Materials Science & Engineering C-Materials for Biological Applications
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2018
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IF 5.08
Guan-Hai Wang,Hua Chen,Yin-Yu Cai,Li Li,Hui-Kang Yang,Qin Li,Zhi-Jiang He,Jian-Tao Lin
The nucleus is one of the most important cellular organelles, where gene encode and transcribe at that location. However, nucleus-targeting gene delivery are rare been reported. It is important to develop a high-efficiency nucleus-targeting gene vector that can deliver targeted gene into nucleus directly for destroy of cancer cells. Here, special nucleus-targeting and size changeable deliver system based on TAT-SS-PAMAM-D3 with TAT functional on the surface and disulfide linked between D2 and D3 is designed to perform highly efficient nucleus-targeting gene delivery for effective cancer cell killing in vitro. CLSM observations reveal that more TAT-SS-PAMAM-D3 are enter into the nucleus when compare to SS-PAMAM-D3. The TAT modified vector can also act as gene deliver to reach high gene transfection efficiencies, high apoptosis and low viability in HeLa cells. This TAT functionalized and disulfide linking in the carrier may become a prospective vector for cancer gene treatment and also offered a different strategy for designing a better gene delivery system.
研究领域:
遗传学
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肿瘤学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Xiaozheng Zhao,Xiao Yang,Xudong Wang,Xiao Zhao,Yinlong Zhang,Shaoli Liu,Gregory J. Anderson,Seong-jin Kim,Yiye Li,Guangjun Nie
Pancreatic ductal adenocarcinoma (PDAC) cells are surrounded by a dense extracellular matrix (ECM), which greatly restricts the access of therapeutic agents, resulting in poor clinical response to chemotherapy. Transforming growth factor-β1 (TGF-β1) signaling plays a crucial role in construction of the desmoplastic stroma and provides potential targets for PDAC therapy. To surmount the pathological obstacle, we developed a size switchable nanosystem based on PEG–PLGA nanospheres encapsulated within liposomes for the combined delivery of vactosertib (VAC), a TGF-β1 receptor kinase inhibitor, and the cytotoxic drug paclitaxel (TAX). By surface modification of the liposomes with a peptide, APTEDB, the nanosystem can be anchored to abundant tumor-associated fibronectin in PDAC stroma and decreases its size by releasing encapsulated TAX-loaded nanospheres, as well as VAC after collapse of the liposomes. The inhibition of ECM hyperplasia by VAC allows TAX more ready access to the cancer cells in addition to its small size, thereby shrinking pancreatic tumor xenografts more effectively than a combination of the free drugs. This size switchable nanosystem enables sequential delivery of drugs at a fixed dose combination with simplified administration and provides an encouraging cascade approach of drug penetration for enhanced chemotherapy in cancers with a dense desmoplastic stroma.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Rui Liu,Wei Xiao,Chuan Hu,Rou Xie,Huile Gao
The size of nanoparticles plays a key role in utilizing enhanced permeability and retention (EPR) effect of tumor, where large-sized nanoparticles possess good retention but poor penetration, while small-sized nanoparticles are on the contrary. Although size-reducible nanoparticles have been designed to partially overcome this dilemma, the initial size and complicated tumor microenvironment remain restricting the tumor distribution of nanoparticles. Herein, we employed tumor-specific CD44 targeted, hyaluronidase-degradable hyaluronic acid (HA) and small-sized, renal-clearable, red emission, cationic bovine serum albumin-protected gold nanocluster ( [email protected] ) to successfully construct size-reducible nanoplatform ( [email protected] @HA). By changing the ratio of HA and [email protected] , different initial sizes of [email protected] @HA were prepared and their tumor targeting efficiencies, pharmacokinetic profiles were evaluated. Then 200 nm of [email protected] @HA with optimal EPR effect was screened out to further load paclitaxel (PTX) and indocyanine green (ICG) for chemo- photothermal therapy and nitric oxide (NO) for modulating tumor microenvironment and enhancing drug delivery. The [email protected] @HA-NO 3 showed size-reducible ability under triggering by hyaluronidase and high accumulation in breast cancer with homogenous intra-tumor distribution, suppressed 95.3% of in-situ tumor growth and inhibited 88.4% of lung metastasis growth. In conclusion, we provide a strategy that fully satisfied the concerns in drug delivery to tumor for improved antitumor effect.
研究领域:
纳米医学
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癌症治疗
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药代动力学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
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2022
·Vol. 49
·期 8
·2655-2667
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IF 10.057
Hou Zhenyu,Zhou Mei,Ma Yuanyuan,Xu Xiaoxuan,Zhang Zhiqi,Lai Shiwei,Fan Wenpei,Xie Jinbing,Ju Shenghong
Purpose Radiation therapy (RT) and photodynamic therapy (PDT) are promising while challenging in treating tumors. The potential radiation resistance of tumor cells and side effects to healthy tissues restrict their clinical treatment efficacy. Effective delivery of therapeutic agents to the deep tumor tissues would be available for tumor-accurate therapy and promising for the tumor therapy. Thus, developing nanoprobes with effectively delivering radiotherapy sensitizers and photosensitizers to the interior of tumors is needed for the accurate combined RT and PDT of tumor. Methods The size-changeable nanoprobes of Gd 2 O 3 @BSA-BSA-Ce6 (BGBC) were synthesized with a crosslinking method. Magnetic resonance imaging (MRI) and in vivo near-infrared (NIR) imaging were measured to evaluate the nanoprobes’ tumor accumulation and intratumor penetration effect. The tumor suppression effect of combined RT and PDT with these nanoprobes was also studied for the 4T1 bearing Balb/c mice. Results The nanoprobes BGBC showed high tumor accumulation and disintegrated into small particles responding to the photo-irradiation-produced reactive oxygen species (ROS), allowing for tumor penetration. Abundant radiotherapy sensitizers and photosensitizers were delivered to the deep tumor tissues, which is available for the accurate therapy of tumor. In addition, the BGBC displayed outstanding MRI and fluorescence imaging effects for evaluating the biodistribution and tumor suppression effect of nanoprobes. Consequently, significant tumor suppression effect was obtained based on the accurate tumor treatment with the combined RT and PDT. Conclusion The designed size-changeable nanoprobes BGBC showed excellent tumor accumulation and deep tumor penetration, resulting in a significant tumor suppression effect based on the combined RT and PDT. This study provides a novel strategy for dual delivery of radiotherapy sensitizers and photosensitizers into the deep tumor tissues and is promising for the accurate theranostics of tumor.
研究领域:
癌症治疗
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放射医学
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纳米医学
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医学影像
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Siqi Ma,Zhaoqing Cong,Jiaxing Wei,Weiya Chen,Di Ge,Feifei Yang,Yonghong Liao
Very little is currently known about how inhaled nanomedicine for lung cancer treatment overcomes biological barriers hampering the tumor availability of drug and nanoparticles . Here, we developed a size-transformable nanocarrier (~ 119 nm) in which small-size nanoparticles (~ 28 nm) were loaded in the large nanocarrier after the addition of modified hyaluronan and could be released upon size-transformation at tumor tissue. Subsequently, the pulmonary and tumor pharmacokinetics of the two nanocarriers containing 7-ethyl-10-hydroxycamptothecin (SN38) and a covalently linked fluorescent sonosensitizer were comparatively investigated after intratracheal instillation to mice bearing orthotopic Lewis lung carcinoma tumors. The results showed that both instilled nanoparticles seemed to transport drug to tumor by direct access and transcytosis of nanoparticles, and diffusion of the released drug with the latter accounting for a great proportion of the drug tumor bioavailability. Relative to the small-size nanocarrier, the size-transformable counterpart appeared to restrict the mucociliary and absorption clearances from the lung and the clearance from the tumor interstitium to circulation, leading to increases in lung and tumor bioavailability of SN38 by 58.5% and 199%, respectively. In addition, the size-transformable nanoformulation conferred deep tumor penetration and sustained levels of both sonosensitizer and SN38 within tumors and simultaneously exerted sonodynamic- and chemo-therapies. Overall, the pulmonary delivery of size-transformable nanocarrier could co-deliver sonosensitizer and drug to deep tumor sites with enhanced tumor accumulation to realize combination therapy in lung cancer.
研究领域:
纳米医学
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癌症治疗
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
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2024
·
IF 3.9
Linrong Shi,Mingzhi Zhu,Ruimin Long,Shibin Wang,Pei Wang,Yuangang Liu
In recent years, there has been growing interest in size-transformable nanoplatforms that exhibit active responses to acidic microenvironments, presenting promising prospects in the field of nanomedicine for tumor therapy. However, the design and fabrication of such size-adjustable nanotherapeutics pose significant challenges compared to size-fixed nanocomposites, primarily due to their distinct pH-responsive requirements. In this study, we developed pH-activated-aggregating nanosystems to integrate chemotherapy and photothermal therapy by creating size-transformable nanoparticles based on Prussian blue nanoparticles (PB NPs) anchored with acid-responsive polyoxometalates (POMs) quantum dots via electrostatic interactions (PPP NPs). Subsequently, we utilized doxorubicin (DOX) as a representative drug to formulate PPPD NPs. Notably, PPPD NPs exhibited a significant response to acidic conditions, resulting in changes in surface charge and rapid aggregation of PPP NPs. Furthermore, the aggregated PPP NPs demonstrated excellent photothermal properties under near-infrared laser irradiation. Importantly, PPPD NPs prolonged their retention time in tumor cells via a size-transformation approach. In vitro cellular assays revealed that the anticancer efficacy of PPPD NPs was significantly enhanced. The IC50 values for the PPPD NPs groupand the PPPD NPs + NIR group were 50.11 μg/mL and 30.9 μg/mL. Overall, this study introduces a novel strategy for cancer therapy, by developing size-aggregating nano-drugs with stimuli-responsive properties, holding promise for improved therapeutic outcomes in future combination approaches involving photothermal therapy and chemotherapy.
研究领域:
纳米医学
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癌症治疗
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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
ACS Applied Materials & Interfaces
·
2017
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IF 7.504
Min Han,Ming-Yi Huang-Fu,Wang-Wei Guo,Ning-Ning Guo,JieJian Chen,Hui-Na Liu,Zhi-Qi Xie,Meng-Ting Lin,Qi-Chun Wei,Jian-Qing Gao
Currently, the limited penetration of nanoparticles remains a major challenge for antitumor nanomedicine to penetrate into the tumor tissues. Herein, we propose a size-shrinkable drug delivery system based on a polysaccharide-modified dendrimer with tumor microenvironment responsiveness for the first time to our knowledge, which was formed by conjugating the terminal glucose of hyaluronic acid (HA) to the superficial amidogen of poly(amidoamine) (PAMAM), using a matrix metalloproteinase-2 (MMP-2)-cleavable peptide (PLGLAG) via click reaction. These nanoparticles had an initial size of ∼200 nm, but once deposited in the presence of MMP-2, they experienced a dramatic and fast size change and dissociated into their dendrimer building blocks (∼10 nm in diameter) because of cleavage of PLGLAG. This rapid size-shrinking characteristic not only promoted nanoparticle extravasation and accumulation in tumors benefited from the enhanced permeability and retention effect but also achieved faster nanoparticle diffusion and penetration. We have further conducted comparative studies of MMP-2-sensitive macromolecules (HA-pep-PAMAM) and MMP-2-insensitive macromolecules (HA–PAMAM) synthesized with a similar particle size, surface charge, and chemical composition and evaluated in both monolayer cells and multicellular spheroids. The results confirmed that the enzyme-responsive size shrink is an implementable strategy to enhance drug penetration and to improve therapeutic efficacy. Meanwhile, macromolecule-based nanoparticles with size-variable characteristics not only promote drug penetration, but they can also be used as gene delivery systems, suggesting great potential as nano-delivery systems.
研究领域:
纳米医学
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癌症治疗
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药物递送系统
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生物材料
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肿瘤微环境工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Jianhua He,Wenli Zhang,Xiaoju Zhou,Fengfei Xu,Jiahui Zou,Qiqi Zhang,Yi Zhao,Hongliang He,Hu Yang,Jianping Liu
Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis; however, the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells. Here, we report reactive oxygen species (ROS)-responsive and size-reducible nanoassemblies, formed by multivalent host-guest interactions between β-cyclodextrins (β-CD)-anchored discoidal recombinant high-density lipoprotein (NP 3 ST ) and hyaluronic acid-ferrocene (HA-Fc) conjugates. The HA-Fc/NP 3 ST nanoassemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP 3 ST , allowing for further plaque penetration, macrophage-targeted cholesterol efflux and drug delivery. In vivo pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP 3 ST reduces plaque size by 53%, plaque lipid deposition by 63%, plaque macrophage content by 62% and local inflammatory factor level by 64% compared to the saline group. Meanwhile, HA-Fc/NP 3 ST alleviates systemic inflammation characterized by reduced serum inflammatory factor levels. Collectively, HA-Fc/NP 3 ST nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability, thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.
研究领域:
纳米技术
·
药学
·
心血管疾病
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Hui Wang,Jianfei Li,Jingbo Xu,Yunfeng Hu,Yifan Zuo,Jin Li
Combination therapy is emerging as a critical strategy in the pursuit of synergistic effects in cancer treatment due to the complicated pathogenesis and rapid progression of tumors. However, the limited tumor accumulation and penetration of nanomedicines within tumors are increasingly recognized as significant barriers to achieving the expected efficacy due to the complex physiological barriers of a solid tumor microenvironment. A size-shrinkable multistage nanocomposite CuS-DOX@MA/Gel was successfully fabricated by conjugating doxorubicin (DOX) onto copper sulfide nanoparticles (CuS NPs) through an imine bond (CuS-DOX), which endowed the system with pH-triggered cargo release. Subsequently, a capping layer composed of metalloproteinase-2 (MMP-2) degradable gelatin and autophagy inhibitor 3-methyladenine (3-MA) was grafted onto CuS-DOX through glutaraldehyde-mediated cross-linking. The size of CuS-DOX@MA/Gel can be effectively reduced from the initial 180.1 nm to small-sized CuS NPs of about 57.2 nm in response to MMP-2. This process of reducing particle size not only facilitated effective retention around the tumor periphery but also significantly enhanced deep penetration into both multicellular spheroids and solid tumors. Simultaneously, the MMP-2-dependent release of 3-MA could block autophagosome formation and augment the sensitivity of chemotherapy. Then, pH sensitivity was confirmed, and CuS-DOX@MA/Gel exhibited proficient drug release in vitro upon exposure to acidic conditions. CuS NPs exhibited the capacity to absorb near-infrared (NIR) light, thereby enabling a sophisticated photodynamic and photothermal therapy that synergistically enhanced chemotherapy. In vivo results demonstrated that CuS-DOX@MA/Gel treated with intravenous administration and an 808 nm laser irradiation achieved excellent tumor inhibition efficacy on 4T1 tumor-bearing mice. This size-adjustable multifunctional strategy should be a potential candidate in the anticancer field due to the outstanding synergistic therapeutic effect.
研究领域:
癌症治疗
·
纳米技术
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药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）