In this work, a paramagnetic nanofibrous composite film was fabricated with poly lactide, hydroxyapatite and γ-Fe(2)0(3) nanoparticles using the electrospinning technique. The composite film significantly enhanced the proliferation, differentiation and ECM secretion of the osteoblast cells under a static magnetic field, which offers promising application potentials in bone tissue engineering and bone regeneration therapy.
Catalytic deoxyribozyme has great potential for gene regulation, but the poor efficiency of the cleavage of mRNA and the lack of versatile DNAzyme vehicles remain big challenges for potent gene therapy. By the rational designing of a diverse vehicle of polydopamine-Mn 2+ nanoparticles (MnPDA), we demonstrate that MnPDA has integrated functions as an effective DNAzyme delivery vector, a self-generation source of DNAzyme cofactor for catalytic mRNA cleavage, and an inherent therapeutic photothermal agent as well as contrast agent for photoacoustic and magnetic resonance imaging. Specifically, the DNAzyme-MnPDA nanosystem protects catalytic deoxyribozyme from degradation and enhances cellular uptake efficiency. In the presence of intracellular glutathione, the nanoparticles are able to in situ generate free Mn 2+ as a cofactor of DNAzyme to effectively trigger the catalytic cleavage of mRNA for gene silencing. In addition, the nanosystem shows high photothermal conversion efficiency and excellent stability against photothermal processing and degradation in complex environments. Unlike previous DNAzyme delivery vehicles, this vehicle exhibits diverse functionalities for potent gene regulation, allowing multimodal imaging-guided synergetic gene regulation and photothermal therapy both in vitro and in vivo.
The extreme complexity and heterogeneity of fatal tumors requires the development of combination phototherapy considering the limited therapeutic efficiency of conventional monomodal photodynamic therapy (PDT) or photothermal therapy (PTT).
Photodynamic therapy( PDT) has extraordinary promise for the treatment of many cancers.H owever,i ts clinical progress is impaired by the intrinsic hypoxic tumor microenvironment that limits PDT efficacy and the safety concern associated with biological specificity of photosensitizers or vehicles.N ow it is demonstrated that rationally designed DNAn anosponges can load and delivery photosensitizer effectively,t arget tumor precisely,a nd relieve hypoxia-associated resistance remarkably to enhance the efficacy of PDT.S pecifically,t he approach exhibits af acile assembly process,p rovides programmable and versatile nanocarriers, and enables robust in vitro and in vivo anti-cancer efficacy with excellent biosafety.T hese findings represent ap ractical and safe approachb yd esigner DNAn anoassemblies to combat cancer effectively and suggest ap owerful strategy for broad biomedical application of PDT.
Programmable metal–organic frameworks were prepared as efficient delivery vehicles for targeted and stimuli-responsive release of multi-therapeutics with excellent antitumor activity.
Carbon nanotubes have been shown to have the ability to transport therapeutic and detective reagents into cells. However, the rapid advances in new carbon nanotube-based materials and technologies have raised concerns about their safety. Such concerns require a fundamental understanding of the toxicological properties of carbon nanotubes. In particular, the use of carbon nanotubes as drug or probe delivery platforms may depend on the prevention of stimulatory side-effects to the immune system. In this study, we investigated the immunological properties of oxidized water dispersible multi-walled carbon nanotubes (MWCNTs) in healthy BALB/c mice. We injected the MWCNTs subcutaneously, and the immune responses of the mice were monitored over time. We show that the MWCNTs induce complement activation and the production of pro-inflammatory cytokines early after injection of the mice, and that the levels of complement and cytokines return to normal levels over time. With the exception of the lymph nodes, there was no obvious accumulation of MWCNTs observed in the liver, spleen, kidney, or heart. In addition, we did not observe injury in the organs or lymph nodes. Our results indicate that local, subcutaneous administration of MWCNTs induces obvious short-term immunological reactions, which can be eliminated over time.
Biomedical application potentials of carbon nanotubes-based materials have been investigated intensively in recent years; however, characterization and metrology are still facing great technical challenges when the materials are intended to be used as carriers for therapeutics in aqueous solutions. Systematic characterization on the dispersing carbon nanotubes is urgently required and therefore of significance. In this paper multiwalled carbon nanotubes (MWCNTs) with different average lengths or with different oxidation degrees were dispersed in water and characterized systematically by applying UV spectroscopy, SEM, DLS, TGA, XPS, and FTIR. In particular, the characteristic absorption of the carbon nanotubes was analyzed using resolution-fitting technique to establish relations of wavelength and absorption intensity to the size distribution and surface chemistry. Results indicated that the absorption spectra of MWCNTs could reflect the variation of surface chemistry and length distribution of carbon nanotubes dispersed in water by combining with the other measurements. A vascular endothelium cell line was taken as a model to figure out association between physicochemical features and cytotoxicity of the carbon nanotubes. It was showed that the multiwalled carbon nanotubes with different oxidation degrees and similar length distribution exhibited different interaction files to the cells proliferation in a manner of time dependence and concentration dependence.
Small interfering
RNA (siRNA)-induced gene therapy has been recognized
as a promising avenue for effective cancer treatment, while easy enzymatic
degradation, poor transfection efficiency, nonspecific biodistribution,
and uncontrolled release hinder its extensive clinical applications.
Zeolitic imidazolate frameworks-8 (ZIF-8) have emerged as promising
drug carriers without an in-depth exploration in programmable siRNA
delivery. Herein, we report a multifunctional PDAs-ZIF-8 (PZ) nanoplatform
for delivering siRNA with combined photothermal therapy (PTT) and
gene therapy (GT) via the noninvasive guidance of
photoacoustic (PA)/near-infrared (IR) dual-modal imaging. The ingenious
PZ nanocarriers mediated the tumor-specific accumulation of therapeutic
siRNA without undesired degradation and preleakage. The pH-responsive
ZIF-8 decomposed in an acidic tumor microenvironment that was accompanied
by the release of siRNA payloads for cleaving target mRNA in gene
silencing therapy. Meanwhile, the polydopamine nanoparticles (PDAs)
could simultaneously serve as a powerful noninvasive PA/IR imaging
contrast agent and versatile photothermal agent for diagnosis-guided
photogenetherapy. The systematic in vitro and in vivo experimental explorations demonstrated that our
PDAs-siRNA-ZIF-8 (PSZ) could greatly enhance the therapeutic efficiency
as compared with the corresponding PTT or GT monotherapy. This work
holds great potential to advance the development of more intelligent
diagnosis and therapeutic strategies, thus supplying promising smart
nanomedicines in the near future.
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