4 research outputs found
Reinforced Self-Assembly of Donor–Acceptor π‑Conjugated Molecules to DNA Templates by Dipole–Dipole Interactions Together with Complementary Hydrogen Bonding Interactions for Biomimetics
One of the most important criteria for the successful
DNA-templated polymerization to generate fully synthetic biomimetic
polymers is to design the complementary structural monomers, which
assemble to the templates strongly and precisely before carrying polymerization.
In this study, water-soluble, laterally thymine-substituted donor–acceptor
Ď€-conjugated molecules were designed and synthesized to self-assemble
with complementary oligoadenines templates, dA<sub>20</sub> and dA<sub>40</sub>, into stable and tubular assemblies through noncovalent
interactions including π–π stacking, dipole–dipole
interactions, and the complementary adenine-thymine (A-T) hydrogen-bonding.
UV–vis, fluorescence, circular dichroism (CD), atomic force
microscopy (AFM), and transmission electron microscopy (TEM) techniques
were used to investigate the formation of highly robust nanofibrous
structures. Our results have demonstrated for the first time that
the dipole–dipole interactions are stronger and useful to reinforce
the assembly of donor–acceptor π-conjugated molecules
to DNA templates and the formation of the stable and robust supramolecular
nanofibrous complexes together with the complementary hydrogen bonding
interactions. This provides an initial step toward DNA-templated polymerization
to create fully synthetic DNA-mimetic polymers for biotechnological
applications. This study also presents an opportunity to precisely
position donor–acceptor type molecules in a controlled manner
and tailor-make advanced materials for various biotechnological applications
Cancer-Cell-Specific Mitochondria-Targeted Drug Delivery by Dual-Ligand-Functionalized Nanodiamonds Circumvent Drug Resistance
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
Dual-Function, Cationic, Peptide-Coated Nanodiamond Systems: Facilitating Nuclear-Targeting Delivery for Enhanced Gene Therapy Applications
Nuclear-targeting therapy is considered
to be a promising strategy
of disease treatment. So far, developing biocompatible and nucleus-permeable
delivery systems remains a great challenge. Here, we report a nuclear-targeted
delivery platform based on 30 nm nanodiamonds (NDs) which were coated
with dual-function, cationic peptides consisting of the human immounodeficiency
virus TAT protein and a nuclear localization signal (NLS) peptide
in aqueous media. As compared to uncoated NDs, cationic peptide-functionalized
NDs were confirmed as a small, safe, and efficient carrier which not
only facilitates the enhanced cellular uptake and delivery of loaded
cargos to the nucleus in a number of cell lines but also shows their
advantages of low cytotoxicity and high affinity to antisense oligonucleotides.
This peptide-based modification strategy does not contribute greatly
to the size of the ND which is important in its use in constructing
nuclear targeting vehicles. Compared with traditional gene silencing
in cytoplasm, our findings suggest that the nuclear localization effect
of ANA4625-TAT-NLS-NDs enhances the therapeutic efficacy of antisense
oligonucleotide ANA4625 as evidenced by suppression of the targets <i>bcl-2</i> and <i>bcl-xL</i> pre-mRNA/protein expressions
and the induction of cell apoptosis. The studies have also revealed
that NDs can be used to mediate sustained release of antisense agents
with preserved therapeutic activity as inhibition of target mRNA expression
in a time- and dose-dependent manner. This work not only demonstrates
the design of a new nanodiamond-based platform for nuclear targeting
but also provides significant insights on nuclear-targeting delivery
of cell membrane impermeable therapeutic agents for enhanced disease
treatment
Enzyme-Free Amplification by Nano Sticky Balls for Visual Detection of ssDNA/RNA Oligonucleotides
Visual detection of nucleic acids
provides simple and rapid screening for infectious diseases or environmental
pathogens. However, sensitivity is the current bottleneck, which may
require enzymatic amplification for targets in low abundance and make
them incompatible with detection at resource-limited sites. Here we
report an enzyme-free amplification that provides a sensitive visual
detection of ssDNA/RNA oligonucleotides on the basis of nano “sticky
balls”. When target oligonucleotides are present, magnetic
microparticles (MMPs) and gold nanoparticles (AuNPs) were linked together,
allowing the collection of AuNPs after magnetic attraction. Subsequently,
the collected AuNPs, which carry many oligonucleotides, were used
as the sticky balls to link a second pair of MMPs and polymer microparticles
(PMPs). Thus, because the magnetic field can attract the MMPs as well
as the linked PMPs to the sidewall, the reduction of suspended PMPs
yields a change of light transmission visible by the naked eye. Our
results demonstrate that the limit of detection is 10 amol for ssDNAs
(228 fM in 45 ÎĽL) and 75 amol for ssRNAs (1.67 pM in 45 ÎĽL).
This method is also compatible with the serum environment and detection
of a microRNA, miR-155, derived from human breast cancer cells. With
significantly improved sensitivity for visual detection, it provides
great potential for point-of-care applications at resource-limited
sites