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A novel multifunctional drug‐delivery platform is developed based on cholesteryl succinyl silane (CSS) nanomicelles loaded with doxorubicin, Fe3O4 magnetic nanoparticles, and gold nanoshells (CDF‐Au‐shell nanomicelles) to combine magnetic resonance (MR) imaging, magnetic‐targeted drug delivery, light‐triggered drug release, and photothermal therapy. The nanomicelles show improved drug‐encapsulation efficiency and loading level, and a good response to magnetic fields, even after the formation of the gold nanoshell. An enhancement for T2‐weighted MR imaging is observed for the CDF‐Au‐shell nanomicelles. These nanomicelles display surface plasmon absorbance in the near‐infrared (NIR) region, thus exhibiting an NIR (808 nm)‐induced temperature elevation and an NIR light‐triggered and stepwise release behavior of doxorubicin due to the unique characteristics of the CSS nanomicelles. Photothermal cytotoxicity in vitro confirms that the CDF‐Au‐shell nanomicelles cause cell death through photothermal effects only under NIR laser irradiation. Cancer cells incubated with CDF‐Au‐shell nanomicelles show a significant decrease in cell viability only in the presence of both NIR irradiation and a magnetic field, which is attributed to the synergetic effects of the magnetic‐field‐guided drug delivery and the photothermal therapy. Therefore, such multicomponent nanomicelles can be developed as a smart and promising nanosystem that integrates multiple capabilities for effective cancer diagnosis and therapy.  相似文献   
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聚乙二醇/聚己内酯两亲性三嵌段共聚物纳米胶束   总被引:2,自引:0,他引:2  
研究了制备聚乙二醇-b-聚己内酯-b-聚乙二醇两亲性三嵌段共聚物(PECL)纳米胶束的各种影响因素,发现PECL纳米胶束的粒径受制备方法的影响较大,且随着PECL的相对分子质量和混合溶剂中二氯甲烷用量的增大而增大。PECL的临界聚集浓度小于4×10-6mol/L,随着共聚物相对分子质量的增大而减小,纳米分散液的临界聚沉浓度随着PECL中PCL相对分子质量的增加而减小,分散液稳定性下降。  相似文献   
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Poly[L-lysine-co-N,N-bis(acryloyl) cystamine-co-dodecylamine] nanomicelles (NMs) were synthesized through Michael addition terpolymerization in one pot. The NMs showed spheric morphology and uniform size distributions. The NMs had excellent nonspecific protein adsorption ability at pH 7.4. Doxorubicin (DOX) was loaded in the NMs for the investigation of controlled release. The drug delivery results showed that the DOX-loaded NMs displayed apparent pH and reduction sensitivities in response to the environment of tumor cells due to the existence of carboxyl groups, amino groups, and disulfide bonds in the NMs. The NMs were biocompatible, biodegradable, and could be potentially used as drug vehicles in controlled release.  相似文献   
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Self‐assembly is a fundamental concept and a powerful approach in molecular science. However, creating functional materials with the desired properties through self‐assembly remains challenging. In this work, through a combination of experimental and computational approaches, the self‐assembly of small amphiphilic dendrons into nanosized supramolecular dendrimer micelles with a degree of structural definition similar to traditional covalent high‐generation dendrimers is reported. It is demonstrated that, with the optimal balance of hydrophobicity and hydrophilicity, one of the self‐assembled nanomicellar systems, totally devoid of toxic side effects, is able to deliver small interfering RNA and achieve effective gene silencing both in cells – including the highly refractory human hematopoietic CD34+ stem cells – and in vivo, thus paving the way for future biomedical implementation. This work presents a case study of the concept of generating functional supramolecular dendrimers via self‐assembly. The ability of carefully designed and gauged building blocks to assemble into supramolecular structures opens new perspectives on the design of self‐assembling nanosystems for complex and functional applications.  相似文献   
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The aim of this study was to develop hydroxypropyl methyl cellulose (HPMC)/chitosan gel containing polymeric micelles loaded with simvastatin (Sim) and evaluates its wound healing properties in rats. An irregular full factorial design was employed to evaluate the effects of various formulation variables including polymer/drug ratio, hydration temperature, hydration time, and organic solvent type on the physicochemical characteristics of pluronic F127-cholesterol nanomicelles prepared using the film hydration method. Among single studied factors, solvent type had the most impact on the amount of drug loading and zeta potential. Particle size and release efficiency was more affected by hydration temperature. The optimized formulation suggested by desirability of 93.5% was prepared using 1?mg of Sim, 10?mg of copolymer, dichloromethane as the organic solvent, hydration time of 45?min and hydration temperature of 25?°C. The release of the drug from nanomicelles was found to be biphasic and showed a rapid release in the first stage followed by a sustained release for 96?h. The gel-contained nanomicelles exhibited pseudo-plastic flow and more sustained drug release profile compared to nanomicelles. In excision wound model on normal rats, the wound closure of the group treated by Sim loaded micelles-gel was superior to other groups. Taken together, Sim loaded micelles-gel may represent a novel topical formulation for wound healing.  相似文献   
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Recently, interdisciplinary research in cancer diagnosis and therapy has evolved to the point where nanotechnology particularly polymeric nanodelivery systems are utilized for theragnostic applications. Nanoscale are being trialed for specific targeted delivery of drugs, micelles, antibody, DNA, protein, etc. to cancer sites to improve the therapeutic efficacy due to improved distribution specificity, increased internalization, and intracellular drug delivery that minimize the side effects. Polymeric micelles have been subjected to extensive studies in the field of drug delivery, functioning as drug solubilizers and carriers. More recently, a micelle constructed as a hybrid from hydrophilic oligonucleotide and hydrophobic polymer has drawn close attention. Mostly used micelles are synthesized with polymer and have several physical properties, including molecular weight and copolymer block composition, which can be tailored to alter the vesicle structure. In this review, we focused on the different polymeric nanodelivery systems is association with different type of cancer therapeutics such as micelles, drug, aptamer, DNA, recombinant protein, miRNA, siRNA, small inhibitors, gene, antibody, proteins and some conjugating molecules that involved in cancer therapy have been discussed.  相似文献   
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The development of a minimally invasive therapy for local targeting of adipose tissues could represent an attractive approach for treating obesity. Here, the development and successful application of a nanomedicine that uses α-lactalbumin (α-lac) nanomicelles (M) to encapsulate the known anti-obesity agent capsaicin (Cap), which is delivered directly to adipose tissue via a microneedle patch (MP), is reported. Testing with a 3T3-L1 adipocyte model shows that M (Cap) reduces lipid droplet content by regulating adipogenesis and improving mitochondrial biogenesis. The MP enables efficient M (Cap) penetration into abdominal subcutaneous adipose tissue, and M (Cap) can be endocytosed by white adipocytes. Experiments using a high fat diet-induced obese mice model shows that MP-delivered M (Cap) confers dramatic weight loss and adipose tissue browning, and follow-up mechanistic investigations indicate (among other impacts) activated energy metabolism, increased mitochondrial biogenesis, and the induction of well-known adipocyte browning markers. The study supports that MP-M (Cap) treatment, which could be developed as a self-administered therapy based on skin attachment for around 30 min, has a promising future as a non-invasive approach for treating obesity.  相似文献   
9.
Understanding the direct interaction of nanostructures per se with biological systems is important for biomedical applications. However, whether nanostructures regulate biological systems by targeting specific cellular proteins remains largely unknown. In the present work, self-assembling nanomicelles are constructed using small-molecule oleanolic acid (OA) as a molecular template. Unexpectedly, without modifications by functional ligands, OA nanomicelles significantly activate cellular proteasome function by directly binding to 20S proteasome subunit alpha 6 (PSMA6). Mechanism study reveals that OA nanomicelles interact with PSMA6 to dynamically modulate its N-terminal domain conformation change, thereby controlling the entry of proteins into 20S proteasome. Subsequently, OA nanomicelles accelerate the degradation of several crucial proteins, thus potently driving cancer cell pyroptosis. For translational medicine, OA nanomicelles exhibit a significant anticancer potential in tumor-bearing mouse models and stimulate immune cell infiltration. Collectively, this proof-of-concept study advances the mechanical understanding of nanostructure-guided biological effects via their inherent capacity to activate proteasome.  相似文献   
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