BIOMACROMOLECULES
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2012
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IF 5.479
Xiaojun Cai,Chunyan Dong,Haiqing Dong,Gangmin Wang,Giovanni M. Pauletti,Xiaojing Pan,Huiyun Wen,Isaac Mehl,Yongyong Li,Donglu Shi
A dual stimulus-responsive mPEG-SS-PLL15-glutaraldehyde star (mPEG-SS-PLL15-star) catiomer is developed and biologically evaluated. The catiomer system combines redox-sensitive removal of an external PEG shell with acid-induced escape from the endosomal compartment. The design rationale for PEG shell removal is to augment intracellular uptake of mPEG-SS-PLL15-star/DNA complexes in the presence of tumor-relevant glutathione (GSH) concentration, while the acid-induced dissociation is to accelerate the release of genetic payload following successful internalization into targeted cells. Size alterations of complexes in the presence of 10 mM GSH suggest stimulus-induced shedding of external PEG layers under redox conditions that intracellularly present in the tumor microenvironment. Dynamic laser light scattering experiments under endosomal pH conditions show rapid destabilization of mPEG-SS-PLL15-star/DNA complexes that is followed by facilitating efficient release of encapsulated DNA, as demonstrated by agarose gel electrophoresis. Biological efficacy assessment using pEGFP-C1 plasmid DNA encoding green fluorescence protein and pGL-3 plasmid DNA encoding luciferase as reporter genes indicate comparable transfection efficiency of 293T cells of the catiomer with a conventional polyethyleneimine (bPEI-25k)-based gene delivery system. These experimental results show that mPEG-SS-PLL15-star represents a promising design for future nonviral gene delivery applications with high DNA binding ability, low cytotoxicity, and high transfection efficiency.
研究领域:
生物医学工程
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分子生物学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2021
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IF 12.479
Xianqi Zhu,Lin Li,Jin Tang,Chunyu Yang,Hao Yu,Kunpeng Liu,Ziyan Zheng,Xinggui Gu,Qingsong Yu,Fu-Jian Xu,Zhihua Gan
Metastasis has been widely recognized as the most lethal threats for cancer patients . Due to their special genetic and environmental context, cancer stem cells (CSCs) which are resistant to most cytotoxic drugs and radiation, are considered as the dominant culprit for metastasis. Thus, the efficient targeting and thorough elimination of CSCs are significantly urgent for the enhancement of therapeutic efficacy. Herein, we developed a facile and smart photothermal-chemo therapeutic nano-assembly system, of which the surface was modified by a sheddable PEG shell and acid-activatable pro-penetration peptide, to surmount the physiological barriers in targeting CSCs. A highly-efficient diradical-featured croconium-based photothermal agent and a natural cytotoxic heat shock protein (HSP) inhibitor were co-loaded in redox-sensitive chitosan matrices to realize the synergistic photothermal-chemo therapy. Within solid tumors, the PEG shell that prevents the nano-assembly from mononuclear phagocytic clearance could rapidly leave to expose the positively charged chitosan, and the detached iRGD could further actuate the tumor penetration of chitosan nanoparticles , and allow the CSCs targeting by selective recognition of CD44 protein. Owing to the HSP inhibition and chemo-sensitization, both the CSCs and non-CSCs could be thoroughly eliminated by the designed nano-assembly, largely inhibiting the tumor growth and metastasis. This work provides a potential strategy for CSCs-targeting drug delivery to solve the CSCs-related metastasis.
研究领域:
肿瘤学
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纳米技术
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药物递送系统
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2020
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IF 8.758
Longfa Kou,Rui Sun,Xinyu Jiang,Xinlu Lin,Huirong Huang,Shihui Bao,Youting Zhang,Chao Li,Ruijie Chen,Qing Yao
Tumor cells usually display metabolic, genetic, and microenvironment-related alterations, which are beneficial to tumor proliferation, tumor development, and resistance occurrence. Many transporters and enzymes, including ATB0,+, xCT, and matrix metalloproteinases (MMPs), are involved in the altered cell metabolism and tumor microenvironment and often abnormally upregulated in malignant tumors. Meanwhile, these dysregulated transporters and enzymes provide targets not only for a pharmacological blockage to suppress tumor progress but also for tumor-specific delivery. Although transporters and MMPs have been widely reported for antitumor drug delivery, the feasibility of utilizing two strategies has never been elucidated yet. Herein, we developed an MMP2-activated and ATB0,+-targeted liposome with doxorubicin and sorafenib (DS@MA-LS) loaded for optimal tumor drug delivery for cancer therapy. DS@MA-LS was designed to prolong blood circulation and deshield the PEG shell from MMP2 cleavage to expose lysine and target overexpressed ATB0,+ for enhanced tumor distribution and cancer cellular uptake. Besides the anticancer effects of loaded drugs, the endocytosed liposomes could further increase ROS production and suppress the antioxidant system to amplify oxidative stress. As expected, DS@MA-LS displayed enhanced targeted drug delivery to tumor sites with the MMP2-controlled ligand exposure and ATB0,+-mediated uptake. More importantly, DS@MA-LS successfully inhibited the tumor growth and cancer cell proliferation both in vitro and in vivo by enhancing apoptosis and ferroptosis, which thanks to the increased ROS generation and impaired GSH synthesis synergistically amplified oxidative stress. Our results suggested that the tumor microenvironment-responsive, multistaged nanoplatform, DS@MA-LS, has excellent potential for optimal drug delivery and enhanced cancer treatment.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2020
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IF 4.902
Yunyan Chen,Mengfei Guo,Ding Qu,Yuping Liu,Jian Guo,Yan Chen
The accumulation and penetration of antitumor drugs in tumor tissues are directly related to their antitumor effects. The particle size of the nanodrug delivery system is one of the most important factors for the accumulation and penetration of antitumor drugs within tumor tissues. Generally, nanodelivery systems of intermediate size (100–120 nm) are capable of efficient accumulation owing to prolonged circulation and enhanced permeability and retention (EPR) effect; however, smaller ones (20–40 nm) are effective for deep penetration within tumor tissue. Currently a conventional drug delivery system cannot possess two types of optimal sizes, simultaneously. To solve this and to enhance cervical cancer treatment, a furin-responsive triterpenine-based liposomal complex (PEGcleavable Tf-CTM/L), with Tf-CTM (transferrin-modified tripterine-loaded coix seed oil microemulsion) in core, coated with a thermo-sensitive lipid and a kind of PEG shell modified with a furin-cleavable peptide was developed to improve tumor-specific accumulation and penetration. Herein, PEGcleavable Tf-CTM/L was capable of efficient accumulation because of EPR effect. The PEG shells could timely detach under stimulation of overexpressed furin protein to solve the problem of the steric hindrance dilemma. The small-sized Tf-CTM released under stimulation of tumor microthermal environment in cervical cancer, which was efficient with regards to deep penetration at tumor sites. Notably, compared to the use of triterpenine alone, PEGcleavable Tf-CTM/L promoted anticervical efficacy and displayed diminished systemic toxicity by efficient accumulation and deep penetration of antitumor drugs within tumor tissues. Our study provides a new strategy, and holds promising potential for anticervical cancer treatment.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Yan Liang,Ping-Yu Wang,You-Jie Li,Ze-Yun Liu,Ran-Ran Wang,Guang-Bin Sun,Hong-Fang Sun,Shu-Yang Xie
Reduced drug uptake and elevated drug efflux are two major mechanisms in cancer multidrug resistance (MDR). In the present study, a new multistage O 2 -producing liposome with NAG/R8-dual-ligand and stimuli-responsive dePEGylation was developed to address the abovementioned issues simultaneously. The designed C-NAG-R8-PTXL/MnO 2 -lip could also achieve magnetic resonance imaging (MRI)-guided synergistic chemodynamic/chemotherapy (CDT/CT). In vitro and in vivo studies showed that C-NAG-R8-PTXL/MnO 2 -lip enhanced circulation time by PEG and targeted the tumor site. After tumor accumulation, endogenous l -cysteine was administered, and the PEG-attached disulfide bond was broken, resulting in the dissociation of PEG shells. The previously hidden positively charged R8 by different lengths of PEG chains was exposed and mediated efficient internalization. In addition, the oxygen (O 2 ) generated by C-NAG-R8-PTXL/MnO 2 -lip relieved the hypoxic environment within the tumor, thus reducing the efflux of chemotherapeutic drug. O 2 was able to burst liposomes and triggered the release of PTXL . The toxic hydroxyl radical (·OH), which was produced by H 2 O 2 and Mn 2+ , strengthened CDT/CT. C-NAG-R8-PTXL/MnO 2 -lip was also used as MRI contrast agent , which blazed the trail to rationally design theranostic agents for tumor imaging.
研究领域:
药学
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生物医学工程
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癌症研究
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纳米技术
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分子生物学
✓ 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）