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51.
The Application of Stimuli‐Responsive VEGF‐ and ATP‐Aptamer‐Based Microcapsules for the Controlled Release of an Anticancer Drug,and the Selective Targeted Cytotoxicity toward Cancer Cells 下载免费PDF全文
Wei‐Ching Liao Yang Sung Sohn Marianna Riutin Alessandro Cecconello Wolfgang J. Parak Rachel Nechushtai Itamar Willner 《Advanced functional materials》2016,26(24):4262-4273
The synthesis of microcapsules consisting of DNA shells crosslinked by anti‐VEGF (vascular epithelial growth factor) or anti‐ATP (adenosine triphosphate) aptamers and loaded with tetramethylrhodamine‐modified dextran, TMR‐D, and Texas Red‐modified dextran, TR‐D, respectively, as fluorescence labels acting as models for drug loads, is described. The aptamer‐functionalized microcapsules act as stimuli‐responsive carriers for the triggered release of the fluorescent labels in the presence of the overexpressed cancer cell biomarkers VEGF or ATP. The VEGF‐ and ATP‐responsive microcapsules are, also, loaded with the anticancer drug doxorubicin (DOX), in the form of DOX‐functionalized dextran, DOX‐D. The release of DOX‐D from the respective microcapsules proceeds in the presence of VEGF or ATP as triggers. Preliminary cell experiments reveal that the ATP‐responsive DOX‐D‐loaded microcapsules undergo effective endocytosis into MDA‐MB‐231 cancer cells. The ATP‐responsive DOX‐D‐loaded microcapsules incorporated into the MDA‐MB‐231 cancer cells reveal impressive cytotoxicity as compared to normal epithelial MCF‐10A breast cells (50% vs 0% cell death after 24 h, respectively). The cytotoxicity of the ATP‐responsive DOX‐D‐loaded microcapsules toward the cancer cells is attributed to the effective unlocking of the microcapsules by overexpressed ATP, and to the subsequent release of DOX from the dextran backbone under acidic conditions present in cancer cells (pH = 6.2). 相似文献
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采用水解法用TiO_2包覆上转换纳米粒子Na YF4:Yb,Tm@NaGdF4:Yb,然后修饰聚乙烯亚胺(PEI)和聚丙烯酸(PAA)并偶联叶酸(FA),制备了叶酸受体靶向纳米光敏剂(NaYF4∶Yb,Tm@NaGdF4∶Yb@TiO_2@PEIPAA-FA)。借助XRD和TEM表征NaYF4∶Yb,Tm@NaGdF4∶Yb@TiO_2的物相和形貌,FTIR和Zeta电位证实有机成分的成功修饰,并测试了产物的上转换发光光谱。结果表明:在980 nm近红外光(NIR)下,纳米光敏剂存在下的1,3-二苯基异苯并呋喃溶液吸收光谱的降低证明了单线态氧的产生。此外,纳米光敏剂可以载带阿霉素(DOX),最大载药率为50.8%,包封率为84.7%。载药后的纳米光敏剂中DOX释放对介质具有pH响应性,在NIR照射的酸性介质(pH=5.0)中12 h的累积缓释率为38.1%,远高于中性介质(pH=7.4)的10.4%。 相似文献
53.
A Novel Pseudo‐Protein‐Based Biodegradable Nanomicellar Platform for the Delivery of Anticancer Drugs 下载免费PDF全文
Amino acid‐based poly(ester amide)s are a new family of biodegradable polymers that exhibit “pseudo‐protein” characteristics and the structural varieties of poly(ester amide)s make them hold great potential in multiple biomedical applications. In this study, a lysine‐phenylalanine‐based pseudo‐protein is developed as the self‐assembled nanomicellar carrier for efficient delivery of doxorubicin. The lysine moieties from the pseudo‐protein provide available sites for further functionalization, and methylcoumarin is introduced for easy and photocontrollable crosslinking, to effectively improve the micellar stability in serum containing environment and against dilution. However, photocrosslinks do not bring in any barrier for the intracellular release of doxoubicin. Doxorubicin release is significantly accelerated by proteolytic enzyme, due to the biodegradability of pseudo‐protein micelles. In addition, pseudo‐protein delivery system exhibits unique interactions with HCT116 human colon cancer cells. Doxorubicin loaded in pseudo‐protein micelles colocalizes with mitochondria and endolysosomes, while free doxorubicin is distributed only in the nuclei. Doxorubicin‐loaded pseudo‐protein micelles stimulate increased level of intracellular reactive oxygen species and mitochondrial damage. Free doxorubicin induces conditional apoptosis in HCT116 cells between 0.5× 10?6 and 2 × 10?6 m , while DOX loaded in pseudo‐protein micelles induces apoptosis over a higher/broader concentration range (2 × 10?6–10 × 10?6 m ). 相似文献
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Nahid Poorgholy Bakhshali Massoumi Marjan Ghorbani 《Drug development and industrial pharmacy》2018,44(8):1254-1261
This article evaluates the anticancer drug delivery performances of two nanohydrogels composed of poly(N-isopropylacrylamide-co-itaconic anhydride) [P(NIPAAm-co-IA)], poly(ethylene glycol) (PEG), and Fe3O4 nanoparticles. For this purpose, the magnetite nanohydrogels (MNHGs) were loaded with doxorubicin hydrochloride (DOX) as a universal anticancer drug. The morphologies and magnetic properties of the DOX-loaded MNHGs were investigated using transmission electron microscopy (TEM) and vibrating–sample magnetometer (VSM), respectively. The sizes and zeta potentials (ξ) of the MNHGs and their corresponding DOX-loaded nanosystems were also investigated. The DOX-loaded MNHGs showed the highest drug release values at condition of 41?°C and pH 5.3. The drug-loaded MNHGs at physiological condition (pH 7.4 and 37?°C) exhibited negligible drug release values. In vitro cytotoxic effects of the DOX-loaded MNHGs were extensively evaluated through the assessing survival rate of HeLa cells using the MTT assay, and there in vitro cellular uptake into the mentioned cell line were examined using fluorescent microscopy and fluorescence-activated cell sorting (FACS) flow cytometry analyses. As the results, the DOX-loaded MNHG1 exhibited higher anticancer drug delivery performance in the terms of cytotoxic effect and in vitro cellular uptake. Thus, the developed MNHG1 can be considered as a promising de novo drug delivery system, in part due to its pH and thermal responsive drug release behavior as well as proper magnetite character toward targeted drug delivery. 相似文献
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Alessia Salzillo Angela Ragone Annamaria Spina Silvio Naviglio Luigi Sapio 《International journal of molecular sciences》2021,22(16)
Despite the recurring outbreak of resistance mechanisms and adverse reactions, doxorubicin (Doxo) still remains the standard-of-care for several cancers, including osteosarcoma (OS). As an appealing source of phytochemical compounds, naturally occurring molecules have extensively been reported to overcome Doxo limitations in preclinical models. Unlike other dietary polyphenols, only few studies recognize chlorogenic acid (CGA) as a potential partner in combination therapy, while, conversely, its anticancer evidence is steadily growing, ultimately in OS. On this basis, herein we examine the cooperating effects between CGA and Doxo in U2OS and MG-63 human OS cells. With respect to Doxo alone, the concomitant administration of CGA further decreased cell viability and growth, promoting cell death potentially via apoptosis induction. Furthermore, a longer-lasting reduction in clonogenic potential deeply supported the CGA ability to improve Doxo efficacy in those cells. Remarkably, CGA treatment ameliorated Doxo-induced cytotoxicity in H9c2 rat cardiomyocyte cells instead. Although inactivation of p44/42 MAPK was detected in response to CGA plus Doxo, PD98059-mediated p44/42 MAPK impairment enhanced the combination outcome in OS cells. These findings firstly propose CGA as a promising chemosensitizer and cardioprotective agent in OS therapy, suggesting the p44/42 MAPK pathway as relevantly involved in CGA-mediated Doxo susceptibility. 相似文献
57.
Pawel Wolski Krzysztof Nieszporek Tomasz Panczyk 《International journal of molecular sciences》2021,22(16)
This works deals with analysis of properties of a carbon nanotube, the tips of which were functionalized by short cytosine-rich fragments of ssDNA. That object is aimed to work as a platform for storage and controlled release of doxorubicin in response to pH changes. We found that at neutral pH, doxorubicin molecules can be intercalated between the ssDNA fragments, and formation of such knots can effectively block other doxorubicin molecules, encapsulated in the nanotube interior, against release to the bulk. Because at the neutral pH, the ssDNA fragments are in form of random coils, the intercalation of doxorubicin is strong. At acidic pH, the ssDNA fragments undergo folding into i-motifs, and this leads to significant reduction of the interaction strength between doxorubicin and other components of the system. Thus, the drug molecules can be released to the bulk at acidic pH. The above conclusions concerning the storage/release mechanism of doxorubicin were drawn from the observation of molecular dynamics trajectories of the systems as well as from analysis of various components of pair interaction energies. 相似文献
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Novel carboxymethyl derivatives of chitin and chitosan materials and their biomedical applications 总被引:1,自引:0,他引:1
R. Jayakumar M. Prabaharan S. Tokura N. Selvamurugan 《Progress in Materials Science》2010,55(7):675-1993
Chitin and chitosan are natural biopolymers that are non-toxic, biodegradable and biocompatible. In the last decade, chitin and chitosan derivatives have garnered significant interest in the biomedical and biopharmaceutical research fields with applications as biomaterials for tissue engineering and wound healing and as excipients for drug delivery. Introducing small chemical groups to the chitin or chitosan structure, such as alkyl or carboxymethyl groups, can drastically increase the solubility of chitin and chitosan at neutral and alkaline pH values without affecting their characteristics; substitution with carboxyl groups can yield polymers with polyampholytic properties. Carboxymethyl derivatives of chitin and chitosan have shown promise for adsorbing metal ions, as drug delivery systems, in wound healing, as anti-microbial agents, in tissue engineering, as components in cosmetics and food and for anti-tumor activities. This review will focus on the preparative methods and applications of carboxymethyl and succinyl derivatives of chitin and chitosan with particular emphasis on their uses as materials for biomedical applications. 相似文献
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Nisaraporn Suthiwangcharoen Tao Li Kai Li Preston Thompson Shaojin You Qian Wang 《Nano Research》2011,4(5):483-493
Poly(caprolactone-b-2-vinylpyridine) (PCL-P2VP) coated with folate-conjugated M13 (FA-M13) provides a nanosized delivery system which is capable
of encapsulating hydrophobic antitumor drugs such as doxorubicin (DOX). The DOX-loaded FA-M13-PCL-P2VP assemblies had an average
diameter of approximately 200 nm and their structure was characterized using transmission electron microscopy, scanning electron
microscopy, and dynamic light scattering. The particles were stable at physiological pH but could be degraded at a lower pH.
The release of DOX from the nanoassemblies under acidic conditions was shown to be significantly faster than that observed
at physiological pH. In addition, the DOX-loaded FA-M13-PCL-P2VP particles showed a distinctly greater cellular uptake and
cytotoxicity against folate-receptor-positive cancer cells than folate-receptor-negative cells, indicating that the receptor
facilitates folate uptake via receptor-mediated endocytosis. Furthermore, the DOX-loaded particles also had a significantly
higher tumor uptake and selectivity compared to free DOX. This study therefore offers a new way to fabricate nanosized drug
delivery vehicles. 相似文献
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