We demonstrate a nanotechnology approach for the development of cancer-cell-specific subcellular organelle-targeted drug nanocarriers based on photostable nanodiamonds (ND) functionalized with folic ...acid and mitochondrial localizing sequence (MLS) peptides. We showed that these multifunctional NDs not only distinguish between cancer cells and normal cells, and transport the loaded drugs across the plasma membrane of cancer cells, but also selectively deliver them to mitochondria and induce significant cytotoxicity and cell death compared with free Dox localized in lysosomes. Importantly, the cellular uptake of Dox was dramatically increased in a resistant model of MCF-7 cells, which contributed to the significant circumvention of P-glycoprotein-mediated drug resistance. Our work provides a novel method of designing nanodiamond-based carriers for targeted delivery and for circumventing drug resistance in doxorubicin-resistant human breast adenocarcinoma cancer cells.
Nanodiamond–gold nanoparticle (ND-AuNP) dimers constitute a potent tool for controlled thermal heating of biological systems on the nanoscale, by combining a local light-induced heat source with a ...sensitive local thermometer. Unfortunately, previous solution-based strategies to build ND-AuNP conjugates resulted in large nanoclusters or a broad population of multimers with limited separation efficiency. Here, we describe a new strategy to synthesize discrete ND-AuNP dimers via the synthesis of biotin-labeled DNA-AuNPs through thiol chemistry and its immobilization onto the magnetic bead (MB) surface, followed by reacting with streptavidin-labeled NDs. The dimers can be easily released from MB via a strand displacement reaction and separated magnetically. Our method is facile, convenient, and scalable, ensuring high-throughput formation of very stable dimer structures. This ligand-induced self-assembly approach enables the preparation of a wide variety of dimers of designated sizes and compositions, thus opening up the possibility that they can be deployed in many biological actuation and sensing applications.
We have demonstrated that the subcellular targeting properties of the indole-based cyanines can be tuned by the functional substituent attached onto the indole moiety in which the first example of a ...highly RNA-selective and two-photon active fluorescent light-up probe for high contrast and brightness TPEF images of rRNA in the nucleolus of live cells has been developed. It is important to find that this cyanine binds much stronger toward RNA than DNA in a buffer solution as well as selectively stains and targets to rRNA in the nucleolus. Remarkably, the TPEF brightness (Φσmax) is dramatically increased with 11-fold enhancement in the presence of rRNA, leading to the record high Φσmax of 228 GM for RNA. This probe not only shows good biocompatibility and superior photostability but also offers general applicability to various live cell lines including HeLa, HepG2, MCF-7, and KB cells and excellent counterstaining compatibility with commercially available DNA or protein trackers.
We demonstrate the use of two different wavelength ranges of excitation light as inputs to remotely trigger the responses of the self‐assembled DNA devices (D‐OR). As an important feature of this ...device, the dependence of the readout fluorescent signals on the two external inputs, UV excitation for 1 min and/or near infrared irradiation (NIR) at 800 nm fs laser pulses, can mimic function of signal communication in OR logic gates. Their operations could be reset easily to its initial state. Furthermore, these DNA devices exhibit efficient cellular uptake, low cytotoxicity, and high bio‐stability in different cell lines. They are considered as the first example of a photo‐responsive DNA logic gate system, as well as a biocompatible, multi‐wavelength excited system in response to UV and NIR. This is an important step to explore the concept of photo‐responsive DNA‐based systems as versatile tools in DNA computing, display devices, optical communication, and biology.
Light logic: A four‐part, fluorophore‐modified DNA device is designed to operate as an OR logic gate in response to two excitation wavelengths. This device could be reset with excess oligonucleotides, and was shown to be taken up by cultured mammalian cells.
The first example of mitochondrial delivery of the anticancer drug doxorubicin (Dox) is presented by lipid‐functionalized DNA nanocages (LNCs). Dox localized in mitochondria induces significant ...cytotoxicity and cellular apoptosis in MCF‐7 compared with Dox localized in lysosomes. These results suggest that LNC has the potential to be an outstanding tool in the treatment of specific organelle‐related diseases such as cancers.
Delivery of the anticancer drug doxorubicin to mitochondria by lipid‐functionalized DNA nanocages (LNCs) is demonstrated for the first time. The results suggest outstanding potential for the use of LNCs as drug nanocarriers in treatments for organelle‐specific diseases.
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•DNA nanocage/Quantum Dot complexes are constructed using electrostatic adsorption.•The complexes are in an aggregation-free state.•The aggregation-free nature relates to the 3D rigid ...structure of the DNA nanocage.
Fabrication of DNA/Quantum Dot (QD) complexes making use of electrostatic adsorption forces has advantages of the cost-efficiency and simplicity. To obtain aggregation-free complexes, high molecular weight polymers or the purposefully designed ligands are commonly employed as a bridge between DNA and QDs, which limits their applications in practice. In this work, DNA/QDs complexes were obtained using electrostatic adsorption between cysteamine stabilized CdTe QDs and self-assembled DNA nanocages. Zeta potential, dynamic light scattering and gel electrophoresis measurements demonstrated their aggregation-free state, different from the cases where single-stranded and double-stranded DNAs were used. The appearance of aggregation-free complexes in the case of DNA nanocages was ascribed to their 3D rigid structure. Förster resonance energy transfer (FRET) was demonstrated for the complexes of Cy3 labeled DNA nanocages and QDs, pointing out on the close proximity of these building blocks.
A series of 5,6-bis(2-ethylhexyloxy)naphtho2,1-b:3,4- b'dithiophene and 4,7-bis(3-alkylthiophen-2-yl)-2,1,3-benzoc1,2,5 thiadiazole alternating copolymers, PNB-Cn, with different alkyl chains, ...varying from 8-carbon (C8, 2-ethylhexyl) to 16-carbon (C16, hexadecyl) chains attached onto thienyl moieties were designed and synthesized. The effect of the conjugated copolymer side chain on the photovoltaic and charge mobility properties of organic solar cells (OSCs) and polymer field-effect transistors (PFETs) was investigated. It is found that the short alkyl side chains on PNB-Cn copolymers are favourable for the efficient operation of bulk heterojunction (BHJ) OSCs, while the long alkyl side chains enhance the charge mobility of PFETs. As a result, the BHJ OSCs fabricated from the blend of PNB-C2,6 and PC sub(71)BM, using diiodooctane as a solvent additive, yielded a power conversion efficiency of 4.8% and the solution-processed bottom gate bottom contact type PFETs fabricated from PNB-C16 exhibited a hole mobility of 3.4 10 super(-2) cm super(2) V super(-1) s super(-1) with an on/off current ratio of 10 super(6). Our results suggest that copolymers constructed from 5,6-bis(2-ethylhexyloxy)naphtho2,1-b:3,4- b'dithiophene and 4,7-bis(3-alkylthiophen-2-yl)-2,1,3-benzoc1,2,5 -thiadiazole are very stable, and solution-processable organic semiconductors for application in organic electronics.
Peptide‐functionalized DNA nano‐objects selectively target mitochondria and the nucleus by means of nanoneedle‐assisted delivery. This technology preserves the cell viability and structural integrity ...of nanostructures and assists the nano‐objects in escaping degradation by endocytosis. This method opens up a new avenue for further in vitro studies of intracellular behaviors of DNA assemblies and their interactions in specific organelles.
The development of biocompatible drug delivery vehicles for cancer therapy in the brain remains a big challenge. In this study, we designed self-assembled DNA nanocages functionalized with or without ...blood–brain barrier (BBB)-targeting ligands, d and we investigated their penetration across the BBB. Our DNA nanocages were not cytotoxic and they were substantially taken up in brain capillary endothelial cells and Uppsala 87 malignant glioma (U-87 MG) cells. We found that ligand modification is not essential for this DNA system as the ligand-free DNA nanocages (LF-NCs) could still cross the BBB by endocytosis inin vitro and in vivo models. Our spherical DNA nanocages were more permeable across the BBB compared with tubular DNA nanotubes. Remarkably, in vivo studies revealed that DNA nanocages could carry anticancer drugs across the BBB and inhibit the tumor growth in a U-87 MG xenograft mouse model. This is the first example showing the potential of DNA nanocages as innovative delivery vehicles to the brain for cancer therapy. Unlike other delivery systems, our work suggest that a DNA nanocage-based platform provides a safe and cost-effective tool for targeted delivery to the brain and therapy for brain tumors.
Short circulation lifetime, poor blood-brain barrier (BBB) permeability and low targeting specificity limit nanovehicles from crossing the vascular barrier and reaching the tumor site. Consequently, ...the precise diagnosis of malignant brain tumors remains a great challenge. This study demonstrates the imaging of photostable biopolymer-coated nanodiamonds (NDs) with tumor targeting properties inside the brain. NDs are labeled with PEGylated denatured bovine serum albumin (BSA) and tumor vasculature targeting tripeptides RGD. The modified NDs show high colloidal stability in different buffer systems. Moreover, it is found that discrete dcBSA-PEG-NDs cross the
in vitro
BBB model more effectively than aggregated NDs. Importantly, compared with the non-targeting NDs, RGD-dcBSA-PEG-NDs can selectively target the tumor site in U-87 MG bearing mice after systemic injection. Overall, this discrete ND system enables efficacious brain tumor visualization with minimal toxicity to other major organs, and is worthy of further investigation into the applications as a unique platform for noninvasive theragnostics and/or thermometry at different stages of human diseases in the brain.
A protein-derived nanodiamond-based nanoprobe with targeting properties is established for brain tumor imaging.
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