共查询到20条相似文献,搜索用时 31 毫秒
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Cuie Chen Li Zhou Jie Geng Jinsong Ren Xiaogang Qu 《Small (Weinheim an der Bergstrasse, Germany)》2013,9(16):2793-2800
A novel light‐operated vehicle for targeted intracellular drug delivery is constructed using photosensitizer‐incorporated G‐quadruplex DNA‐capped mesoporous silica nanoparticles. Upon light irradiation, the photosensitizer generates ROS, causing the DNA capping to be cleaved and allowing cargo to be released. Importantly, this platform makes it possible to develop a drug‐carrier system for the synergistic combination of chemotherapy and PDT for cancer treatment with spatial/temporal control. Furthermore, the introducing of targeting ligands further improves tumor targeting efficiency. The excellent biocompatibility, cell‐specific intracellular drug delivery, and cellular uptake properties set up the basis for future biomedical application that require in vivo controlled, targeted drug delivery. 相似文献
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Epirubicin‐Loaded Superparamagnetic Iron‐Oxide Nanoparticles for Transdermal Delivery: Cancer Therapy by Circumventing the Skin Barrier
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Yue‐feng Rao Wei Chen Xing‐guang Liang Yong‐zhuo Huang Jing Miao Lin Liu Yan Lou Xing‐guo Zhang Ben Wang Rui‐kang Tang Zhong Chen Xiao‐yang Lu 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(2):239-247
The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron‐oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI–SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI–SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g?1. They feature specific pH‐sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose‐dependent. In vitro transdermal studies demonstrate that the EPI–SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic‐field‐assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION‐based vector for feasible transdermal therapy of skin cancer. 相似文献
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ROS‐Responsive Polyprodrug Nanoparticles for Triggered Drug Delivery and Effective Cancer Therapy
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Xiaoding Xu Phei Er Saw Wei Tao Yujing Li Xiaoyuan Ji Sushant Bhasin Yanlan Liu Dana Ayyash Jonathan Rasmussen Marc Huo Jinjun Shi Omid C. Farokhzad 《Advanced materials (Deerfield Beach, Fla.)》2017,29(33)
The application of nanoparticles (NPs) to drug delivery has led to the development of novel nanotherapeutics for the treatment of various diseases including cancer. However, clinical use of NP‐mediated drug delivery has not always translated into improved survival of cancer patients, in part due to the suboptimal properties of NP platforms, such as premature drug leakage during preparation, storage, or blood circulation, lack of active targeting to tumor tissue and cells, and poor tissue penetration. Herein, an innovative reactive oxygen species (ROS)‐responsive polyprodrug is reported that can self‐assemble into stable NPs with high drug loading. This new NP platform is composed of the following key components: (i) polyprodrug inner core that can respond to ROS for triggered release of intact therapeutic molecules, (ii) polyethylene glycol (PEG) outer shell to prolong blood circulation; and (iii) surface‐encoded internalizing RGD (iRGD) to enhance tumor targeting and tissue penetration. These targeted ROS‐responsive polyprodrug NPs show significant inhibition of tumor cell growth both in vitro and in vivo. 相似文献
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Dong Xiao Hui‐Zhen Jia Jing Zhang Chen‐Wei Liu Ren‐Xi Zhuo Xian‐Zheng Zhang 《Small (Weinheim an der Bergstrasse, Germany)》2014,10(3):591-598
A novel pH‐ and redox‐ dual‐responsive tumor‐triggered targeting mesoporous silica nanoparticle (TTTMSN) is designed as a drug carrier. The peptide RGDFFFFC is anchored on the surface of mesoporous silica nanoparticles via disulfide bonds, which are redox‐responsive, as a gatekeeper as well as a tumor‐targeting ligand. PEGylated technology is employed to protect the anchored peptide ligands. The peptide and monomethoxypolyethylene glycol (MPEG) with benzoic‐imine bond, which is pH‐sensitive, are then connected via “click” chemistry to obtain TTTMSN. In vitro cell research demonstrates that the targeting property of TTTMSN is switched off in normal tissues with neutral pH condition, and switched on in tumor tissues with acidic pH condition after removing the MPEG segment by hydrolysis of benzoic‐imine bond under acidic conditions. After deshielding of the MPEG segment, the drug‐loaded nanoparticles are easily taken up by tumor cells due to the exposed peptide targeting ligand, and subsequently the redox signal glutathione in tumor cells induces rapid drug release intracellularly after the cleavage of disulfide bond. This novel intelligent TTTMSN drug delivery system has great potential for cancer therapy. 相似文献
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Light‐Triggered Biomimetic Nanoerythrocyte for Tumor‐Targeted Lung Metastatic Combination Therapy of Malignant Melanoma
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Wen Liu Miaoliang Ruan Yanming Wang Rongguang Song Xin Ji Jiake Xu Jian Dai Wei Xue 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(38)
Red blood cell (RBC) membrane‐cloaked nanoparticles, reserving the intact cell membrane structure and membrane protein, can gain excellent cell‐specific functions such as long blood circulation and immune escape, providing a promising therapy nanoplatform for drug delivery. Herein, a novel RBC membrane biomimetic combination therapeutic system with tumor targeting ability is constructed by embedding bovine serum albumin (BSA) encapsulated with 1,2‐diaminocyclohexane‐platinum (II) (DACHPt) and indocyanine green (ICG) in the targeting peptide‐modified erythrocyte membrane (R‐RBC@BPtI) for enhancing tumor internalization and synergetic chemophototherapy. R‐RBC@BPtI displays excellent stability and high encapsulation efficiency with multiple cores enveloped in the membrane. Benefited from the stealth functionality and targeting modification of erythrocyte membranes, R‐RBC@BPtI can significantly promote tumor targeting and cellular uptake. Under the near‐infrared laser stimuli, R‐RBC@BPtI presents remarkable instability by singlet oxygen and heat‐mediated cleavage so as to trigger effective drug release, thereby achieving deep penetration and accumulation of DACHPt and ROS in the tumor site. Consequently, R‐RBC@BPtI with tumor‐specific targeting ability accomplishes remarkable ablation of tumors and suppressed lung metastasis in vivo by photothermal and chemotherapy combined ablation under phototriggering. This research provides a novel strategy of targeted biomimetic nanoplatforms for combined cancer chemotherapy–phototherapy. 相似文献
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Dual‐pH Sensitive Charge‐Reversal Polypeptide Micelles for Tumor‐Triggered Targeting Uptake and Nuclear Drug Delivery
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Shi‐Song Han Ze‐Yong Li Jing‐Yi Zhu Kai Han Zheng‐Yang Zeng Wei Hong Wen‐Xin Li Hui‐Zhen Jia Yun Liu Ren‐Xi Zhuo Xian‐Zheng Zhang 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(21):2543-2554
A novel dual‐pH sensitive charge‐reversal strategy is designed to deliver antitumor drugs targeting to tumor cells and to further promote the nuclei internalization by a stepwise response to the mildly acidic extracellular pH (≈6.5) of a tumor and endo/lysosome pH (≈5.0). Poly(l ‐lysine)‐block–poly(l ‐leucine) diblock copolymer is synthesized and the lysine amino residues are amidated by 2,3‐dimethylmaleic anhydride to form β‐carboxylic amide, making the polypeptides self‐assemble into negatively charged micelles. The amide can be hydrolyzed when exposed to the mildly acidic tumor extracellular environment, which makes the micelles switch to positively charged and they are then readily internalized by tumor cells. A nuclear targeting Tat peptide is further conjugated to the polypeptide via a click reaction. The Tat is amidated by succinyl chloride to mask its positive charge and cell‐penetrating function and thus to inhibit nonspecific cellular uptake. After the nanoparticles are internalized into the more acidic intracellular endo/lysosomes, the Tat succinyl amide is hydrolyzed to reactivate the Tat nuclear targeting function, promoting nanoparticle delivery into cell nuclei. This polypeptide nanocarrier facilitates tumor targeting and nuclear delivery simultaneously by simply modifying the lysine amino residues of polylysine and Tat into two different pH‐sensitive β‐carboxylic amides. 相似文献
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Immune Cell‐Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery
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Zhiwei Xie Yixue Su Gloria B. Kim Erhan Selvi Chuying Ma Virginia Aragon‐Sanabria Jer‐Tsong Hsieh Cheng Dong Jian Yang 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(10)
Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell‐mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer‐specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP‐PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti‐BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP‐PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP‐PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell–cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The “self‐powered” immune cell‐mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies. 相似文献
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Dose‐Dependent Therapeutic Distinction between Active and Passive Targeting Revealed Using Transferrin‐Coated PGMA Nanoparticles
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Ruhani Singh Marck Norret Michael J. House Yuriy Galabura Michael Bradshaw Diwei Ho Robert C. Woodward Timothy G. St. Pierre Igor Luzinov Nicole M. Smith Lee Yong Lim Killugudi Swaminathan Iyer 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(3):351-359
The paradigm of using nanoparticle‐based formulations for drug delivery relies on their enhanced passive accumulation in the tumor interstitium. Nanoparticles with active targeting capabilities attempt to further enhance specific delivery of drugs to the tumors via interaction with overexpressed cellular receptors. Consequently, it is widely accepted that drug delivery using actively targeted nanoparticles maximizes the therapeutic benefit and minimizes the off‐target effects. However, the process of nanoparticle mediated active targeting initially relies on their passive accumulation in tumors. In this article, it is demonstrated that these two tumor‐targeted drug delivery mechanisms are interrelated and dosage dependent. It is reported that at lower doses, actively targeted nanoparticles have distinctly higher efficacy in tumor inhibition than their passively targeted counterparts. However, the enhanced permeability and retention effect of the tumor tissue becomes the dominant factor influencing the efficacy of both passively and actively targeted nanoparticles when they are administered at higher doses. Importantly, it is demonstrated that dosage is a pivotal parameter that needs to be taken into account in the assessment of nanoparticle mediated targeted drug delivery. 相似文献
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Low‐Density Lipoprotein‐Mimicking Nanoparticles for Tumor‐Targeted Theranostic Applications
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Jeong Yu Lee Jin‐Ho Kim Ki Hyun Bae Mi Hwa Oh Youngwook Kim Jee Seon Kim Tae Gwan Park Keunchil Park Jung Hee Lee Yoon Sung Nam 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(2):222-231
This study introduces multifunctional lipid nanoparticles (LNPs), mimicking the structure and compositions of low‐density lipoproteins, for the tumor‐targeted co‐delivery of anti‐cancer drugs and superparamagnetic nanocrystals. Paclitaxel (4.7 wt%) and iron oxide nanocrystals (6.8 wt%, 11 nm in diameter) are co‐encapsulated within folate‐functionalized LNPs, which contain a cluster of nanocrystals with an overall diameter of about 170 nm and a zeta potential of about ‐40 mV. The folate‐functionalized LNPs enable the targeted detection of MCF‐7, human breast adenocarcinoma expressing folate receptors, in T2‐weighted magnetic resonance images as well as the efficient intracellular delivery of paclitaxel. Paclitaxel‐free LNPs show no significant cytotoxicity up to 0.2 mg mL?1, indicating the excellent biocompatibility of the LNPs for intracellular drug delivery applications. The targeted anti‐tumor activities of the LNPs in a mouse tumor model suggest that the low‐density lipoprotein‐mimetic LNPs can be an effective theranostic platform with excellent biocompatibility for the tumor‐targeted co‐delivery of various anti‐cancer agents. 相似文献
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Toxic Reactive Oxygen Species Enhanced Synergistic Combination Therapy by Self‐Assembled Metal‐Phenolic Network Nanoparticles
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Yunlu Dai Zhen Yang Siyuan Cheng Zhongliang Wang Ruili Zhang Guizhi Zhu Zhantong Wang Bryant C. Yung Rui Tian Orit Jacobson Can Xu Qianqian Ni Jibin Song Xiaolian Sun Gang Niu Xiaoyuan Chen 《Advanced materials (Deerfield Beach, Fla.)》2018,30(8)
Engineering functional nanomaterials with high therapeutic efficacy and minimum side effects has increasingly become a promising strategy for cancer treatment. Herein, a reactive oxygen species (ROS) enhanced combination chemotherapy platform is designed via a biocompatible metal‐polyphenol networks self‐assembly process by encapsulating doxorubicin (DOX) and platinum prodrugs in nanoparticles. Both DOX and platinum drugs can activate nicotinamide adenine dinucleotide phosphate oxidases, generating superoxide radicals (O2??). The superoxide dismutase‐like activity of polyphenols can catalyze H2O2 generation from O2??. Finally, the highly toxic HO? free radicals are generated by a Fenton reaction. The ROS HO? can synergize the chemotherapy by a cascade of bioreactions. Positron emission tomography imaging of 89Zr‐labeled as‐prepared DOX@Pt prodrug Fe3+ nanoparticles (DPPF NPs) shows prolonged blood circulation and high tumor accumulation. Furthermore, the DPPF NPs can effectively inhibit tumor growth and reduce the side effects of anticancer drugs. This study establishes a novel ROS promoted synergistic nanomedicine platform for cancer therapy. 相似文献
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ATP/pH Dual Responsive Nanoparticle with d‐[des‐Arg10]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery
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Yu Zhang Yifei Lu Feng Wang Sai An Yujie Zhang Tao Sun Jianhua Zhu Chen Jiang 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(3)
Inflammation has been reported as one significant hallmark of breast cancer in relation to tumor development, metastasis, and invasion. The bradykinin receptor 1 (B1R) is highly expressed on inflammatory breast tumor cells thus providing a promising targeting site for tumor recognition and sufficient receptor mediated endocytosis. In this study, the authors evaluate the targeting efficiency of l ‐form and d ‐form [des‐Arg10]kallidin both in vitro and in vivo. To further improve the drug delivery efficiency, the authors establish a dandelion like nanoparticle by combining the polymeric drug conjugates and aptamer complex together. The doxorubicin conjugated polymer is complexed with adenosine‐5′‐triphosphate (ATP) sensitive hybridized aptamer in self‐assembly process by intercalating into the double strand scaffolds. The acid labile conjugating bond and ATP sensitive aptamer endow the nanoparticle with dual responsiveness to intracellular milieu, thus triggering a quick drug release in tumor cells. Remarkable therapeutic effects and tuned in vivo pharmacokinetics profiles are shown by the aptamer complexed drug conjugates nanoparticle with B1R active targeting modification. Therefore the strategies of B1R targeting and ATP/pH dual‐responsiveness nanoparticle help achieve enhanced drug accumulation within tumor cells and efficient chemotherapy for breast cancer. 相似文献
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Programmed Nanococktail for Intracellular Cascade Reaction Regulating Self‐Synergistic Tumor Targeting Therapy
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Wei‐Hai Chen Guo‐Feng Luo Wen‐Xiu Qiu Qi Lei Sheng Hong Shi‐Bo Wang Di‐Wei Zheng Cheng‐Hui Zhu Xuan Zeng Jun Feng Si‐Xue Cheng Xian‐Zheng Zhang 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(6):733-744
In this work, a ZnO based nanococktail with programmed functions is designed and synthesized for self‐synergistic tumor targeting therapy. The nanococktail can actively target tumors via specific interaction of hyaluronic acid (HA) with CD44 receptors and respond to HAase‐rich tumor microenvironment to induce intracellular cascade reaction for controlled therapy. The exposed cell‐penetrating peptide (R8) potentiates the cellular uptake of therapeutic nanoparticles into targeted tumor cells. Then ZnO cocktail will readily degrade in acidic endo/lysosomes and induce the production of desired reactive oxygen species (ROS) in situ. The destructive ROS not only leads to serious cell damage but also triggers the on‐demand drug release for precise chemotherapy, thus achieving enhanced antitumor efficiency synergistically. After tail vein injection of ZnO cocktail, a favorable tumor apoptosis rate (71.2 ± 8.2%) is detected, which is significantly superior to that of free drug, doxorubicin (12.9 ± 5.2%). Both in vitro and in vivo studies demonstrate that the tailor‐made ZnO cocktail with favorable biocompatibility, promising tumor specificity, and self‐synergistically therapeutic capacity opens new avenues for cancer therapy. 相似文献
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Yongfei Li Mie Chen Bowen Yao Xun Lu Boyang Song Shauna N. Vasilatos Xiang Zhang Xiaomei Ren Chang Yao Weihe Bian Lizhu Sun 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(32)
Poor deep tumor penetration and incomplete intracellular drug release remain challenges for antitumor nanomedicine application in clinical settings. Herein, a nanomedicine (RLPA‐NPs) is developed that can achieve prolonged blood circulation, deep tumor penetration, active‐targeting of cancer cells, endosome/lysosome escape, and intracellular selectivity self‐amplified drug release for effective drug delivery. The RLPA‐NPs are constructed by encapsulation of a pH‐sensitive polymer octadecylamine‐poly(aspartate‐1‐(3‐aminopropyl) imidazole) (OA‐P(Asp‐API)) and a ROS‐generation agent, β‐Lapachone (Lap), in micelles assembled by the tumor‐penetration peptide internalizing RGD (iRGD)‐modified ROS‐responsive paclitaxel (PTX)‐prodrug. iRGD could promote RLPA‐NPs penetration into deep tumor tissue, and specific targeting to cancer cells. After internalization by cancer cells through receptor‐mediated endocytosis, OA‐P(Asp‐API) can rapidly protonate in the endosome's acidic environment, resulting in RLPA‐NPs escape from the endosome through the “proton sponge effect”. At the same time, the RLPA‐NPs micelle disassembles, releasing Lap and PTX‐prodrug. Subsequently, the released Lap could generate ROS, consequently amplifying and accelerating PTX release to kill tumor cells. The in vitro and in vivo studies demonstrated that RLPA‐NPs can significantly improve the therapeutic effect compared to control groups. Therefore, RLPA‐NPs are a promising nanoplatform for overcoming multiple physiological and pathological barriers to enhance drug delivery. 相似文献
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Tumor‐Targeting Multifunctional Rattle‐Type Theranostic Nanoparticles for MRI/NIRF Bimodal Imaging and Delivery of Hydrophobic Drugs
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Yunfeng Jiao Yangfei Sun Xiaoling Tang Qingguang Ren Wuli Yang 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(16):1962-1974
The development of theranostic systems capable of diagnosis, therapy, and target specificity is considerably significant for accomplishing personalized medicine. Here, a multifunctional rattle‐type nanoparticle (MRTN) as an effective biological bimodal imaging and tumor‐targeting delivery system is fabricated, and an enhanced loading ability of hydrophobic anticancer drug (paclitaxel) is also realized. The rattle structure with hydrophobic Fe3O4 as the inner core and mesoporous silica as the shell is obtained by one‐step templates removal process, and the size of interstitial hollow space can be easily adjusted. The Fe3O4 core with hydrophobic poly(tert‐butyl acrylate) (PTBA) chains on the surface is not only used as a magnetic resonance imaging (MRI) agent, but contributes to improving hydrophobic drug loading amount. Transferrin (Tf) and a near‐infrared fluorescent dye (Cy 7) are successfully modified on the surface of the nanorattle to increase the ability of near‐infrared fluorescence (NIRF) imaging and tumor‐targeting specificity. In vivo studies show the selective accumulation of MRTN in tumor tissues by Tf‐receptor‐mediated endocytosis. More importantly, paclitaxel‐loaded MRTN shows sustained release character and higher cytotoxicity than the free paclitaxel. This theranostic nanoparticle as an effective MRI/NIRF bimodal imaging probe and drug delivery system shows great potential in cancer diagnosis and therapy. 相似文献
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Yongyan Deng Fan Jia Xiaohui Chen Qiao Jin Jian Ji 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(23)
Mitochondria, which are important mediators for cancer initiation, growth, metastasis, and drug resistance, have been considered as a major target in cancer therapy. Herein, an acid‐activated mitochondria‐targeted drug nanocarrier is constructed for precise delivery of nitric oxide (NO) as an adenosine triphosphate (ATP) suppressor to amplify the therapeutic efficacy in cancer treatments. By combining α‐cyclodextrin (α‐CD) and acid‐cleavable dimethylmaleic anhydride modified PEG conjugated mitochondria‐targeting peptide, the nanocarrier shows prolonged blood circulation time and enhanced cellular uptake together with selectively restoring mitochondria‐targeting capability under tumor extracellular pH (6.5). Such specific mitochondria‐targeted delivery of NO proves crucial in inducing mitochondria dysfunction through facilitating mitochondrial membrane permeabilization and downregulating ATP level, which can inhibit P‐glycoprotein‐related bioactivities and formation of tumor‐derived microvesicles to combat drug resistance and cancer metastasis. Therefore, this pioneering acid‐activated mitochondria‐targeted NO nanocarrier is supposed to be a malignant tumor opponent and may provide insights for diverse NO‐relevant cancer treatments. 相似文献
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Selective CXCR4+ Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
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Raquel Díaz Victor Pallarès Olivia Cano‐Garrido Naroa Serna Laura Sánchez‐García Aïda Falgàs Mireia Pesarrodona Ugutz Unzueta Alejandro Sánchez‐Chardi Julieta M. Sánchez Isolda Casanova Esther Vázquez Ramón Mangues Antonio Villaverde 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(26)
Under the unmet need of efficient tumor‐targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22‐mRTA‐H6) is engineered to self‐assemble as protein‐only, CXCR4‐targeted nanoparticles. The soluble version of the construct self‐organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4+ cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor‐dependent mechanism of cytotoxicity. The insoluble version of T22‐mRTA‐H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22‐mRTA‐H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22‐mRTA‐H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self‐mediated intracellular drug delivery. 相似文献
19.
Vivian Juang Chih‐Hsien Chang Chen‐Shen Wang Hsin‐Ell Wang Yu‐Li Lo 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(49)
Irinotecan is one of the main chemotherapeutic agents for colorectal cancer (CRC). MicroRNA‐200 (miR‐200) has been reported to inhibit metastasis in cancer cells. Herein, pH‐sensitive and peptide‐modified liposomes and solid lipid nanoparticles (SLN) are designed for encapsulation of irinotecan and miR‐200, respectively. These peptides include one cell‐penetrating peptide, one ligand targeted to tumor neovasculature undergoing angiogenesis, and one mitochondria‐targeting peptide. The peptide‐modified nanoparticles are further coated with a pH‐sensitive PEG‐lipid derivative with an imine bond. These specially‐designed nanoparticles exhibit pH‐responsive release, internalization, and intracellular distribution in acidic pH of colon cancer HCT116 cells. These nanoparticles display low toxicity to blood and noncancerous intestinal cells. Delivery of miR‐200 by SLN further increases the cytotoxicity of irinotecan‐loaded liposomes against CRC cells by triggering apoptosis and suppressing RAS/β‐catenin/ZEB/multiple drug resistance (MDR) pathways. Using CRC‐bearing mice, the in vivo results further indicate that irinotecan and miR‐200 in pH‐responsive targeting nanoparticles exhibit positive therapeutic outcomes by inhibiting colorectal tumor growth and reducing systemic toxicity. Overall, successful delivery of miR and chemotherapy by multifunctional nanoparticles may modulate β‐catenin/MDR/apoptosis/metastasis signaling pathways and induce programmed cancer cell death. Thus, these pH‐responsive targeting nanoparticles may provide a potential regimen for effective treatment of colorectal cancer. 相似文献
20.
Bioinspired Nano‐Prodrug with Enhanced Tumor Targeting and Increased Therapeutic Efficiency
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Wei‐Hai Chen Qi Lei Cai‐Xia Yang Hui‐Zhen Jia Guo‐Feng Luo Xiao‐Yong Wang Gang Liu Si‐Xue Cheng Xian‐Zheng Zhang 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(39):5230-5242
Nanotechnology‐based drug delivery has a great potential to revolutionize cancer treatment by enhancing anticancer drug efficacy and reducing drug toxicity. Here, a bioinspired nano‐prodrug (BiNp) assembled by an antineoplastic peptidic derivative (FA‐KLA‐Hy‐DOX), a folate acid (FA)‐incorporated proapoptotic peptide (KLAKLAK)2 (KLA) to doxorubicin (DOX) via an acid‐labile hydrozone bond (Hy) is constructed. The hydrophobic antineoplastic agent DOX is efficiently shielded in the core of nano‐prodrug. With FA targeting moieties on the surface, the obtained BiNp shows significant tumor‐targeting ability and enhances the specific uptake of cancer cells. Upon the trigger by the intracellular acidic microenvironment of endosomes, the antineoplastic agent DOX is released on‐demand and promotes the apoptosis of cancer cells. Simultaneously, the liberated FA‐KLA can induce the dysfunction of mitochondria and evoke mitochondria‐dependent apoptosis. In vitro and in vivo results show that the nano‐prodrug BiNp with integrated programmed functions exhibits remarkable inhibition of tumor and achieves a maximized therapeutic efficiency with a minimized side effect. 相似文献