Small‐sized cationic miRi (microRNA‐21 inhibitor)‐PCNPs (low molecular weight chitosan (LMWC)‐modified polylactide‐co‐glycoside (PLGA) nanoparticles (PLNPs)) with special kidney‐targeting and high‐efficiency antifibrosis treatment are fabricated through coupling miRi, PLGA, and LMWC. In the miRi‐PCNPs, easily degraded miRi is encapsulated in PCNPs and thus prevented from degradation by nuclease. Cytotoxicity, immunotoxicity, and systemic toxicity assays and in vitro and ex vivo fluorescence imaging suggest that PCNPs possess excellent biocompatibility, higher cellular uptake efficiency, and selective kidney‐targeting capacity. Western blotting, pathological staining, and real‐time polymerase chain reaction analyses show that the therapeutic effect of miRi‐PCNPs on kidney fibrosis is much higher than that of miRi, which is mainly through suppressing transforming growth factor beta‐1/drosophila mothers against decapentaplegic protein 3 (TGF‐β1/Smad3) and extracellular signal–regulated kinases/mitogen‐activated protein kinase signaling pathway by inhibiting the expression of microRNA‐21. For example, the tubule damage index and tubulointerstitial fibrosis area in the miRi‐PCNPs group are ≈2.5‐fold lower than those in the saline and bare miRi groups. The miRi‐PCNPs with special kidney‐targeting and high‐efficiency antifibrosis treatment may represent a promising strategy for designing and developing a therapeutic treatment for kidney fibrosis.
A fluorescence turn-on
system for highly efficient and prolonged
tumor imaging has been established by a Co2+-induced coordination
self-assembly strategy, in which luminescent glutathione (GSH)-modified
gold nanoparticles (LGAuNPs) are assembled into LGAuNPs assemblies
(LGAuNPs-Co) through a coordination bond between an unoccupied orbit
of Co2+ and lone pair electrons of GSH on the surface of
LGAuNPs. The LGAuNPs-Co is sensitive to microenvironment pH, and its
quenched luminescence will be turned on in tumor tissues (acidic microenvironment),
which behaves as a fluorescence turn-on system for passive tumor imaging.
The fluorescence turn-on system combines advantages of the enhanced
permeability and retention (EPR) effect of NPs and pH-induced fluorescence
turn-on property at the tumor site, which results in a larger fluorescence
intensity (FI) difference between normal and tumor tissues as compared
with that of luminescent Au NPs (LAuNPs, only with the EPR effect)
(∼12-fold). Such a large FI difference results in that LGAuNPs-Co
has rapid (∼1.6 h), persistent (∼24 h p.i.), and highly
efficient tumor targeting capability in comparison with LGAuNPs. Moreover,
the LGAuNPs-Co also has much longer tumor retention, faster renal
clearance, and lower reticuloendothelial system (RES) uptake than
LGAuNPs. Therefore, the fluorescence turn-on system is very promising
for cancer diagnosis and therapy.
A Stimuli-responsive drug release nanoassemblies (GLAuNPs-Co) had selective kidney targeting, pH-triggered and drug-releasable abilities for renal fibrosis.
Au nanoparticles (NPs) have important applications in bioimaging, clinical diagnosis and even therapy due to its water-solubility, easy modification and drug-loaded capability, however, easy aggregation of Au NPs in normal saline and serum greatly limits its applications. In this work, highly stabilized core-satellite Au nanoassemblies (CSAuNAs) were constructed by a hierarchical DNA-directed self-assembly strategy, in which satellite Au NPs number could be effectively tuned through varying the ratios of core-AuNPs-ssDNA and satellite-AuNPs-ssDNAc. It was especially interesting that PEG-functionalized CSAuNAs (PEG-CSAuNAs) could not only bear saline solution but also resist the enzymatic degradation in fetal calf serum. Moreover, cell targeting and imaging indicated that the PEG-CSAuNAs had promising biotargeting and bioimaging capability. Finally, fluorescence imaging in vivo revealed that PEG-CSAuNAs modified with N-acetylation chitosan (CSNA) could be selectively accumulate in the kidneys with satisfactory renal retention capability. Therefore, the highly stabilized PEG-CSAuNAs open a new avenue for its applications in vivo.
In this work, a hierarchical DNA–directed self–assembly strategy to construct structure–controlled Au nanoassemblies (NAs) has been demonstrated by conjugating Au nanoparticles (NPs) with internal–modified dithiol single-strand DNA (ssDNA) (Au–B–A or A–B–Au–B–A). It is found that the dithiol–ssDNA–modified Au NPs and molecule quantity of thiol–modified ssDNA grafted to Au NPs play critical roles in the assembly of geometrically controlled Au NAs. Through matching Au–DNA self–assembly units, geometrical structures of the Au NAs can be tailored from one–dimensional (1D) to quasi–2D and 2D. Au–B–A conjugates readily give 1D and quasi–2D Au NAs while 2D Au NAs can be formed by A–B–Au–B–A building blocks. Surface-enhanced Raman scattering (SERS) measurements and 3D finite–difference time domain (3D-FDTD) calculation results indicate that the geometrically controllable Au NAs have regular and linearly “hot spots”–number–depended SERS properties. For a certain number of NPs, the number of “hot spots” and accordingly enhancement factor of Au NAs can be quantitatively evaluated, which open a new avenue for quantitative analysis based on SERS technique.
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