Molecular-Based Nanoplatform Leads to the Formation of a Self-Indicating Responsive Drug Delivery System

Abstract

We report the design and biological evaluation of a nanoplatform featuring controllable aggregation-induced emission (AIE) behavior. The free rotation of benzene rings (4-(1,2,2-triphenylvinyl) benzaldehyde) largely suppresses fluorescence in the pure organic phase. However, water-induced molecular aggregation enhances the fluorescence signal. The delivery system follows the membrane-cytoplasm-nucleus route and it leads to apoptosis in two cancer cells (U937 cells and Hela cells). The AIE moiety accumulates in the cytoplasm, emitting a bright-blue signal, but the anticancer drug doxorubicin selectively targets the nucleus with unique red emission. The current noninvasive method with DOX-triggered apoptosis holds promise for tumor diagnosis and real-time imaging.

Keywords: cellular imaging; fluorescence; nanoplatform; therapy.

Figure 1

Structure of TPE-CHO and the preparation of TD NPs and the subsequent utilization of the TD NPs for cell therapy. Different color of cells indicates the co-localization of TPE-CHO with lysosomes (blue to green), the internal red fluorescence from DOX corresponds to nuclear staining.

Figure 2

Emission changes of TPE-CHO (25 μM) in DMSO/water mixtures with different concentrations of water.

Figure 3

Fluorescence spectra of TD NPs (25 μM) with different excitation wavelengths (Ex = 370 nm and 490 nm) at pH 7.4 and 5.0.

Figure 4

TEM images of TPE-CHO NPs (A) and TD NPs (B) (pH = 7.4).

Figure 5

Cell viability of TPE-CHO NPs, DOX, and TD NPs towards to U937 cells.

Figure 6

Representative distribution of U937 (A,C) and Hela cells (B,D) obtained by Annexin V-APC/PI staining experiments. Cells of (A,B) were treated with 25 μM TPE-CHO NPs, and (C,D) were treated with 25 μM TD NPs. Color dots from blue to red refer to cell density increase.

Figure 7

Confocal microscopy images of U937 cells cultured with TD NPs (25 μM), free DOX (5 μM), and TD NPs (25 μM) and co-stained with Lysotracker Green after a 4 h incubation. Different color of cells indicates the co-localization of TPE-CHO with lysosomes (blue to green), the internal red fluorescence from DOX corresponds to nuclear staining.

Figure 8

Confocal microscopy images of Hela cells cultured with TD NPs (25 μM), free DOX (5 μM), and TD NPs (25 μM) and co-stained with Lysotracker Green after a 4 h incubation. Different color of cells indicates the co-localization of TPE-CHO with lysosomes (blue to green), the internal red fluorescence from DOX corresponds to nuclear staining.