AS1411 aptamer modified carbon dots via polyethylenimine-assisted strategy for efficient targeted cancer cell imaging.

Tingting Kong,Xiaoxiao Cai,Ronghui Zhou,Yujun Zhang,Bofeng Zhu,Liying Hao

doi:10.1111/cpr.12713

Tingting Kong, Xiaoxiao Cai + Show 4 more

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https://doi.org/10.1111/cpr.12713

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Abstract

ObjectivesCarbon dots (CDs), as a fascinating class of fluorescent carbon nanomaterials, have been proven to be powerful tools in the field of bioimaging and biosensing due to their small size, suitable photostability and favourable biocompatibility. However, the cellular uptake of free CDs lacks selectivity and the same negative charges as cell membranes may cause inefficient cell internalization. In this study, an efficient detecting and targeting nanosystem was developed based on the DNA aptamer AS1411 modified CDs with polyethyleneimine (PEI) as connecting bridge.Materials and methodsHydrothermally prepared CDs were assembled with positive‐charged PEI, followed by conjugation with AS1411 through electrostatic interaction to form CDs‐PEI‐AS1411 nanocomplexes. The CDs, CDs‐PEI and CDs‐PEI‐AS1411 were characterized by transmission electron microscopy (TEM), fourier transform infrared (FTIR) spectra, UV–vis spectra, zeta potential measurements and capillary electrophoresis characterizations. The cytotoxicity investigation of the CDs‐PEI‐AS1411 and CDs‐PEI in both MCF‐7 and L929 cells was carried out by the CCK‐8 assay. The cellular uptake of the CDs‐PEI‐AS1411 was studied with confocal microscopy and flow cytometry.ResultsThe as‐prepared nanosystem possessed good photostability and no obvious cytotoxicity. On the basis of the confocal laser scanning microscope observation and the flow cytometry studies, the cellular uptake of CDs‐PEI‐AS1411 nanosystem in MCF‐7 cells was significantly higher than that of L929 cells, which revealed the highly selective detection ability of nucleolin‐positive cells.ConclusionsThe results of this study indicated that the CDs‐PEI‐AS1411 nanosystem had a potential value in cancer cell targeted imaging.

Highlights

Carbon dots (CDs) have received great attention in bio‐related ap‐ plications such as biosensing and bioimaging due to their small size, low toxicity, good biocompatibility and good stability
It is well known that AS1411 is a common aptamer with 26‐mer oligonu‐ cleotide, which can bind to the nucleolin that is highly expressed on the surface of most cancer cells.[11]
The results showed that CDs‐PEI‐AS1411 nanosystem possessed higher cellular uptake efficiency in MCF‐7 cells than L929 cells

Summary

Introduction

Carbon dots (CDs) have received great attention in bio‐related ap‐ plications such as biosensing and bioimaging due to their small size, low toxicity, good biocompatibility and good stability. CDs modified with small oligonucleotide ligands (aptamer), peptides or small molecules have been widely used in targeted fluorescent imaging, drug delivery and cancer therapy.[1,2,3,4,5,6] Among the numerous targeted agent, aptamer possessed chemical stability, non‐immuno‐ genicity and easy synthesis, which garnered a lot of attention.[7,8,9,10] It is well known that AS1411 is a common aptamer with 26‐mer oligonu‐ cleotide, which can bind to the nucleolin that is highly expressed on the surface of most cancer cells.[11] As a result, AS1411 is a promising candidate for precisely targeting.[12,13,14,15,16] for AS1411 favoured fluorescence targeting imaging, the relatively complex strategy of chemical coupling is usually adopted to connect imaging agent with AS1411, which may result in poor targeting ability. The imag‐ ing agent conjugated with negative charged aptamer AS1411 always exhibit the same negative charge as cell membrane, which may affect the efficiency of cellular uptake ascribe to the electrostatic repulsion

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