共查询到20条相似文献,搜索用时 31 毫秒
1.
Yuxin Guo Hao‐Ran Jia Xiaodong Zhang Xinping Zhang Qing Sun Shao‐Zhe Wang Jing Zhao Fu‐Gen Wu 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(31)
Fenton reaction‐mediated chemodynamic therapy (CDT) can kill cancer cells via the conversion of H2O2 to highly toxic HO?. However, problems such as insufficient H2O2 levels in the tumor tissue and low Fenton reaction efficiency severely limit the performance of CDT. Here, the prodrug tirapazamine (TPZ)‐loaded human serum albumin (HSA)–glucose oxidase (GOx) mixture is prepared and modified with a metal–polyphenol network composed of ferric ions (Fe3+) and tannic acid (TA), to obtain a self‐amplified nanoreactor termed HSA–GOx–TPZ–Fe3+–TA (HGTFT) for sustainable and cascade cancer therapy with exogenous H2O2 production and TA‐accelerated Fe3+/Fe2+ conversion. The HGTFT nanoreactor can efficiently convert oxygen into HO? for CDT, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical‐mediated chemotherapy. Besides, it is revealed that the nanoreactor can significantly elevate the intracellular reactive oxygen species content and hypoxia level, decrease the intracellular glutathione content, and release metal ions in the tumors for metal ion interference therapy (also termed “ion‐interference therapy” or “metal ion therapy”). Further, the nanoreactor can also increase the tumor’s hypoxia level and efficiently inhibit tumor growth. It is believed that this tumor microenvironment‐regulable nanoreactor with sustainable and cascade anticancer performance and excellent biosafety represents an advance in nanomedicine. 相似文献
2.
Jian Jiang Na Shen Tianyuan Ci Zhaohui Tang Zhen Gu Gao Li Xuesi Chen 《Advanced materials (Deerfield Beach, Fla.)》2019,31(44)
Tumor‐associated enzyme‐activated prodrugs can potentially improve the selectivity of chemotherapeutics. However, the paucity of tumor‐associated enzymes which are essential for prodrug activation usually limits the antitumor potency. A cooperative strategy that utilizes combretastatin A4 nanodrug (CA4‐NPs) and matrix metalloproteinase 9 (MMP9)‐activated doxorubicin prodrug (MMP9‐DOX‐NPs) is developed. CA4 is a typical vascular disrupting agent that can selectively disrupt immature tumor blood vessels and exacerbate the tumor hypoxia state. After treatment with CA4‐NPs, MMP9 expression can be significantly enhanced by 5.6‐fold in treated tumors, which further boosts tumor‐selective active drug release of MMP9‐DOX‐NPs by 3.7‐fold in an orthotopic 4T1 mammary adenocarcinoma mouse model. The sequential delivery of CA4‐NPs and MMP9‐DOX‐NPs exhibits enhanced antitumor efficacy with reduced systemic toxicity compared with the noncooperative controls. 相似文献
3.
Guosheng Song Liang Cheng Yu Chao Kai Yang Zhuang Liu 《Advanced materials (Deerfield Beach, Fla.)》2017,29(32)
Radiation therapy (RT) including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT) has been widely used for clinical cancer treatment. However, owing to the low radiation absorption of tumors, high doses of ionizing radiations are often needed during RT, leading to severe damages to normal tissues adjacent to tumors. Meanwhile, the RT efficacies are limited by different mechanisms, among which the tumor hypoxia‐associated radiation resistance is a well‐known one, as there exists hypoxia inside most solid tumors while oxygen is essential to enhance radiation‐induced DNA damages. With the development in nanotechnology, there have been great interests in using nanomedicine strategies to enhance radiation responses of tumors. Nanomaterials containing high‐Z elements to absorb radiation rays (e.g. X‐ray) can act as radio‐sensitizers to deposit radiation energy within tumors and promote treatment efficacy. Nanoscale carriers are able to deliver therapeutic radioisotopes into tumors for internal RIT, or chemotherapeutic drugs for synergistically combined chemo‐radiotherapy. As uncovered in recent studies, the tumor microenvironment could be modulated by various nanomedicine approaches to overcome hypoxia‐associated radiation resistance. Herein, the authors will summarize the applications of nanomedicine for RT cancer treatment, and pay particular attention to the latest development of ‘advanced materials' for enhanced cancer RT. 相似文献
4.
Longlong Tian Qian Chen Xuan Yi Jiawen Chen Chao Liang Yu Chao Kai Yang Zhuang Liu 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(25)
Although nanoparticle‐based drug delivery systems have been widely explored for tumor‐targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia‐associated resistance to radiation‐induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide 131I labeled human serum albumin (HSA)‐bound manganese dioxide nanoparticles (131I‐HSA‐MnO2) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME). Such 131I‐HSA‐MnO2 nanoparticles with suitable sizes during blood circulation show rather efficient tumor passive uptake owing to the enhanced permeability and retention effect, as well as little retention in other normal organs to minimize radiotoxicity. The acidic TME can trigger gradual degradation of MnO2 and thus decomposition of 131I‐HSA‐MnO2 nanoparticles into individual 131I‐HSA with sub‐10 nm sizes and greatly improves intratumoral diffusion. Furthermore, oxygen produced by MnO2‐triggered decomposition of tumor endogenous H2O2 would be helpful to relieve hypoxia‐associated RIT resistant for those tumors. As the results, the 131I‐HSA‐MnO2 nanoparticles appear to be a highly effective RIT agent showing great efficacy in tumor treatment upon systemic administration. 相似文献
5.
Dapeng Chen Qing Yu Xuan Huang Hanming Dai Tao Luo Jinjun Shao Peng Chen Jie Chen Wei Huang Xiaochen Dong 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(23)
Hypoxia severely impedes photodynamic therapy (PDT) efficiency. Worse still, considerable tumor metastasis will occur after PDT. Herein, an organic superoxide radical (O2??) nano‐photogenerator as a highly effcient type I photosensitizer with robust vascular‐disrupting efficiency to combat these thorny issues is designed. Boron difluoride dipyrromethene (BODIPY)‐vadimezan conjugate (BDPVDA) is synthesized and enwrapped in electron‐rich polymer‐brushes methoxy‐poly(ethylene glycol)‐b‐poly(2‐(diisopropylamino) ethyl methacrylate) (mPEG‐ PPDA) to afford nanosized hydrophilic type I photosensitizer (PBV NPs). Owing to outstanding core–shell intermolecular electron transfer between BDPVDA and mPEG‐PPDA, remarkable O2?? can be produced by PBV NPs under near‐infrared irradiation even in severe hypoxic environment (2% O2), thus to accomplish effective hypoxic‐tumor elimination. Simultaneously, the efficient ester‐bond hydrolysis of BDPVDA in the acidic tumor microenvironment allows vadimezan release from PBV NPs to disrupt vasculature, facilitating the shut‐down of metastatic pathways. As a result, PBV NPs will not only be powerful in resolving the paradox between traditional type II PDT and hypoxia, but also successfully prevent tumor metastasis after type I PDT treatment (no secondary‐tumors found in 70 days and 100% survival rate), enabling enhancement of existing hypoxic‐and‐metastatic tumor treatment. 相似文献
6.
Engineering Novel Targeted Boron‐10‐Enriched Theranostic Nanomedicine to Combat against Murine Brain Tumors via MR Imaging‐Guided Boron Neutron Capture Therapy
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Naresh Kuthala Raviraj Vankayala Yi‐Nan Li Chi‐Shiun Chiang Kuo Chu Hwang 《Advanced materials (Deerfield Beach, Fla.)》2017,29(31)
Glioblastoma multiforme (GBM) is a very common type of “incurable” malignant brain tumor. Although many treatment options are currently available, most of them eventually fail due to its recurrence. Boron neutron capture therapy (BNCT) emerges as an alternative noninvasive therapeutic treatment modality. The major challenge in treating GBMs using BNCT is to achieve selective imaging, targeting, and sufficient accumulation of boron‐containing drug at the tumor site so that effective destruction of tumor cells can be achieved without harming the normal brain cells. To tackle this challenge, this study demonstrates for the first time that an unprecedented 10B‐enriched (96% 10B enrichment) boron nanoparticle nanomedicine (10BSGRF NPs) surface‐modified with a Fluorescein isothiocyanate (FITC)‐labeled RGD‐K peptide can pass through the brain blood barrier, selectively target at GBM brain tumor sites, and deliver high therapeutic dosage (50.5 µg 10B g?1 cells) of boron atoms to tumor cells with a good tumor‐to‐blood boron ratio of 2.8. The 10BSGRF NPs not only can enhance the contrast of magnetic resonance (MR) imaging to help diagnose the location/size/progress of brain tumor, but also effectively suppress murine brain tumors via MR imaging‐guided BNCT, prolonging the half‐life of mice from 22 d (untreated group) to 39 d. 相似文献
7.
Qian Chen Jiawen Chen Zhijuan Yang Jun Xu Ligeng Xu Chao Liang Xiao Han Zhuang Liu 《Advanced materials (Deerfield Beach, Fla.)》2019,31(10)
External radiotherapy is extensively used in clinic to destruct tumors by locally applied ionizing‐radiation beams. However, the efficacy of radiotherapy is usually limited by tumor hypoxia‐associated radiation resistance. Moreover, as a local treatment technique, radiotherapy can hardly control tumor metastases, the major cause of cancer death. Herein, core–shell nanoparticles based poly(lactic‐co‐glycolic) acid (PLGA) are fabricate, by encapsulating water‐soluble catalase (Cat), an enzyme that can decompose H2O2 to generate O2, inside the inner core, and loading hydrophobic imiquimod (R837), a Toll‐like‐receptor‐7 agonist, within the PLGA shell. The formed PLGA‐R837@Cat nanoparticles can greatly enhance radiotherapy efficacy by relieving the tumor hypoxia and modulating the immune‐suppressive tumor microenvironment. The tumor‐associated antigens generated postradiotherapy‐induced immunogenic cell death in the presence of such R837‐loaded adjuvant nanoparticles will induce strong antitumor immune responses, which together with cytotoxic T‐lymphocyte associated protein 4 (CTLA‐4) checkpoint blockade will be able to effectively inhibit tumor metastases by a strong abscopal effect. Moreover, a long term immunological memory effect to protect mice from tumor rechallenging is observed post such treatment. This work thus presents a unique nanomedicine approach as a next‐generation radiotherapy strategy to enable synergistic whole‐body therapeutic responses after local treatment, greatly promising for clinical translation. 相似文献
8.
Jiawen Chen Chao Liang Xuejiao Song Xuan Yi Kai Yang Liangzhu Feng Zhuang Liu 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(46)
It is hard for current radionuclide therapy to render solid tumors desirable therapeutic efficacy owing to insufficient tumor‐targeted delivery of radionuclides and severe tumor hypoxia. In this study, a biocompatible hybrid protein nanoreactor composed of human serum albumin (HSA) and catalase (CAT) molecules is constructed via glutaraldehyde‐mediated crosslinking. The obtained HSA‐CAT nanoreactors (NRs) show retained and well‐protected enzyme stability in catalyzing the decomposition of H2O2 and enable efficient labeling of therapeutic radionuclide iodine‐131 (131I). Then, it is uncovered that such HSA‐CAT NRs after being intravenously injected into tumor‐bearing mice exhibit efficient passive tumor accumulation as vividly visualized under the fluorescence imaging system and gamma camera. As the result, such HSA‐CAT NRs upon tumor accumulation would significantly attenuate tumor hypoxia by decomposing endogenous H2O2 produced by cancer cells to molecular oxygen, and thereby remarkably improve the therapeutic efficacy of radionuclide 131I. This study highlights the concise preparation of biocompatible protein nanoreactors with efficient tumor homing and hypoxia attenuation capacities, thus enabling greatly improved tumor radionuclide therapy with promising potential for future clinical translation. 相似文献
9.
Funeng Xu Xuehui Huang Yi Wang Shaobing Zhou 《Advanced materials (Deerfield Beach, Fla.)》2020,32(16):1906745
The complex tumor microenvironment constitutes a variety of barriers to prevent nanoparticles (NPs) delivery and results in extremely low accumulation of nanomedicines in solid tumors. Here, a newly developed size-changeable collagenase-modified polymer micelle is employed to enhance the penetration and retention of nanomedicine in deep tumor tissue. The TCPPB micelle is first formed by self-assembly of maleimide-terminated poly(ethylene glycol)-block-poly(β-amino ester) (MAL-PEG-PBAE) and succinic anhydride-modified cisplatin-conjugated poly(ε-caprolactone)-block-poly(ethylene oxide)-triphenylphosphonium (CDDP-PCL-PEO-TPP). Next, Col-TCPPB NPs are prepared through a “click” chemical combination of thiolated collagenase and maleimide groups on TCPPB micelle. Finally, biocompatible chondroitin sulfate (CS) is coated to obtain CS/Col-TCPPB NPs for avoiding collagenase inactivation in blood circulation. In tumor acidic microenvironment, the hydrophobic PBAE segments of the resultant micelles become hydrophilic, leading to a dissociation and subsequent dissolution of partial collagenase-containing components (Col-PEG-PBAE) from NPs. The dissolved Col-PEG-PBAE promotes the digestion of collagen fibers in tumor tissue like a scavenger, which enhances the NPs penetration. Simultaneously, the increased hydrophilicity of residual Col-PEG-PBAE in the micellar matrix causes an expansion of the NPs, resulting in an enhanced intratumoral retention. In tumor cells, the NPs target to release the cisplatin drugs into mitochondria, achieving an excellent anticancer efficacy. 相似文献
10.
Phototherapy is a promising treatment method for cancer therapy. However, the various factors have greatly restricted phototherapy development, including the poor accumulation of photosensitizer in tumor, hypoxia in solid tumor tissue and systemic phototoxicity. Herein, a mitochondrial‐targeted multifunctional dye‐anchored manganese oxide nanoparticle (IR808@MnO NP) is developed for enhancing phototherapy of cancer. In this nanoplatform, IR808 as a small molecule dye acts as a tumor targeting ligand to make IR808@MnO NPs with capacity to actively target tumor cells and relocate finally in the mitochondria. Meanwhile, continuous production of oxygen (O2) and regulation of pH induced by the high reactivity and specificity of MnO NPs toward mitochondrial endogenous hydrogen peroxide (H2O2) could effectively modulate tumor hypoxia and lessen the tumor subacid environment. Large amounts of reactive oxide species (ROS) are generated during the reaction process between H2O2 and MnO NPs. Furthermore, under laser irradiation, IR808 in IR808@MnO NPs turns O2 into a highly toxic singlet oxygen (1O2) and generates hyperthermia. The results indicate that IR808@MnO NPs have the high efficiency of specific targeting of tumors, relieving tumor subacid environment, improving the tumor hypoxia environment, and generating large amounts of ROS to kill tumor cells. It is expected to have a wide application in treating cancer. 相似文献
11.
Yue Zheng Yuyi Ling Dong-Yang Zhang Cai-Ping Tan Hang Zhang Gang-Gang Yang Hongsheng Wang Liang-Nian Ji Zong-Wan Mao 《Small (Weinheim an der Bergstrasse, Germany)》2021,17(1):2005086
The epigenetic dysregulation and hypoxia are two important factors that drive tumor malignancy, and N6-methyladenosine (m6A) in mRNA is involved in the regulation of gene expression. Herein, a nanocatalyst OsSx-PEG (PEG = poly(ethylene glycol)) nanoparticles (NPs) as O2 modulator is developed to improve tumor hypoxia. OsSx-PEG NPs can significantly downregulate genes involved in hypoxia pathway. Interestingly, OsSx-PEG NPs elevate RNA m6A methylation levels to cause the m6A-dependent mRNA degradation of the hypoxia-related genes. Moreover, OsSx-PEG NPs can regulate the expression of RNA m6A methyltransferases and demethylases. Finally, DOX@OsSx-PEG ( DOX = doxorubicin; utilized as a model drug) NPs modulate tumor hypoxia and regulate mRNA m6A methylation of hypoxia-related genes in vivo. As the first report about relationship between catalytic nanomaterials and RNA modifications, the research opens a new avenue for unveiling the underlying action mechanisms of hypoxia-modulating nanomaterials and shows potential of regulating RNA modification to overcome chemoresistance. 相似文献
12.
Zhimei He Yunlu Dai Xiangli Li Dan Guo Yijing Liu Xiaolin Huang Jingjing Jiang Sheng Wang Guizhi Zhu Fuwu Zhang Lisen Lin Jun‐Jie Zhu Guocan Yu Xiaoyuan Chen 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(4)
During photodynamic therapy (PDT), severe hypoxia often occurs as an undesirable limitation of PDT owing to the O2‐consuming photodynamic process, compromising the effectiveness of PDT. To overcome this problem, several strategies aiming to improve tumor oxygenation are developed. Unlike these traditional approaches, an opposite method combining hypoxia‐activated prodrug and PDT may provide a promising strategy for cancer synergistic therapy. In light of this, azido‐/photosensitizer‐terminated UiO‐66 nanoscale metal–organic frameworks (UiO‐66‐H/N3 NMOFs) which serve as nanocarriers for the bioreductive prodrug banoxantrone (AQ4N) are engineered. Owing to the effective shielding of the nanoparticles, the stability of AQ4N is well preserved, highlighting the vital function of the nanocarriers. By virtue of strain‐promoted azide–alkyne cycloaddition, the nanocarriers are further decorated with a dense PEG layer to enhance their dispersion in the physiological environment and improve their therapeutic performance. Both in vitro and in vivo studies reveal that the O2‐depleting PDT process indeed aggravates intracellular/tumor hypoxia that activates the cytotoxicity of AQ4N through a cascade process, consequently achieving PDT‐induced and hypoxia‐activated synergistic therapy. Benefiting from the localized therapeutic effect of PDT and hypoxia‐activated cytotoxicity of AQ4N, this hybrid nanomedicine exhibits enhanced therapeutic efficacy with negligible systemic toxicity, making it a promising candidate for cancer therapy. 相似文献
13.
Zhouqi Meng Xuanfang Zhou Jun Xu Xiao Han Ziliang Dong Hairong Wang Yaojia Zhang Jialin She Ligeng Xu Chao Wang Zhuang Liu 《Advanced materials (Deerfield Beach, Fla.)》2019,31(24)
Photodynamic therapy (PDT) has shown the potential of triggering systemic antitumor immune responses. However, while the oxygen‐deficient hypoxic tumor microenvironment is a factor that limits the PDT efficacy, the immune responses after conventional PDT usually are not strong enough to eliminate metastatic tumors. Herein, a light‐triggered in situ gelation system containing photosensitizer‐modified catalase together with poly(ethylene glycol) double acrylate (PEGDA) as the polymeric matrix is designed. Immune adjuvant nanoparticles are further introduced into this system to trigger robust antitumor immune responses after PDT. Following local injection of the mixed precursor solution into tumors and the subsequent light exposure, polymerization of PEGDA can be initiated to induce in situ gelation. Such hybrid hydrogel with long‐term tumor retention of various agents and the ability to enable persistent tumor hypoxia relief can enable multiple rounds of PDT, which results in significantly enhanced immune responses by multiround stimulation. Further combination of such gel‐based multiround PDT with anticytotoxic T‐lymphocyte antigen‐4 checkpoint blockade offers not only the abscopal effect to inhibit growth of distant tumors but also effective long‐term immune memory protection from rechallenged tumors. Therefore, such a light‐triggered in situ gelation system by a single‐dose injection can enable greatly enhanced photoimmunotherapy by means of repeated stimulations. 相似文献
14.
Erythrocyte‐Membrane‐Enveloped Perfluorocarbon as Nanoscale Artificial Red Blood Cells to Relieve Tumor Hypoxia and Enhance Cancer Radiotherapy
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Min Gao Chao Liang Xuejiao Song Qian Chen Qiutong Jin Chao Wang Zhuang Liu 《Advanced materials (Deerfield Beach, Fla.)》2017,29(35)
Hypoxia, a common feature within many types of solid tumors, is known to be closely associated with limited efficacy for cancer therapies, including radiotherapy (RT) in which oxygen is essential to promote radiation‐induced cell damage. Here, an artificial nanoscale red‐blood‐cell system is designed by encapsulating perfluorocarbon (PFC), a commonly used artificial blood substitute, within biocompatible poly(d ,l ‐lactide‐co‐glycolide) (PLGA), obtaining PFC@PLGA nanoparticles, which are further coated with a red‐blood‐cell membrane (RBCM). The developed PFC@PLGA‐RBCM nanoparticles with the PFC core show rather efficient loading of oxygen, as well as greatly prolonged blood circulation time owing to the coating of RBCM. With significantly improved extravascular diffusion within the tumor mass, owing to their much smaller nanoscale sizes compared to native RBCs with micrometer sizes, PFC@PLGA‐RBCM nanoparticles are able to effectively deliver oxygen into tumors after intravenous injection, leading to greatly relieved tumor hypoxia and thus remarkably enhanced treatment efficacy during RT. This work thus presents a unique type of nanoscale RBC mimic for efficient oxygen delivery into solid tumors, favorable for cancer treatment by RT, and potentially other types of therapy as well. 相似文献
15.
Junlong Geng Chunyang Sun Jie Liu Lun‐De Liao Youyong Yuan Nitish Thakor Jun Wang Bin Liu 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(13):1603-1610
Conjugated polymers (CPs) with strong near‐infrared (NIR) absorption and high heat conversion efficiency have emerged as a new generation of photothermal therapy (PTT) agents for cancer therapy. An efficient strategy to design NIR absorbing CPs with good water dispersibility is essential to achieve excellent therapeutic effect. In this work, poly[9,9‐bis(4‐(2‐ethylhexyl)phenyl)fluorene‐alt‐co‐6,7‐bis(4‐(hexyloxy)phenyl)‐4,9‐di(thiophen‐2‐yl)‐thiadiazoloquinoxaline] (PFTTQ) is synthesized through the combination of donor–acceptor moieties by Suzuki polymerization. PFTTQ nanoparticles (NPs) are fabricated through a precipitation approach using 1,2‐distearoyl‐ sn ‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000] (DSPE‐PEG2000) as the encapsulation matrix. Due to the large NIR absorption coefficient (3.6 L g‐1 cm‐1), the temperature of PFTTQ NP suspension (0.5 mg/mL) could be rapidly increased to more than 50 °C upon continuous 808 nm laser irradiation (0.75 W/cm2) for 5 min. The PFTTQ NPs show good biocompatibility to both MDA‐MB‐231 cells and Hela cells at 400 μg/mL of NPs, while upon laser irradiation, effective cancer cell killing is observed at a NP concentration of 50 μg/mL. Moreover, PFTTQ NPs could efficiently ablate tumor in in vivo study using a Hela tumor mouse model. Considering the large amount of NIR absorbing CPs available, the general encapsulation strategy will enable the development of more efficient PTT agents for cancer or tumor therapy. 相似文献
16.
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
17.
Rui Zhang Zhiyan Zhu Hongying Lv Futian Li Shuqing Sun Juan Li Chun‐Sing Lee 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(49)
Targeting programmed cell death protein 1 (PD‐1)/programmed death ligand 1 (PD‐L1) immunologic checkpoint blockade with monoclonal antibodies has achieved recent clinical success in antitumor therapy. However, therapeutic antibodies exhibit several issues such as limited tumor penetration, immunogenicity, and costly production. Here, Bristol‐Myers Squibb nanoparticles (NPs) are prepared using a reprecipitation method. The NPs have advantages including passive targeting, hydrophilic and nontoxic features, and a 100% drug loading rate. BMS‐202 is a small‐molecule inhibitor of the PD‐1/PD‐L1 interaction that is developed by BMS. Transfer of BMS‐202 NPs to 4T1 tumor‐bearing mice results in markedly slower tumor growth to the same degree as treatment with anti‐PD‐L1 monoclonal antibody (α‐PD‐L1). Consistently, the combination of Ce6 NPs with BMS‐202 NPs or α‐PD‐L1 in parallel shows more efficacious antitumor and antimetastatic effects, accompanied by enhanced dendritic cell maturation and infiltration of antigen‐specific T cells into the tumors. Thus, inhibition rates of primary and distant tumors reach >90%. In addition, BMS‐202 NPs are able to attack spreading metastatic lung tumors and offer immune‐memory protection to prevent tumor relapse. These results indicate that BMS‐202 NPs possess effects similar to α‐PD‐L1 in the therapies of 4T1 tumors. Therefore, this work reveals the possibility of replacing the antibody used in immunotherapy for tumors with BMS‐202 NPs. 相似文献
18.
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
19.
Near‐Infrared Upconversion Mesoporous Cerium Oxide Hollow Biophotocatalyst for Concurrent pH‐/H2O2‐Responsive O2‐Evolving Synergetic Cancer Therapy
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Chi Yao Wenxing Wang Peiyuan Wang Mengyao Zhao Xiaomin Li Fan Zhang 《Advanced materials (Deerfield Beach, Fla.)》2018,30(7)
Tumor hypoxia is typically presented in the central region of solid tumors, which is mainly caused by an inadequate blood flow and oxygen supply. In the conventional treatment of hypoxic human tumors, not only the oxygen‐dependent photodynamic therapy (PDT), but also antitumor drug‐based chemotherapy, is considerably limited. The use of direct oxygen delivering approach with oxygen‐dependent PDT or chemotherapy may potentiate the reactive oxygen species (ROS)‐mediated cytotoxicity of the drug toward normal tissues. Herein, a synergetic one‐for‐all mesoporous cerium oxide upconversion biophotocatalyst is developed to achieve intratumorally endogenous H2O2‐responsive self‐sufficiency of O2 and near‐infrared light controlled PDT simultaneously for overcoming hypoxia cancer. Furthermore, the sufficient O2 plays an important role in overcoming the chemotherapeutic drug‐resistant cancer caused by hypoxia, therefore inducing tumor cell apoptosis significantly. 相似文献
20.
Manganese Dioxide Coated WS2@Fe3O4/sSiO2 Nanocomposites for pH‐Responsive MR Imaging and Oxygen‐Elevated Synergetic Therapy
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Guangbao Yang Rui Zhang Chao Liang He Zhao Xuan Yi Sida Shen Kai Yang Liang Cheng Zhuang Liu 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(2)
Recently, the development of multifunctional theranostic nanoplatforms to realize tumor‐specific imaging and enhanced cancer therapy via responding or modulating the tumor microenvironment (TME) has attracted tremendous interests in the field of nanomedicine. Herein, tungsten disulfide (WS2) nanoflakes with their surface adsorbed with iron oxide nanoparticles (IONPs) via self‐assembly are coated with silica and then subsequently with manganese dioxide (MnO2), on to which polyethylene glycol (PEG) is attached. The obtained WS2‐IO/S@MO‐PEG appears to be highly sensitive to pH, enabling tumor pH‐responsive magnetic resonance imaging with IONPs as the pH‐inert T2 contrast probe and MnO2 as the pH‐sensitive T1 contrast probe. Meanwhile, synergistic combination tumor therapy is realized with such WS2‐IO/S@MO‐PEG, by utilizing the strong near‐infrared light and X‐ray absorbance of WS2 for photothermal therapy (PTT) and enhanced cancer radiotherapy (RT), respectively, as well as the ability of MnO2 to decompose tumor endogenous H2O2 and relieve tumor hypoxia to further overcome hypoxia‐associated radiotherapy resistance. The combination of PTT and RT with WS2‐IO/S@MO‐PEG results in a remarkable synergistic effect to destruct tumors. This work highlights the promise of developing multifunction nanocomposites for TME‐specific imaging and TME modulation, aiming at precision cancer synergistic treatment. 相似文献