exposed to various conditions. Data are shown as mean ± SD (n = 3, ***p < .001).
Figure 4.
Figure 4.
Behaviorin vivo. (a)In vivo dynamic fluorescence imaging after intravenous injection of lip(IR775) or free-IR775. (b) Fluorescence intensity in tumor site by IVIS Living Imaging Software (**p < .01). (c)Ex vivo fluorescence images and fluorescence intensity of major organs and tumor of lip(IR775) group at 72 h postinjection (***p < .001). (d) Quantitative analysis of PTX in tumors after intravenous injection of lip(PFTBA + PTX) (*p < .05).
Figure 5.
Figure 5.
Antitumor efficacyin vivo. (a) HIF-1α in tumor tissue identified by immunohistochemical analysis after intravenous injection (staining of HIF-1α, brown; nucleus of cancer cells, blue) (bar =50 μm). (b) TUNEL staining for apoptosis in tumor sections. DAPI counterstaining indicates the tumor nuclear region (bar = 50 μm). H&E staining for pathological changes in tumor sections (bar =50 μm). γ-H2AX staining for double-strand DNA breaks (staining of γ-H2AX, brown; nucleus of cancer cells, blue) (bar =50 μm). (c) Relative tumor volume of different groups of mice after various treatment. Data are expressed as mean ± SD (n = 5 mice per group, **p < .01). (d) Changes of body weight of mice in different groups during treatments. Data are expressed as mean ± SD (n = 5 mice per group).
Figure 6.
Figure 6.
Representative H&E-stained slices images of major organs in each group at the end of the experiment (①NS; ②Lip(PFTBA); ③Lip(PTX); ④Lip(PFTBA + PTX); ⑤NS + RT; ⑥Lip(PFTBA)+RT; ⑦Lip(PTX)+RT; ⑧Lip(PFTBA + PTX)+RT (bar =200 μm).
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