Applied Materials Today
·
2019
·
IF 8.013
Ozioma Udochukwu Akakuru,M. Zubair Iqbal,Chuang Liu,Jie Xing,Zhenni Wei,Zhenqi Jiang,Qianlan Fang,Bo Yuan,Elvis Ikechukwu Nosike,Jianbi Xia,Yinhua Jin,Jianjun Zheng,Aiguo Wu
Magnetic resonance imaging (MRI) signal intensities in tissues are usually enhanced by the injection of metal-based contrast agents (CAs) in patients. Some of these metal compounds have been linked to incurable nephrogenic systemic fibrosis and other neurological disorders, leading to their discontinuation. Herein, we report the design, synthesis, and characterization of a self-assembled metal-free CA which is based on an organic nitroxide radical (4-carboxy-TEMPO) compartmentalized in the biocompatible, biodegradable natural polymer, chitosan (CS), alongside folate targeting for in vivo tumor MRI. This extension conceivably heralds a new application for CS-TEMPO, which hitherto was used in macro-sizes as initiators for grafting CS to various polymers. Significantly, the folic acid (FA)-modified metal-free CA (CS-TEMPO-FA; average size ∼113 nm) is substantially benign, with no evidence of acute toxicity; it exhibits desirable pharmacokinetic profile, enhanced stability in highly reducing environments, high nitroxide loading (molecular relaxivity ∼18.56 mM −1 s −1 ), and effective tumor targeting. This latter characteristic ameliorates the non-specific uptake of CAs by normal cells. CS-TEMPO-FA nanoparticles demonstrate commensurate contrast enhancement of the tumor region up to 1 h post-injection when injected into 4T1 tumor-bearing mice, a contrast enhancement capability hitherto unattained by TEMPO-based CAs. This work points to CS-TEMPO-FA as a potential alternative to metal-based CAs as well as an active folate-targeted metal-free CA for long-term longitudinal tumor MRI which ameliorates the otherwise short in vivo lifetimes of typical organic radicals-based CAs.
研究领域:
生物医学工程
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纳米技术
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材料科学
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医学成像
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药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Jiahui Zou,Jianhua He,Xiaobo Wang,Yajie Wang,Chenchen Wu,Mengya Shi,Hulin Jiang,Zimei Wu,Jianping Liu,Wenli Zhang
Despite the tremendous theranostics potential of nano-scale drug delivery system (NDDS) in oncology field, their tumor-targeting efficiency and safety remain major challenges due to their proneness of off-target accumulation through widespread vascular endothelial gaps (up to 1 μm). To address this problem, in this research, micro-sized cellular platelet “ghosts” (PGs, 1.32 μm, platelet without inner granules and coagulation) were employed as carriers to ship hollow gold nanoparticles (HGNs, 58.7 nm), forming a hierarchical biosafe system ( [email protected] ) to reduce normal tissue interception and enhance tumor targeting delivery of HGNs for improved photothermal therapy . PGs were prepared by an optimized “swelling-extrusion-elution” method, HGNs were loaded in PGs ( [email protected] ) through a “hypotonic dialysis” method and the safety and biodistribution of the system was evaluated in vitro and in vivo . In in vitro condition that stimulated the tumoral vessel acidic microenvironment (pH = 6.5), [email protected] were demonstrated with enhanced membrane fluidity through down-regulation of the glycoprotein Ib expressed on the PGs. This change induced a burst release of nano-sized HGNs which were capable to traverse vascular endothelium layer on a tumor-endothelial cell transwell model, whilst the micro-sized PG carriers were intercepted. In comparison to nano-sized platelet membrane-coated carriers ( [email protected] ), [email protected] showed enhanced internalization and cytotoxicity to 4T1 cells. In animal models, [email protected] remarkably prolonged circulation most likely due to the presence of “self-recognition” receptor-CD47 of PGs, and effectively reduced normal tissue interception via the micro-scale size effect. These both contributed to the significantly improved tumor targeting efficiency of HGNs. [email protected] generated the greater antitumor photothermal efficacy alongside safety in the animals compared to [email protected] Collectively, this study demonstrated the potential of the micro-scale PGs equipped with adjusted membrane GP Ib as biosafe vehicles for HGNs or possibly other nanodrugs. The statement of significance Despite the tremendous theranostics potentials, the safety and tumor-targeting efficiency of nano-scale drug delivery systems (NDDS) are compromised by their undesirable accumulation in normal tissues with widespread vascular endothelial gaps, such as many tumor-targeted NDDSs still accumulated much in liver and/or spleen. Herein, we explored a micro-nano biomimetic cascade delivery system to address the above drawbacks. By forming a hierarchical biosafe system, micro-sized platelet “ghost” (PGs, 1.32 μm) was employed as tumor-targeted delivery carrier to transport hollow gold nanoparticles (HGNs, 58.7 nm). It was demonstrated that this micro-size system could maintain platelet membrane structure thus prolong in vivo circulation, while avoiding extravasation into normal tissues. [email protected] could sensitively respond to the acidic microenvironment near tumor vessel via down-regulation of glycoprotein Ib and rapidly release “nano-bullets”-HGNs to further penetrate into the tumor tissues through EPR effect , thus enhancing photothermal efficacy generated by HGNs under NIR irradiation. Collectively, the micro-scaled PGs could be biosafe vehicles for improved tumor-targeted delivery of HGNs or possibly other nanodrugs.
研究领域:
肿瘤学
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纳米技术
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药物递送
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生物医学工程
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治疗诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2022
·Vol. 51
·期 42
·16119-16125
·
IF 4.569
Shengnan Liu,Jiahong Han,Weijin Wang,Yulei Chang,Runlin Wang,Ziwei Wang,Guangzhe Li,Dongxia Zhu,Martin R. Bryce
Photodynamic therapy (PDT) is a promising cancer treatment method. Traditional small-molecule photosensitizers (PSs) suffer from low intersystem crossing (ISC) ability and aggregation-caused quenching (ACQ), which adversely affects the luminous efficiency and singlet oxygen (1O2) yield of PSs in the aggregated state. Ir(III) complexes are promising PSs with long excited-state lifetime, good photophysical and photochemical properties and large Stokes shifts. Aggregation-induced emission (AIE) characteristics could reduce the nonradiative recombination and improve the ISC ability of excited states through the restriction of the intramolecular motions in aggregated states. Accordingly, two AIE-active Ir(III) complexes Ir-1-N+ and Ir-2-N+ were successfully designed and obtained based on Schiff base ligands. Experimental results showed that Ir-1-N+ and Ir-2-N+ have good photophysical properties and the corresponding nanoparticles (NPs) have good water solubility and 1O2 generation ability. Notably, Ir-2-N+ NPs can be efficiently taken up by mouse breast cancer cells (4T1 cells) with good biocompatibility, low dark toxicity and excellent phototoxicity. This work demonstrates a versatile strategy for exploiting efficient transition metal PSs with a cationic ligand in PDT.
研究领域:
化学
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材料科学
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生物医学工程
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Huapan Fang,Linfu Chen,Zheng Deng,Yunxuan Gao,Yang Yang,Qian Chen,Zhuang Liu
Oral administration of protein drugs has always been challenging owing to various intestinal barriers. Herein, we developed an efficient oral protein delivery strategy by using in situ polymerization of zwitterions to encapsulate proteins, which were then loaded into enteric coated capsules for oral feeding. After oral administration of such capsules, the enteric coating would be degraded once the capsule enters the intestine, releasing polyzwitterion/protein nanocomplexes. With the help of polyzwitterion modification, such nanocomplexes were able to pass through the mucus and cellular barriers, likely by the proton-assisted amino acid transporter 1 (PAT1) pathway. Such a polyzwitterion-based protein encapsulation strategy could allow for effective oral delivery of different proteins, including bovine serum albumin (BSA), insulin, and antibodies. Using this strategy, the oral bioavailabilities of insulin and immunoglobin G (IgG) were measured to be as high as 16.9% and 12.5%, respectively. Notably, oral feeding of polyzwitterion/insulin capsules could effectively lower the blood glucose level of diabetic animals (mice, rats, and pigs). Moreover, polyzwitterion/antiprogramed death-1 (αPD-1) capsules were able to induce efficient antitumor immune responses, showing significant tumor inhibition effects toward B16F10- and 4T1-tumor bearing mouse models after oral administration. No significant toxic effect was observed for such oral protein formulations in the treated animals. Our work presents a strategy for the efficient oral delivery of protein drugs, including those with large molecular weights (e.g., antibodies) that can hardly be orally delivered using existing technologies.
研究领域:
药学
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生物技术
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药物递送系统
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蛋白质工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Huihui Liu,Qing Wang,Jingru Guo,Kai Feng,Yiling Ruan,Zhihao Zhang,Xin Ji,Jigang Wang,Tao Zhang,Xiaolian Sun
Cerenkov radiation induced photodynamic therapy (CR-PDT) can tackle the tissue penetration limitation of traditional PDT. However, co-delivery of radionuclides and photosensitizer may cause continuous phototoxicity in normal tissues during the circulation. 5-aminolevulinic acid (ALA) which can intracellularly transform into photosensitive protoporphyrin IX (PpIX) is a cancer-selective photosensitizer with negligible side effect. However, the hydrophilic nature of ALA and the further conversion of PpIX to photoinactive Heme severely hinder the therapeutic benefits of ALA-based PDT. Herein, we developed an 89 Zr-labeled, pH responsive ALA and artemisinin (ART) co-loaded liposome ( 89 Zr-ALA-Liposome-ART) for highly selective cancer therapy. 89 Zr can serve as the internal excitation source to self-activate PpIX for CR-PDT, and the photoinactive Heme can activate the chemotherapeutic effect of ART. The 89 Zr-ALA-Liposome-ART exhibited excellent tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c mice via CR-PDT and chemotherapy. Combined with anti-PD-L1, the 89 Zr-ALA-Liposome-ART elicited strong antitumor immunity to against tumor recurrence.
研究领域:
药学
·
放射肿瘤学
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纳米技术
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免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-20
·
IF 11.3
Fu Shiyao,Wang Mingao,Li Bin,Li Xu,Cheng Jianjun,Zhao Haitian,Zhang Hua,Dong Aijun,Lu Weihong,Yang Xin
Background Multi-component nano-delivery systems based on chemotherapy (chemo)- photodynamic therapy (PDT)- chemodynamic therapy (CDT) have gained increased attention as a promising strategy to improve clinical outcomes in cancer treatment. However, there remains a challenge in developing biodegradable, biocompatible, less toxic, yet highly efficient multicomponent nanobased drug delivery systems (DDS). Here, our study presents the screening and development of a novel DDS based on co-assemblies natural small molecule (NSMs). These molecules (oleanolic acid, and betulinic acid) are combined with photosensitizers Chlorine6 (Ce6) and Cu 2+ that are encapsulated by tumor cell membranes. This nanocarrier encapsulated in tumor cell membranes achieved good tumor targeting and a significant improvement in tumor accumulation. Methods A reprecipitation method was used to prepare the co-assembled nanocarrier, followed by the introduction of Cu 2 + into the DDS (OABACe6 NPs). Then, by wrapping the surface of NPs with the cell membranes of 4T1 which is a kind of mouse breast cancer cells (CM@OABACe6/Cu NPs). and analysis of its structure and size distribution with UV–Vis, XPS, FT-IR, SEM, TEM, and DLS. The synergistic effects of in vitro chemotherapy, CDT and PDT and targeting were also validated by cellular and animal studies. Results It was shown that CM@OABACe6/Cu NPs achieved good tumor targeting and a significant improvement in tumor accumulation. In the composite nano-assembly, the NSMs work together with the Ce6 to provide effective and safe chemo and PDT. Moreover, the effect of reduced PDT due to the depletion of reactive oxygen species (ROS) by excess glutathione (GSH) in the tumor can be counteracted when Cu 2 + is introduced. More importantly, it also confers CDT through a Fenton-like catalytic reaction with H 2 O overexpressed at the tumor site. Conclusions By constructing CM@OABACe6/Cu NPs with homologous targeting, we create a triple synergistic platform for cancer therapy using PDT, chemo, and CDT. We propose here a novel combinatorial strategy for designing more naturally co-assembled small molecules, especially for the development of multifunctional synergistic therapies that utilize NSMs.
研究领域:
纳米技术
·
癌症治疗
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药物递送系统
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Hu Honglei,Zheng Shuting,He Chenxi,Zheng Yinfei,Wei Qiming,Chen Siwen,Wu Zede,Xu Yikai,Zhao Bingxia,Yan Chenggong
Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles “turned on” spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.
研究领域:
癌症研究
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放射肿瘤学
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免疫治疗
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纳米技术
·
分子影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Anyi Dao,Shiyan Chen,Li Pan,Qingyan Ren,Xun Wang,Haorui Wu,Qiufang Gong,Zeduan Chen,Shaomin Ji,Jiaxi Ru,HaoTu Zhu,Chao Liang,Pingyu Zhang,Haiping Xia,Huaiyi Huang
Photoactivable chemotherapy (PACT) using metallic complexes provides spatiotemporal selectivity over drug activation for targeted anticancer therapy. However, the poor absorption in near-infrared (NIR) light region of most metallic complexes renders tissue penetration challenging. Herein, an NIR light triggered dinuclear photoactivable Ru(II) complex ( Ru2 ) is presented and the antitumor mechanism is comprehensively investigated. The introduction of a donor–acceptor–donor (D–A–D) linker greatly enhances the intramolecular charge transition, resulting in a high molar extinction coefficient in the NIR region with an extended triplet excited state lifetime. Most importantly, when activated by 700 nm NIR light, Ru2 exhibits unique slow photodissociation kinetics that facilitates synergistic photosensitization and photocatalytic activity to destroy diverse intracellular biomolecules. In vitro and in vivo experiments show that when activated by 700 nm NIR light, Ru2 exhibits nanomolar photocytotoxicity toward 4T1 cancer cells via the induction of calcium overload and endoplasmic reticulum (ER) stress. These findings provide a robust foundation for the development of NIR-activated Ru(II) PACT complexes for phototherapeutic application.
研究领域:
癌症治疗
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光疗
·
无机化学
·
材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Qi Sun,Zhenzhen Yang,Meng Lin,Yiwei Peng,Rudong Wang,Yitian Du,Yu Zhou,Jiajia Li,Xianrong Qi
Phototherapy and immunogenic cell death (ICD) are powerful strategies to fight cancer. However, their therapeutic outcomes are diminished by immunosuppressive and hypoxia microenvironment . Herein, a photo-based, immunomodulating and hypoxia-alleviated nanosystem , [email protected] , is proposed to achieve the synergism between phototherapy and immunotherapy. Catalase (CAT) and anti-GITR antibody (DTA-1) are loaded to photothermal agent and photosensitizer composed PDA-ICG nanoparticles . The [email protected] exhibits intrinsic local hyperthermia and enhanced ROS generation in tumor, and abrogates tumor immune suppression. It results in reduction of intratumoral FOXP3 + regulatory T cells (4.3-fold) and increase of CD4 + effector T cells (1.5-fold) compare with the control, and promotes damage associated molecular patterns generation to reinvigorate ICD effect. The potent antitumor of [email protected] is proved in 4T1 bilateral tumor-bearing mice, with inhibition ratio of 95.1% for primary cancers and 68.7% for abscopal cancers. Our findings highlight great promise of the constructed versatility nanosystem to fix bottlenecks for cancer therapy.
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Yongli Shi,Xiaofei Pan,Suyue Xu,Huiqing Zhu,Bingqian Zhao,Zeyu Sun,Ruoyi Dong,Na Li,Xueyan Hou,Xue Yang
The purpose of this study was to synthesize DHPD polymers through the conjugation of doxorubicin (DOX) molecules onto poly(ethylene glycol) (PEG) chains via acylhydrazone bonds, and to fabricate pH-responsive DHPD nanoparticles (NPs) for investigation of their biosecurity and in vivo anti-tumor activity. The morphology, size distribution, stability, pH-responsiveness, biosecurity, and in vivo anti-tumor effects of the DHPD NPs were evaluated. Characterization of the DHPD polymers using 1 H NMR, FTIR, and Raman spectra confirmed their successful synthesis. The DHPD NPs exhibited a round morphology with an average diameter of 144.4 ± 1.7 nm and a polydispersity index (PDI) of 0.23 ± 0.02. Biosecurity studies indicated that the DHPD NPs were non-toxic to treated mice, and in vitro cell tests demonstrated their ability to be taken up by 4T1 cells. Under the acidic microenvironment of 4T1 cells, the acylhydrazone bonds were cleaved, resulting in increased DOX delivery to tumor cells and improved in vivo anti-tumor effects. Animal experiments confirmed that the DHPD NPs reduced DOX toxicity while enhancing its anti-tumor activity. Furthermore, results from the analysis of γ-interferon (INF-γ), tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) indicated that the DHPD NPs improved the anti-4T1 tumor effect of DOX, suggesting their potential application in the treatment of breast cancer.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2018
·
IF 4.432
Lixia Yu,Anjie Dong,Ruiwei Guo,Muyang Yang,Liandong Deng,Jianhua Zhang
Chemo-photothermal therapy has shown enormous potential in treating cancer. To achieve the chemo-photothermal synergistic effect, an efficient nanoparticulate system with the ability for simultaneous codelivery of chemotherapeutic drug and photothermal agent as well as photothermal-triggered drug release is highly desirable. Herein, an in situ polymerization within liposome template was designed to prepare liposome-coated poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-co-AAM)) nanogels, which can efficiently coencapsulate a NIR dye indocyanine green (ICG) and high amount of doxorubicin hydrochloride (DOX). The DOX/ICG coloaded hybrid nanogels, denoted as DI-NGs@lipo, integrated the desirable functions of PEGylated liposomes and thermosensitive nanogels. The PEGylated liposome shell provided excellent storage stability, hemodynamic stability, and fluorescence stability. Meanwhile, the thermosensitive P(NIPAM-co-AAM) nanogels core endowed DI-NGs@lipo with volume phase transition temperature (VPTT) at about 40 °C, allowing for thermo-controlled transformation and drug release. The significant photothermal effect of DI-NGs@lipo and the simultaneous hyperthermia-triggered DOX release were observed under NIR light irradiation. The DI-NGs@lipo was demonstrated to be uptaken by 4T1 murine breast cancer cells via endocytosis, enhancing the distribution of DOX in the cell nucleus. Compared with chemo or photothermal treatment alone, the combination treatment of DI-NGs@lipo with NIR light irradiation induced significantly higher cytotoxicity to 4T1 cells, demonstrating the chemo-photothermal synergistic therapeutic effects on tumor cells. In a word, the strategy provided here offers a facile approach to develop a multifunctional nanoplatform for codelivery of DOX and ICG, which can synergistically improve the cancer-cell-killing efficiency, demonstrating great potential in chemo-photothermal therapy.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
光热疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Han Wang,Zhaohui Wang,Yuanbiao Tu,Yongkuan Li,Tian Xu,Man Yang,Peng Wang,Yueqing Gu
Cancer starvation therapy based on catalytic chemistry of glucose oxidase (GOx) offers great potential for multimodal treatment, benefiting from both nutrition shutting-off and the oxidization product hydrogen peroxide (H 2 O 2 ). Herein, further optimization of such combined therapy was achieved by a cascade Nano-reactor, which was constructed by incorporating GOx into a bio-mimic upconversion nanosystem . The cascade began when GOx was delivered into tumor sites through homotypic targeting, facilitating selective starving of cancer cells and H 2 O 2 generation. Then, upon 980 nm laser excitation, the 470 nm light emitted by upconversion nanoparticles (NaYF 4 : Yb, Tm) photolyzed H 2 O 2 into hydroxyl radical for phototherapy, superior to direct photolysis by blue light with limited tissue penetration depth. Meanwhile, the 800 nm emission of UCNPs was used to track the in vivo fate and tumor targeting ability of the Nano-reactor. Radionuclide imaging further confirmed the targeting of the Nano-reactor to subcutaneous 4T1 tumor and lung metastasis. Significantly enhanced therapeutic efficacy of this cascade starvation-phototherapy was validated in vitro and in vivo , suggesting the Nano-reactor as a smart, simple and strong system for cancer multimodal therapy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
光疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）