We suggest that the FPS may provide a new treatment algorithm in some cases with acne scars and enlarged pores. Considering the lack of placebo-controlled, split-face design of our study, optimized, prospective studies should be conducted to fully assess the efficacy of FPS with dynamic operating mode.
Many aptamers have been evaluated for their ability as drug delivery vehicles to target ligands, and a variety of small interfering RNAs (siRNAs) have been tested for their anti-cancer properties. However, since these two types of molecules have similar physicochemical properties, it has so far been difficult to formulate siRNA-encapsulating carriers guided by aptamers. Here, we propose aptamer-coupled lipid nanocarriers encapsulating quantum dots (QDs) and siRNAs for theragnosis of triple-negative breast cancer (TNBC).
Methods:
Hydrophobic QDs were effectively incorporated into lipid bilayers, and then therapeutic siRNAs were complexed with QD-lipid nanocarriers (QLs). Finally, anti-EGFR aptamer-lipid conjugates were inserted into the QLs for TNBC targeting (aptamo-QLs). TNBC-targeting aptamo-QLs were directly compared to anti-EGFR antibody-coupled immuno-QLs. The
in vitro
delivery of therapeutic siRNAs and QDs to target cells was assessed by flow cytometry and confocal microscopy. The
in vivo
targeting of siRNAs to tumors and their therapeutic efficacy were evaluated in mice carrying MDA-MB-231 tumors.
Results:
Both types of EGFR-targeting QLs showed enhanced delivery to target cancer cells, resulting in more effective gene silencing and enhanced tumor imaging compared to non-targeting control QLs. Moreover, combinatorial therapy with Bcl-2 and PKC-ι siRNAs loaded into the anti-EGFR QLs was remarkably effective in inhibiting tumor growth and metastasis.
Conclusion:
In general, the aptamo-QLs showed competitive
in vivo
delivery and therapeutic efficacy compared to immuno-QLs under the same experimental conditions. Our results show that the anti-EGFR aptamer-guided lipid carriers may be a potential theranostic delivery vehicle for RNA interference and fluorescence imaging of TNBCs.
Co-application of fluorescent quantum dot nanocrystals and therapeutics has recently become a promising theranostic methodology for cancer treatment. We developed a tumor-targeted lipid nanocarrier that demonstrates notable efficacy in gene delivery as well as tumor bio-imaging. Coupling of aptamer molecules against the EGF receptor (EGFR) to the distal termini of lipid nanoparticles provided the carrier with tumor-specific recognition capability. The cationic lipid component, referred to as O,O’-dimyristyl-N-lysyl glutamate (DMKE), was able to effectively complex with anionic small-interfering RNA (siRNA). The hydrophobic quantum dots (Q-dots) were effectively incorporated in hydrophobic lipid bilayers at an appropriate Q-dot to lipid ratio. In this study, we optimized the liposomal formula of aptamer-conjugated liposomes containing Q-dots and siRNA molecules (Apt-QLs). The anti-EGFR Apt-QLs exhibited remarkable EGFR-dependent siRNA delivery as well as fluorescence imaging, which were analyzed in cultured cancer cells and tumor xenografts in mice. These results imply that the formulation of Apt-QLs could be widely utilized as a carrier for tumor-directed gene delivery and bio-imaging.
The development of reliable synthetic routes to polymer nanomaterials with well-defined size and morphology is a critical research topic in contemporary materials science. The ability to generate nanometer-sized polymer materials can offer unprecedented, interesting insights into the physical and chemical properties of the corresponding materials. In addition, control over shape and geometry of polymer nanoparticles affords versatile polymer nanostructures, encompassing nanospheres, core-shell nanoparticles, hollow nanoparticles, nanorods/ fibers, nanotubes, and nanoporous materials. This review summarizes a diverse range of synthetic methods (broadly, hard template synthesis, soft template synthesis, and template-free synthesis) for fabricating polymer nanomaterials. The basic concepts and significant issues with respect to the synthetic strategies and tools are briefly introduced, and the examples of some of the outstanding research are highlighted. Our aim is to present a comprehensive review of research activities that concentrate on fabrication of various kinds of polymer nanoparticles.
Incidence of HPV-related oropharyngeal SCC in Korea is similar to U.S.-European data. HPV presence correlates with improved survival. Expression ratios of G1 markers may predict survival of oropharyngeal SCCs better than each marker alone.
For electrical impedance tomography (EIT), most practical reconstruction methods are based on linearizing the underlying non-linear inverse problem. Recently, it has been shown that the linearized problem still contains the exact shape information. However, the stable reconstruction of shape information from measurements of finite accuracy on a limited number of electrodes remains a challenge.In this work we propose to regularize the standard linearized reconstruction method (LM) for EIT using a non-iterative shape reconstruction method (the factorization method). Our main tool is a discrete sensitivity-based variant of the factorization method (herein called S-FM) which allows us to formulate and combine both methods in terms of the sensitivity matrix. We give a heuristic motivation for this new method and show numerical examples that indicate its good performance in the localization of anomalies and the alleviation of ringing artifacts.
SUMMARYInterleukin-5 (IL-5) and eotaxin are the most important cytokines/chemokines responsible for regulating eosinophil locomotion and are known to play a co-operative role in the selective recruitment of eosinophils to inflamed tissues. Following exposure to chemoattractants, eosinophils undergo a series of events, including reorganization of actin filaments and subsequent rapid shape changes, culminating in chemotaxis. In this study we examined the signalling pathways for eosinophil shape change regulated by eotaxin and IL-5, primarily using a gated autofluorescence/forward-scatter assay. Eotaxin and IL-5 were able to elicit shape change with peaks at 10 and 60 min, respectively, and IL-5 triggered the shape change more efficiently than eotaxin. The pharmacological inhibitors of mitogen-activated protein kinase (MAP kinase) and p38 blocked both eotaxin-and IL-5-induced eosinophil shape change in a dose-dependent manner. In addition, depletion of intracellular Ca 2þ and inhibition of protein kinase A (PKA) strongly reduced eosinophil shape change. In contrast, even when used at high concentrations, protein tyrosine kinase (PTK) inhibitors caused only a slight reduction in the ability to change shape. However, treatment with protein kinase C (PKC) inhibitors, such as GF109203X and staurosporine, resulted in a striking inhibition of eosinophil shape change by IL-5, but not eotaxin. Data from the inhibition of activation and chemotaxis of the extracellular signal-regulated kinases (ERK1/2) by the PKC inhibitors were also consistent with findings from the experiments on shape change. Collectively, two eosinophilselective cytokines/chemokines probably regulate eosinophil shape change via a largely overlapping signalling pathway, with involvement of PKC restricted to the IL-5 signal alone.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.