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. 2019 Jun 5;9(6):860.
doi: 10.3390/nano9060860.

A Photocleavable Amphiphilic Prodrug Self-Assembled Nanoparticles with Effective Anticancer Activity In Vitro

Ji Chen  1 , Guotao Li  2 , Qihong Liu  3 , Yan Liang  4 , Miaochang Liu  5 , Huayue Wu  6 , Wenxia Gao  7
Affiliations

A Photocleavable Amphiphilic Prodrug Self-Assembled Nanoparticles with Effective Anticancer Activity In Vitro

Ji Chen et al. Nanomaterials (Basel). .

Abstract

Accelerating degradation of prodrug is an effective strategy for improving the pharmacological action. A photocleavable amphiphilic prodrug of methotrexate-coumarin derivative-PEG conjugates (MTX-AMC-PEG) with photo-triggered breakage to release clinical drug under laser irradiation was fabricated and self-assembled into nanoparticles for chemotherapy. The nanoparticles exhibited good intracellular uptake and excellent photolysis release of MTX, which resulted in efficient anticancer activity in vitro with laser irradiation. This research provides a way to fabricate photocleavable prodrug nanoparticles with stimuli-triggered drug release behavior.

Keywords: chemotherapy; methotrexate; photocleavable; prodrug; stimuli-responsive release.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
The synthesis of MTX-AMC-PEG conjugate.
Figure 1
Figure 1
The self-assembly of methotrexate-coumarin derivative-PEG (MTX-AMC-PEG) conjugate prodrug into nanoparticles with photoresponsive release via photosolvolysis.
Figure 2
Figure 2
The photosolvolysis process of MTX-AMC-PEG conjugate, (A) HPLC spectra of native MTX (a), blank MTX-AMC-PEG (b) and the products after the photolysis of MTX-AMC-PEG (c); (B) the fluorescence spectra of native MTX, AMC, blank MTX-AMC-PEG, and the remainder after photolysis in PBS (pH 7.4).
Figure 3
Figure 3
(A) DLS results and TEM images (a, before irradiation; b, after irradiation) of the self-assembled MTX-AMC-PEG nanoparticles; (B) The photo-responsive release profiles of MTX from the nanoparticles (1 mg/mL) exposed to laser irradiation (365 nm, 5.0 W, 12 W, 50 W) for 1 min and 3 min in PBS (pH 7.4). Means + SD (n = 3).
Figure 4
Figure 4
The cytotoxicity of MTX-AMC-PEG nanoparticles to 4T1 breast cancer cells, (A) cell viability of 4T1 cancer cells incubated with MTX-AMC-PEG nanoparticles for 48 h; (B) cell viability of 4T1 cancer cells incubated with MTX-AMC-PEG nanoparticles (0.4 µg/mL) under 365 nm (5 W) for 0, 0.5, 1.0, 2.0, and 3.0 min. Sample 1 was the control group of blank cells with laser irradiation (without MTX-AMC-PEG nanoparticles), sample 2 was the cells with MTX-AMC-PEG nanoparticles and different time of laser irradiation; (C) flow cytometry profiles of 4T1 cells incubated with MTX-AMC-PEG nanoparticles for 2 h, 5 h, and 12 h; (D) confocal laser scanning microscopy images of 4T1 cells incubated with MTX-AMC-PEG nanoparticles for 2 h, 5 h, and 12 h.
Figure 4
Figure 4
The cytotoxicity of MTX-AMC-PEG nanoparticles to 4T1 breast cancer cells, (A) cell viability of 4T1 cancer cells incubated with MTX-AMC-PEG nanoparticles for 48 h; (B) cell viability of 4T1 cancer cells incubated with MTX-AMC-PEG nanoparticles (0.4 µg/mL) under 365 nm (5 W) for 0, 0.5, 1.0, 2.0, and 3.0 min. Sample 1 was the control group of blank cells with laser irradiation (without MTX-AMC-PEG nanoparticles), sample 2 was the cells with MTX-AMC-PEG nanoparticles and different time of laser irradiation; (C) flow cytometry profiles of 4T1 cells incubated with MTX-AMC-PEG nanoparticles for 2 h, 5 h, and 12 h; (D) confocal laser scanning microscopy images of 4T1 cells incubated with MTX-AMC-PEG nanoparticles for 2 h, 5 h, and 12 h.
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