共查询到20条相似文献,搜索用时 62 毫秒
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Ronnie H. Fang Ashley V. Kroll Liangfang Zhang 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(41):5483-5496
Immunotherapeutic approaches for treating cancer overall have been receiving a considerable amount of interest due to the recent approval of several clinical formulations. Among the different modalities, anticancer vaccination acts by training the body to endogenously generate a response against tumor cells. However, despite the large amount of work that has gone into the development of such vaccines, the near absence of clinically approved formulations highlights the many challenges facing those working in the field. The generation of potent endogenous anticancer responses poses unique challenges due to the similarity between cancer cells and normal, healthy cells. As researchers continue to tackle the limited efficacy of vaccine formulations, fresh and novel approaches are being sought after to address many of the underlying problems. Here the application of nanoparticle technology towards the development of anticancer vaccines is discussed. Specifically, there is a focus on the benefits of using such strategies to manipulate antigen presenting cells (APCs), which are essential to the vaccination process, and how nanoparticle‐based platforms can be rationally engineered to elicit appropriate downstream immune responses. 相似文献
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Vasudha Murlidhar Mina Zeinali Svetlana Grabauskiene Mostafa Ghannad‐Rezaie Max S. Wicha Diane M. Simeone Nithya Ramnath Rishindra M. Reddy Sunitha Nagrath 《Small (Weinheim an der Bergstrasse, Germany)》2014,10(23):4895-4904
Circulating tumor cells (CTCs) are believed to play an important role in metastasis, a process responsible for the majority of cancer‐related deaths. But their rarity in the bloodstream makes microfluidic isolation complex and time‐consuming. Additionally the low processing speeds can be a hindrance to obtaining higher yields of CTCs, limiting their potential use as biomarkers for early diagnosis. Here, a high throughput microfluidic technology, the OncoBean Chip, is reported. It employs radial flow that introduces a varying shear profile across the device, enabling efficient cell capture by affinity at high flow rates. The recovery from whole blood is validated with cancer cell lines H1650 and MCF7, achieving a mean efficiency >80% at a throughput of 10 mL h?1 in contrast to a flow rate of 1 mL h?1 standardly reported with other microfluidic devices. Cells are recovered with a viability rate of 93% at these high speeds, increasing the ability to use captured CTCs for downstream analysis. Broad clinical application is demonstrated using comparable flow rates from blood specimens obtained from breast, pancreatic, and lung cancer patients. Comparable CTC numbers are recovered in all the samples at the two flow rates, demonstrating the ability of the technology to perform at high throughputs. 相似文献
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Reassembly of 89Zr‐Labeled Cancer Cell Membranes into Multicompartment Membrane‐Derived Liposomes for PET‐Trackable Tumor‐Targeted Theranostics
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Bo Yu Shreya Goel Dalong Ni Paul A. Ellison Cerise M. Siamof Dawei Jiang Liang Cheng Lei Kang Faquan Yu Zhuang Liu Todd E. Barnhart Qianjun He Han Zhang Weibo Cai 《Advanced materials (Deerfield Beach, Fla.)》2018,30(13)
Nanoengineering of cell membranes holds great potential to revolutionize tumor‐targeted theranostics, owing to their innate biocompatibility and ability to escape from the immune and reticuloendothelial systems. However, tailoring and integrating cell membranes with drug and imaging agents into one versatile nanoparticle are still challenging. Here, multicompartment membrane‐derived liposomes (MCLs) are developed by reassembling cancer cell membranes with Tween‐80, and are used to conjugate 89Zr via deferoxamine chelator and load tetrakis(4‐carboxyphenyl) porphyrin for in vivo noninvasive quantitative tracing by positron emission tomography imaging and photodynamic therapy (PDT), respectively. Radiolabeled constructs, 89Zr‐Df‐MCLs, demonstrate excellent radiochemical stability in vivo, target 4T1 tumors by the enhanced permeability and retention effect, and are retained long‐term for efficient and effective PDT while clearing gradually from the reticuloendothelial system via hepatobiliary excretion. Toxicity evaluation confirms that the MCLs do not impose acute or chronic toxicity in intravenously injected mice. Additionally, 89Zr‐labeled MCLs can execute rapid and highly sensitive lymph node mapping, even for deep‐seated sentinel lymph nodes. The as‐developed cell membrane reassembling route to MCLs could be extended to other cell types, providing a versatile platform for disease theranostics by facilely and efficiently integrating various multifunctional agents. 相似文献
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Wei‐Hai Chen Guo‐Feng Luo Yang Sung Sohn Rachel Nechushtai Itamar Willner 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(17)
UiO‐68 metal–organic framework nanoparticles (NMOFs) are loaded with a doxorubicin drug (fluorescent dye analogs) and locked by means of structurally engineered duplex nucleic acid structures, where one strand is covalently linked to the NMOFs and the second strand is hybridized with the anchor strand. Besides the complementarity of the second strand to the anchor sequence, it includes the complementary sequence to the microRNAs (miRNA)‐21 or miRNA‐221 that is specific miRNA biomarker for MCF‐7 breast cancer cells or OVCAR‐3 ovarian cancer cells. In the presence of the respective miRNA biomarkers, the miRNA‐induced displacement of the strand associated with the anchor strand proceeds, resulting in the release of DNA/miRNA duplexes. The released duplexes are, however, engineered to be digested in the presence of exonuclease III, Exo III, a process that recycles the miRNAs and provides the autonomous amplified unlocking of the NMOFs and the release of the doxorubicin load (or the fluorescent dye analogs) even at low concentrations of miRNA. Preliminary cell experiments reveal that the respective NMOFs are unlocked by the miRNA‐21 or miRNA‐221, resulting in selective cytotoxicity toward MCF‐7 breast cancer cells or OVCAR‐3 ovarian cancer cells. 相似文献
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Zi Ying Lingyan Feng Dongqing Ji Yuan Zhang Wei Chen Yifan Dai Metini Janyasupab Xinxin Li Weijia Wen Chung‐Chiun Liu 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(18)
Alpha‐methylacyl‐CoA racemase (AMACR) has been proven to be consistently overexpressed in prostate cancer epitheliums, and is expected to act as a positive biomarker for the diagnosis of prostate carcinoma in clinical practice. Here, a strategy for specific determination of AMACR in real human serum by using an electrochemical microsensor system is presented. In order to implement the protocol, a self‐organized nanohybrid consisting of metal nanopillars in a 2D MoS2 matrix is developed as material for the sensing interface. The testing signal outputs are strongly enhanced with the presence of the nanohybrids owing to that the metal pillars provide an efficient mass difussion and electron transfer path to the MoS2 film surface. Furthermore, the phase‐regulated sensing mechanism over MoS2 is noticed and demonstrated by density functional theory calculation and experiments. The explored MoS2 based nanohybrids are employed for the fabrication of an electrochemical microsensor, presenting good linear relationship in both ng µL?1 and pg µL?1 ranges for AMACR quantification. The sampling analysis of human serum indicates that this microsensor has good diagnostic specificity and sensitivity toward AMACR. The proposed electrochemical microsensor system also demonstrates the advantages of convenience, cost‐effectiveness, and disposability, resulting in a potential integrated microsystem for point‐of‐care prostate cancer diagnosis. 相似文献
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Anujan Ramesh Sahana Kumar Dipika Nandi Ashish Kulkarni 《Advanced materials (Deerfield Beach, Fla.)》2019,31(51)
Immune modulation of macrophages has emerged as an attractive approach for anti‐cancer therapy. However, there are two main challenges in successfully utilizing macrophages for immunotherapy. First, macrophage colony stimulating factor (MCSF) secreted by cancer cells binds to colony stimulating factor 1 receptor (CSF1‐R) on macrophages and in turn activates the downstream signaling pathway responsible for polarization of tumor‐associated macrophages (TAMs) to immunosuppressive M2 phenotype. Second, ligation of signal regulatory protein α (SIRPα) expressed on myeloid cells to CD47, a transmembrane protein overexpressed on cancer cells, activates the Src homology region 2 (SH2) domain ‐phosphatases SHP‐1 and SHP‐2 in macrophages. This results in activation of “eat‐me‐not” signaling pathway and inhibition of phagocytosis. Here, it is reported that self‐assembled dual‐inhibitor‐loaded nanoparticles (DNTs) target M2 macrophages and simultaneously inhibit CSF1R and SHP2 pathways. This results in efficient repolarization of M2 macrophages to an active M1 phenotype, and superior phagocytic capabilities as compared to individual drug treatments. Furthermore, suboptimal dose administration of DNTs in highly aggressive breast cancer and melanoma mouse models show enhanced anti‐tumor efficacy without any toxicity. These studies demonstrate that the concurrent inhibition of CSF1‐R and SHP2 signaling pathways for macrophage activation and phagocytosis enhancement could be an effective strategy for macrophage‐based immunotherapy. 相似文献
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Tianyu Du Chunqiu Zhao Fawad ur Rehman Lanmei Lai Xiaoqi Li Yi Sun Shouhua Luo Hui Jiang Matthias Selke Xuemei Wang 《Nano Research》2017,10(8):2626-2632
Early diagnosis remains highly important for efficient cancer treatment,and hence,there is significant interest in the development of effective imaging strategies.This work reports a new multimodal bioimaging method for accurate and rapid diagnosis of cancer cells by introducing aqueous Fe2+ and Zn2+ ions into cancer cells (i.e.,HeLa,U87,and HepG2 cancer cells).We found that the biocompatible metal ions Fe2+ and Zn2+ forced the cancer cells to spontaneously synthesize fluorescent ZnO nanoclusters and magnetic Fe3O4 nanoclusters.These clusters could then be used for multimodal cancer imaging by combining fluorescence imaging with magnetic resonance imaging and computed tomography imaging.Meanwhile,for normal cells (i.e.,L02) and tissues,neither fluorescence nor any other obvious difference could be detected between preand post-injection.This multimodal bioimaging strategy based on the in situ biosynthesized Zn&Fe oxide nanoclusters might therefore be useful for early cancer diagnosis and therapy. 相似文献
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pH‐ and NIR Light‐Responsive Polymeric Prodrug Micelles for Hyperthermia‐Assisted Site‐Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment
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Zuhong Li Haibo Wang Yangjun Chen Yin Wang Huan Li Haijie Han Tingting Chen Qiao Jin Jian Ji 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(20):2731-2740
Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR‐780 loaded pH‐responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine‐based biomimetic micellar shell and acid‐sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site‐specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX‐resistant MCF‐7/ADR cells. Meanwhile, the tumor site‐specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF‐7/ADR tumor growth in tumor‐bearing mice. These results demonstrate that the well‐designed IR‐780 loaded polymeric prodrug micelles for hyperthermia‐assisted site‐specific chemotherapy present an effective approach to reverse drug resistance. 相似文献
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Zhen Zhang Jing Wang Karthik Balaji Shanmugasundaram Belinda Yeo Andreas Mller Alain Wuethrich Lynlee L. Lin Matt Trau 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(13)
Epithelial–mesenchymal transition (EMT) is a primary mechanism for cancer metastasis. Detecting the activation of EMT can potentially convey signs of metastasis to guide treatment management and improve patient survival. One of the classic signatures of EMT is characterized by dynamic changes in cellular expression levels of E‐cadherin and N‐cadherin, whose soluble active fragments have recently been reported to be biomarkers for cancer diagnosis and prognosis. Herein, a microfluidic immunoassay (termed “SERS immunoassay”) based on sensitive and simultaneous detection of soluble E‐cadherin (sE‐cadherin) and soluble N‐cadherin (sN‐cadherin) for EMT monitoring in patients' plasma is presented. The SERS immunoassay integrates in situ nanomixing and surface‐enhanced Raman scattering readout to enable accurate detection of sE‐cadherin and sN‐cadherin from as low as 10 cells mL?1. This assay enables tracking of a concurrent decrease in sE‐cadherin and increase in sN‐cadherin in breast cancer cells undergoing drug‐induced mesenchymal transformation. The clinical potential of the SERS immunoassay is further demonstrated by successful detection of sE‐cadherin and sN‐cadherin in metastatic stage IV breast cancer patient plasma samples. The SERS immunoassay can potentially sense the activation of EMT to provide early indications of cancer invasions or metastasis. 相似文献
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Wei Feng Xiuguo Han Rongyan Wang Xiang Gao Ping Hu Wenwen Yue Yu Chen Jianlin Shi 《Advanced materials (Deerfield Beach, Fla.)》2019,31(5)
The tumor microenvironment (TME) has been increasingly recognized as a crucial contributor to tumorigenesis. Based on the unique TME for achieving tumor‐specific therapy, here a novel concept of photothermal‐enhanced sequential nanocatalytic therapy in both NIR‐I and NIR‐II biowindows is proposed, which innovatively changes the condition of nanocatalytic Fenton reaction for production of highly efficient hydroxyl radicals (?OH) and consequently suppressing the tumor growth. Evidence suggests that glucose plays a vital role in powering cancer progression. Encouraged by the oxidation of glucose to gluconic acid and H2O2 by glucose oxidase (GOD), an Fe3O4/GOD‐functionalized polypyrrole (PPy)‐based composite nanocatalyst is constructed to achieve diagnostic imaging‐guided, photothermal‐enhanced, and TME‐specific sequential nanocatalytic tumor therapy. The consumption of intratumoral glucose by GOD leads to the in situ elevation of the H2O2 level, and the integrated Fe3O4 component then catalyzes H2O2 into highly toxic ?OH to efficiently induce cancer‐cell death. Importantly, the high photothermal‐conversion efficiency (66.4% in NIR‐II biowindow) of the PPy component elevates the local tumor temperature in both NIR‐I and NIR‐II biowindows to substaintially accelerate and improve the nanocatalytic disproportionation degree of H2O2 for enhancing the nanocatalytic‐therapeutic efficacy, which successfully achieves a remarkable synergistic anticancer outcome with minimal side effects. 相似文献
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Anant K. Singh Wentong Lu Dulal Senapati Sadia Afrin Khan Zhen Fan Tapas Senapati Teresa Demeritte Lule Beqa Paresh Chandra Ray 《Small (Weinheim an der Bergstrasse, Germany)》2011,7(17):2517-2525
A recent gold nanotechnology‐driven approach opens up a new possibility for the destruction of cancer cells through photothermal therapy. Ultimately, photothermal therapy may enter into clinical therapy and, as a result, there is an urgent need for techniques to monitor the tumor response to therapy. Driven by this need, a nanoparticle surface‐energy‐transfer (NSET) approach to monitor the photothermal therapy process by measuring a simple fluorescence intensity change is reported. The fluorescence intensity change is due to the light‐controlled photothermal release of single‐stranded DNA/RNA via dehybridization during the therapy process. Time‐dependent results show that just by measuring the fluorescence intensity change, the photothermal therapy response during the therapy process can be monitored. The possible mechanism and operating principle of the NSET assay are discussed. Ultimately, this NSET assay could have enormous potential applications in rapid, on‐site monitoring of the photothermal therapy process, which is critical to providing effective treatment of cancer and multidrug‐resistant bacterial infections. 相似文献
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Weiqiang Chen Steven G. Allen Weiyi Qian Zifeng Peng Shuo Han Xiang Li Yubing Sun Chelsea Fournier Liwei Bao Raymond H. W. Lam Sofia D. Merajver Jianping Fu 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(5)
Cancer stem‐like cells (CSCs) have been shown to initiate tumorigenesis and cancer metastasis in many cancer types. Although identification of CSCs through specific marker expression helps define the CSC compartment, it does not directly provide information on how or why this cancer cell subpopulation is more metastatic or tumorigenic. In this study, the functional and biophysical characteristics of aggressive and lethal inflammatory breast cancer (IBC) CSCs at the single‐cell level are comprehensively profiled using multiple microengineered tools. Distinct functional (cell migration, growth, adhesion, invasion and self‐renewal) and biophysical (cell deformability, adhesion strength and contractility) properties of ALDH+ SUM149 IBC CSCs are found as compared to their ALDH? non‐CSC counterpart, providing biophysical insights into why CSCs has an enhanced propensity to metastasize. It is further shown that the cellular biophysical phenotype can predict and determine IBC cells' tumorigenic ability. SUM149 and SUM159 IBC cells selected and modulated through biophysical attributes—adhesion and stiffness—show characteristics of CSCs in vitro and enhance tumorigenicity in in vivo murine models of primary tumor growth. Overall, the multiparametric cellular biophysical phenotyping and modulation of IBC CSCs yields a new understanding of IBC's metastatic properties and how they might develop and be targeted for therapeutic interventions. 相似文献
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Advances in the field of nanotechnology together with an increase understanding of tumor immunology have paved the way for the development of more personalized cancer immuno‐nanomedicines. Nanovehicles, due to their specific physicochemical properties, are emerging as key translational moieties in tackling tumor‐promoting, M2‐like tumor‐associated macrophages (TAMs). Cancer immuno‐nanomedicines target TAMs primarily by blocking M2‐like TAM survival or affecting their signaling cascades, restricting macrophage recruitment to tumors and re‐educating tumor‐promoting M2‐like TAMs to the tumoricidal, M1‐like phenotype. Here, the TAM effector mechanisms and strategies for targeting TAMs are summarized, followed by a focus on the mechanistic considerations in the development of novel immuno‐nanomedicines. Furthermore, imaging TAMs with nanoparticles so as to forecast a patient's clinical outcome, describing treatment options, and observing therapy responses is also discussed. At present, strategies that target TAMs are being investigated not only at the basic research level but also in early clinical trials. The significance of TAM‐targeting biomaterials is highlighted, with the goal of facilitating future clinical translation. 相似文献
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Yoon‐Tae Kang Emma Purcell Colin Palacios‐Rolston Ting‐Wen Lo Nithya Ramnath Shruti Jolly Sunitha Nagrath 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(47)
Extracellular vesicles (EVs) are emerging as a potential diagnostic test for cancer. Owing to the recent advances in microfluidics, on‐chip EV isolation is showing promise with respect to improved recovery rates, smaller necessary sample volumes, and shorter processing times than ultracentrifugation. Immunoaffinity‐based microfluidic EV isolation using anti‐CD63 is widely used; however, anti‐CD63 is not specific to cancer‐EVs, and some cancers secrete EVs with low expression of CD63. Alternatively, phosphatidylserine (PS), usually expressed in the inner leaflet of the lipid bilayer of the cells, is shown to be expressed on the outer surface of cancer‐associated EVs. A new exosome isolation microfluidic device (newExoChip), conjugated with a PS‐specific protein, to isolate cancer‐associated exosomes from plasma, is presented. The device achieves 90% capture efficiency for cancer cell exosomes compared to 38% for healthy exosomes and isolates 35% more A549‐derived exosomes than an anti‐CD63‐conjugated device. Immobilized exosomes are then easily released using Ca2+ chelation. The recovered exosomes from clinical samples are characterized by electron microscopy and western‐blot analysis, revealing exosomal shapes and exosomal protein expressions. The newExoChip facilitates the isolation of a specific subset of exosomes, allowing the exploration of the undiscovered roles of exosomes in cancer progression and metastasis. 相似文献