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1.
Preparation of a Camptothecin Prodrug with Glutathione‐Responsive Disulfide Linker for Anticancer Drug Delivery
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Dr. Zhigang Xu Dongdong Wang Shuang Xu Dr. Xiaoyan Liu Prof. Dr. Xiaoyu Zhang Prof. Dr. Haixia Zhang 《化学:亚洲杂志》2014,9(1):199-205
We present here a novel camptothecin (CPT) prodrug based on polyethylene glycol monomethyl ether‐block‐poly(2‐methacryl ester hydroxyethyl disulfide‐graft‐CPT) (MPEG‐SS‐PCPT). It formed biocompatible nanoparticles (NPs) with diameters of approximately 122 nm with a CPT loading content as high as approximately 25 wt % in aqueous solution. In in vitro release studies, these MPEG‐SS‐PCPT NPs could undergo triggered disassembly and much faster release of CPT under glutathione (GSH) stimulus than in the absence of GSH. The CPT prodrug had high antitumor activity, and another anticancer drug, doxorubicin hydrochloride (DOX ? HCl), could also be introduced into the prodrug with a high loading amount. The DOX ? HCl‐loaded CPT prodrug could deliver two anticancer drugs at the same time to produce a collaborative cytotoxicity toward cancer cells, which suggested that this GSH‐responsive NP system might become a promising carrier to improve drug‐delivery efficacy. 相似文献
2.
同载基因和药物的超微载体粒子的制备及体外评价 总被引:4,自引:0,他引:4
以聚乳酸_乙醇酸共聚物 (PLGA)和自行制备的O_羧甲基壳聚糖 (O_CMC)为原料 ,以 5_氟尿嘧啶 (5 Fu)为抗癌药物模型 ,以反义EGFR(表皮生长因子受体 )为基因药物模型 ,构建与评价了同载抗癌药物与基因的复合功能纳米药物载体系统。同载超微粒子的平均粒径为 2 5 8 7nm ,粒径分布指数为 0 14 2 ,粒子表面 ξ电位为 - 10 6 7eV。同载超微粒子在PBS中的释药行为研究表明 :超微粒子中 5_FU和基因均具有零级缓慢释放特性。体外肿瘤细胞存活率实验和免疫组化实验均证实同载超微粒子能高效抑制TJ90 5人脑胶质瘤细胞的增殖。最后用荧光共聚焦显微镜动态监测了超微粒子进入瘤细胞的转染过程 ,发现粒子可在不同时间内进入细胞浆和细胞核。 相似文献
3.
Jérémy Vuilleumier Geoffrey Gaulier Raphaël De Matos Yannick Mugnier Gabriel Campargue Jean-Pierre Wolf Luigi Bonacina Sandrine Gerber-Lemaire 《Helvetica chimica acta》2020,103(1):e1900251
While chemotherapy is one of the most used treatments in oncology, the systemic administration of chemotherapeutics generally results in undesired damages to healthy tissues and cells, side effects such as severe nausea and leukopenia, and reduced efficacy due to multidrug resistance and poor target accessibility. The limitations of conventional chemotherapy formulation have prompted the development of alternative nanomaterials-based strategies to achieve targeted and stimuli sensitive payload delivery to reach optimal local drug concentration at tumor sites. In this study, the anticancer drug chlorambucil (Clb) was conjugated to the surface of silica coated lithium niobate (LNO) harmonic nanoparticles (HNPs) using a photocaging tether based on coumarin-4-yl methyl derivative. Upon laser pulsed femtosecond irradiation at 790 nm, the second harmonic emission from the metal oxide core induced the efficient release of Clb, with concomitant contribution from the nonlinear absorption of the coumarin (CM)-based moiety. 相似文献
4.
We report the development of bioconjugated plasmonic vesicles assembled from SERS-encoded amphiphilic gold nanoparticles for cancer-targeted drug delivery. This new type of plasmonic assemblies with a hollow cavity can play multifunctional roles as delivery carriers for anticancer drugs and SERS-active plasmonic imaging probes to specifically label targeted cancer cells and monitor intracellular drug delivery. We have shown that the pH-responsive disassembly of the plasmonic vesicle, stimulated by the hydrophobic-to-hydrophilic transition of the hydrophobic brushes in acidic intracellular compartments, allows for triggered intracellular drug release. Because self-assembled plasmonic vesicles exhibit significantly different plasmonic properties and greatly enhanced SERS intensity in comparison with single gold nanoparticles due to strong interparticle plasmonic coupling, disassembly of the vesicles in endocytic compartments leads to dramatic changes in scattering properties and SERS signals, which can serve as independent feedback mechanisms to signal cargo release from the vesicles. The unique structural and optical properties of the plasmonic vesicle have made it a promising platform for targeted combination therapy and theranostic applications by taking advantage of recent advances in gold nanostructure based in vivo bioimaging and photothermal therapy and their loading capacity for both hydrophilic (nucleic acids and proteins) and hydrophobic (small molecules) therapeutic agents. 相似文献
5.
Miao Chen Wei-Guo Zhang Jia-Wei Li Chun-Yan Hong Wen-Jian Zhang Ye-Zi You 《中国科学:化学(英文版)》2018,61(9):1159-1166
pH- and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly (PISA). First, reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate (DIPEMA) and camptothecin prodrug monomer (CPTM) using biocompatible poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P (DIPEMA-co-CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate (BzMA) using the PHPMA-P(DIPEMA-co-CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell (PHPMA), the drug-conjugated middle layer (P(DIPEMA-co-CPTM)) and the PBzMA core, and relatively high concentration (250 mg/g). The prodrug nanoparticles can respond to two stimuli (reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin (CPT) within the prodrug nanoparticles could be effectively triggered. pH-Induced hydrophobic/ hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity. 相似文献
6.
Amaneh Javid Shahin Ahmadian Ali Akbar Saboury Seyed Mehdi Kalantar Saeed Rezaei-Zarchi Sughra Shahzad 《Applied biochemistry and biotechnology》2014,173(1):36-54
Magnetite nanoparticles are particularly attractive for drug delivery applications because of their size-dependent superparamagnetism, low toxicity, and biocompatibility with cells and tissues. Surface modification of iron oxide nanoparticles with biocompatible polymers is potentially beneficial to prepare biodegradable nanocomposite-based drug delivery agents for in vivo and in vitro applications. In the present study, the bare (10 nm) and polyethylene glycol (PEG)–(3-aminopropyl)triethoxysilane (APTES) (PA) modified (17 nm) superparamagnetic iron oxide nanoparticles (SPIO NPs) were synthesized by coprecipitation method. The anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately encapsulated into the synthesized polymeric nanocomposites for localized targeting of human ovarian cancer in vitro. Surface morphology analysis by scanning electron microscopy showed a slight increase in particle size (27?±?0.7 and 30?±?0.45 nm) with drug loading capacities of 70 and 61.5 % and release capabilities of 90 and 93 % for the DOX- and PTX-AP-SPIO NPs, respectively (p?<?0.001). Ten milligrams/milliliter DOX- and PTX-loaded AP-SPIO NPs caused a significant amount of cytotoxicity and downregulation of antiapoptotic proteins, as compared with same amounts of free drugs (p?<?0.001). In vivo antiproliferative effect of present formulation on immunodeficient female Balb/c mice showed ovarian tumor shrinkage from 2,920 to 143 mm3 after 40 days. The present formulation of APTES–PEG-SPIO-based nanocomposite system of targeted drug delivery proved to be effective enough in order to treat deadly solid tumor of ovarian cancer in vitro and in vivo. 相似文献
7.
Zn-loaded bovine serum albumin nanoparticles (Zn-BSA nanoparticles) were prepared and used as carriers for pH-responsive anticancer drug delivery. Zinc was introduced into this system to increase the stability of the BSA nanoparticles and to load the anticancer drug based on the coordination bonding formation of Zn-BSA and Zn-drug molecules, respectively. The cleavage of either the "Zn-BSA" or the "Zn-drug" coordination bonding, in response to pH, would result in the release of the drug under designated pH conditions. The nanoparticles were spherical with diameters of 50-60 nm and narrow size distribution. Mitoxantrone (MX) was chosen as the model drug to study the release behavior and the inhibitory efficacy against tumor cells. In vitro release behavior of MX loaded Zn-BSA nanoparticles (MX-Zn-BSA nanoparticles) showed a fine pH-responsiveness. The release amount at pH 5.0 was close to 80%, while the cumulative release amount at pH 7.4 was less than 6% within 24 h. The blank Zn-BSA nanoparticles were of low cytotoxicity, while a high cytotoxic activity of MX-Zn-BSA nanoparticles against MCF-7 cells was demonstrated by in vitro cell assays. 相似文献
8.
利用静电纺丝技术制备了负载亲水性药物阿霉素(DOX)以及疏水性药物喜树碱(CPT)的复合纳米纤维. 先用巯基封端的普朗尼克(F127)修饰纳米氧化锌(FZnO), 再将FZnO负载盐酸阿霉素(DOX@FZnO), 最后将DOX@FZnO与CPT一起纺入聚乳酸-乙醇酸(PLGA)纤维中. 体外药物释放结果表明, 复合纳米纤维能够减小亲水性药物的突释, 减缓药物释放速率, 延长药物释放时间. 体外细胞活性结果表明, 双载药复合纤维比单载药复合纤维具有更强的细胞毒性, 能够有效抑制癌细胞生长. 相似文献
9.
Hoyeon Lee Soojin Uhm Jung‐Won Shin Hyun Mi Jeon Sun Dongbang Hyo Sung Jung Yun‐Cheol Na Prof. Chulhun Kang Prof. Jong Seung Kim 《化学:亚洲杂志》2015,10(12):2695-2700
A galactose‐appended drug delivery system released camptothecin (CPT) to lysosomes of HepG2 hepatoma cells, resulting in the cell resistance to the anticancer drug. We found that the resistance to CPT is caused by alteration of the drug release from the prodrug in lysosomes, emphasizing that the final delivery locations may critically influence drug efficacy. 相似文献
10.
Xin‐Yu Zhao Prof. Dr. Ying‐Jie Zhu Feng Chen Bing‐Qiang Lu Chao Qi Jing Zhao Dr. Jin Wu 《化学:亚洲杂志》2013,8(6):1306-1312
Calcium phosphate hybrid nanoparticles (CaP‐HNPs) have been synthesized in aqueous solution through self‐assembly by using two oppositely charged polyelectrolytes (poly(diallyldimethylammonium chloride) (PDADMAC) and poly(acrylate sodium) (PAS)) as dual templates. First, the PAS/Ca2+ and PDADMAC/PO43? complexes form through electrostatic interactions and then two complexes self‐assemble into CaP‐HNPs after mixing them together. The as‐prepared CaP‐HNPs exhibit a spherical morphology with a narrow size distribution, good dispersibility, and high colloidal stability in water. The CaP‐HNPs are explored as a nanocarrier for the anticancer drug docetaxel (Dtxl). The CaP‐HNPs show excellent biocompatibility, high drug‐loading capacity, pH‐sensitive drug‐release behavior, and high anticancer effect after being loaded with Dtxl. Therefore, the as‐prepared CaP‐HNPs are promising drug nanocarriers for cancer therapy. 相似文献
11.
Lian HY Hu M Liu CH Yamauchi Y Wu KC 《Chemical communications (Cambridge, England)》2012,48(42):5151-5153
Highly biocompatible coordination polymer (Prussian Blue) nanoparticles (LC(50) > 1000 μg mL(-1)) with a hollow interior and a microporous framework (denoted as HPB) are utilized as an anticancer drug (i.e. cisplatin) capsule for chemotherapy of bladder cancer T24 cells. 相似文献
12.
《Angewandte Chemie (International ed. in English)》2017,56(42):12946-12951
Despite impressive recent advances in the synthesis of lead chalcogenide solid nanoparticles, there are no examples of lead chalcogenide hollow nanoparticles (HNPs) with controlled diameter and shell thickness as current synthetic approaches for HNPs have inherent limitations associated with their complexity, inability to precisely control the dimensions, and limited possibilities with regard to applicable materials. Herein, we report on an unconventional strategy for crafting uniform lead chalcogenide (PbS and PbTe) HNPs with tailorable size, surface chemistry, and near‐IR absorption. Amphiphilic star‐like triblock copolymers [polystyrene‐block‐poly(acrylic acid)‐block‐polystyrene and polystyrene‐block‐poly(acrylic acid)‐block‐poly(3,4‐ethylenedioxythiophene)] were rationally synthesized and exploited as nanoreactors for the formation of uniform PbS and PbTe HNPs. Compared to their solid counterparts, the near‐IR absorption of the HNPs is blue‐shifted owing to the hollow interior. This strategy can be readily extended to other types of intriguing low‐band‐gap HNPs for diverse applications. 相似文献
13.
《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(42):13126-13131
Despite impressive recent advances in the synthesis of lead chalcogenide solid nanoparticles, there are no examples of lead chalcogenide hollow nanoparticles (HNPs) with controlled diameter and shell thickness as current synthetic approaches for HNPs have inherent limitations associated with their complexity, inability to precisely control the dimensions, and limited possibilities with regard to applicable materials. Herein, we report on an unconventional strategy for crafting uniform lead chalcogenide (PbS and PbTe) HNPs with tailorable size, surface chemistry, and near‐IR absorption. Amphiphilic star‐like triblock copolymers [polystyrene‐block‐poly(acrylic acid)‐block‐polystyrene and polystyrene‐block‐poly(acrylic acid)‐block‐poly(3,4‐ethylenedioxythiophene)] were rationally synthesized and exploited as nanoreactors for the formation of uniform PbS and PbTe HNPs. Compared to their solid counterparts, the near‐IR absorption of the HNPs is blue‐shifted owing to the hollow interior. This strategy can be readily extended to other types of intriguing low‐band‐gap HNPs for diverse applications. 相似文献
14.
Prussian Blue Derived Nanoporous Iron Oxides as Anticancer Drug Carriers for Magnetic‐Guided Chemotherapy
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Mohamed B. Zakaria Dr. Alexei A. Belik Chia‐Hung Liu Han‐Yun Hsieh Yu‐Te Liao Dr. Victor Malgras Prof. Yusuke Yamauchi Prof. Kevin. C.‐W. Wu 《化学:亚洲杂志》2015,10(7):1457-1462
New nanoporous iron oxide nanoparticles with superparamagnetic behavior were successfully synthesized from Prussian blue (PB) nanocubes through a thermal conversion method and applied to the intracellular drug‐delivery systems (DDS) of bladder cancer cells (i.e., T24) with controlled release and magnetic guiding properties. The results of the MTT assay and confocal laser scanning microscopy indicate that the synthesized iron oxide nanoparticles were successfully uptaken by T24 cells with excellent biocompatibility. An anticancer drug, that is, cisplatin, was used as a model drug, and its loading/release behavior was investigated. The intracellular drug delivery efficiency was greatly enhanced for the cisplatin‐loaded, PB‐derived, magnetic‐guided drug‐delivery system compared with the non‐drug case. The synthesized nanomaterials show great potential as drug vehicles with high biocompatibility, controlled release, and magnetic targeting features for future intracellular DDS. 相似文献
15.
Ceramic-based nanoparticles entrapping water-insoluble photosensitizing anticancer drugs: a novel drug-carrier system for photodynamic therapy 总被引:10,自引:0,他引:10
Roy I Ohulchanskyy TY Pudavar HE Bergey EJ Oseroff AR Morgan J Dougherty TJ Prasad PN 《Journal of the American Chemical Society》2003,125(26):7860-7865
A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drug-carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter approximately 30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated. 相似文献
16.
Dr. Gabriel Martínez-Edo Dr. Evelyn Y. Xue Dr. Summer Y. Y. Ha Iris Pontón Dr. José Antonio González-Delgado Prof. Dr. Salvador Borrós Prof. Dr. Tomás Torres Prof. Dr. Dennis K. P. Ng Prof. Dr. David Sánchez-García 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(59):14610-14618
A pH-responsive drug delivery system (DDS) based on mesoporous silica nanoparticles (MSNs) has been prepared for the delivery of three anticancer drugs with different modes of action. The novelty of this system is its ability to combine synergistic chemotherapy and photodynamic therapy. A photoactive conjugate of a phthalocyanine (Pc) and a topoisomerase I inhibitor (topo-I), namely camptothecin (CPT), linked by a poly(ethylene glycol) (PEG) chain has been synthesized and then loaded into the mesopores of MSNs. Doxorubicin (DOX), which is a topoisomerase II inhibitor (topo-II), has also been covalently anchored to the outer surface of the MSNs through a dihydrazide PEG linker. In the acidic environment of tumor cells, selective release of the three drugs takes place. In vitro studies have demonstrated the endocytosis of the system into HeLa and HepG2 cells, and the subsequent release of the three drugs into the cytoplasm and nucleus. Furthermore, the cytotoxic effect of DOX, CPT and Pc has been assessed in vitro before and upon light irradiation. 相似文献
17.
Amphiphilic block copolymers, methoxy poly(ethylene glycol)-b-poly(valerolactone) (mPEG-b-PVL), were synthesized via ring opening polymerization of δ-valerolactone in the presence of methoxy poly(ethylene glycol) (mPEG). The copolymers form micelle-like nanoparticles by their amphiphilic characteristics and their structures were examined by Nuclear Magnetic Resonance (NMR). The sizes of nanoparticles ranged from 60 to 120 nm as measured by dynamic light scattering detection, and were larger with higher molecular weight of the copolymers. The Critical Micelle Concentration (CMC) of these nanoparticles in water decreased with increasing molecular weight of hydrophobic segment. Stability analysis showed that the micellar solutions maintain their sizes at 37 °C for six weeks without aggregation or dissociation. The lyophilization method was better than the evaporation method when camptothecin (CPT) was incorporated to the micelles. The former method yielded higher CPT loading efficiency and lower aggregation. The loading efficiency of CPT could be more than 96% and a steady release rate of CPT was kept for twenty six days. Moreover, the mPEG-b-PVL polymeric micelles offered good protection of CPT lactone form at 37 °C for sixteen days. The copolymers showed no cytotoxicity towards L929 mouse muscular cells when incubated for one day. Taken together, the mPEG-b-PVL copolymer has potential to be used for the delivery of CPT or other similar drugs. 相似文献
18.
Biomineralization of Versatile CuS/Gd2O3 Hybrid Nanoparticles for MR Imaging and Antitumor Photothermal Chemotherapy
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Huai‐Xin Zhao Hong Wang Quan Zou Dr. Shao‐Kai Sun Prof. Chunshui Yu Prof. Xuejun Zhang Dr. Yan‐Yan Fu 《化学:亚洲杂志》2016,11(17):2458-2469
The versatile application of nanoparticles in integrating imaging and therapy has aroused extensive research interest in precision medicine. Of the various nanoparticles that have been studied, CuS has shown great potential in the construction of multifunctional agents, owing to its excellent photothermal heating properties. Herein, we report a facile one‐pot biomineralization approach for the preparation of versatile bovine‐serum‐albumin‐conjugated CuS/Gd2O3 hybrid nanoparticles (BSA?CuS/Gd2O3 HNPs), which simultaneously possessed strong longitudinal relaxivity, an outstanding photothermal effect, high drug‐loading capacity, and pH/temperature‐responsive drug release. The versatile nanoparticles were used for magnetic resonance imaging (MRI) and antitumor photothermal chemotherapy, both in vitro and in vivo. In vivo MRI showed that the BSA?CuS/Gd2O3 HNPs had a long circulation time and effective passive tumor‐uptake ability. More importantly, combined in vitro and in vivo therapy demonstrated that drug‐loaded BSA?CuS/Gd2O3 HNPs offered outstanding synergistic therapeutic efficacy for tumor inhibition. 相似文献
19.
20.
Madeeha Shahzad Lodhi Fatima Khalid Muhammad Tahir Khan Zahoor Qadir Samra Shabbir Muhammad Yu-Juan Zhang Kejie Mou 《Molecules (Basel, Switzerland)》2022,27(1)
Therapeutic effects of anticancer medicines can be improved by targeting the specific receptors on cancer cells. Folate receptor (FR) targeting with antibody (Ab) is an effective tool to deliver anticancer drugs to the cancer cell. In this research project, a novel formulation of targeting drug delivery was designed, and its anticancer effects were analyzed. Folic acid-conjugated magnetic nanoparticles (MNPs) were used for the purification of folate receptors through a novel magnetic affinity purification method. Antibodies against the folate receptors and methotrexate (MTX) were developed and characterized with enzyme-linked immunosorbent assay and Western blot. Targeting nanomedicines (MNP-MTX-FR Ab) were synthesized by engineering the MNP with methotrexate and anti-folate receptor antibody (anti-FR Ab). The cytotoxicity of nanomedicines on HeLa cells was analyzed by calculating the % age cell viability. A fluorescent study was performed with HeLa cells and tumor tissue sections to analyze the binding efficacy and intracellular tracking of synthesized nanomedicines. MNP-MTX-FR Ab demonstrated good cytotoxicity along all the nanocomposites, which confirms that the antibody-coated medicine possesses the potential affinity to destroy cancer cells in the targeted drug delivery process. Immunohistochemical approaches and fluorescent study further confirmed their uptake by FRs on the tumor cells’ surface in antibody-mediated endocytosis. The current approach is a useful addition to targeted drug delivery for better management of cancer therapy along with immunotherapy in the future. 相似文献