VETERINARY RESEARCH
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2018
·Vol. 49
·期 1
·1-9
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IF 2.903
Hu Gaowei,Zheng Wenlv,Li Ao,Mu Yaru,Shi Mingyu,Li Tuofan,Zou Haitao,Shao Hongxia,Qin Aijian,Ye Jianqiang
Cell-penetrating peptide (CPP) is a promising cargo for delivering bioactive molecules. In this study, the N terminus of VP1 from chicken anemia virus, designated as CVP1, was found to carry enriched arginine residues with α-helix. By confocal imaging, flow cytometry and MTT assay, we identified CVP1 as a novel, safe and efficient CPP. CVP1-FITC peptide could entry different types of cells tested with dose dependence, but without cytotoxic effects. Compared with TAT-FITC peptide, the CVP1-FITC peptide showed much higher cell-penetrating activity. Moreover, CVP1 could successfully deliver β-glycosidase, poly (I:C) and plasmid into HCT116 cells. Inhibitors and temperature sensitivity analysis further indicated that the cell-penetrating activity of CVP1 was based on ATP-dependent and caveolae-mediated endocytosis. All these data demonstrate that CVP1 has efficient cell-penetrating activity and great potential for developing a novel delivery vector.
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Journal of Materials Chemistry B
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2018
·Vol. 6
·期 5
·797-808
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IF 4.776
Yunti Zhang,Qimin Jiang,Bo Bi,Luming Xu,Jia Liu,Renxi Zhuo,Xulin Jiang
This article describes a novel reduction degradable supramolecular nanoparticle gene delivery system via host–guest interaction based on cyclodextrin-conjugated polyaspartamide with disulfide linkage (Pasp-SS-CD) and adamantyl-terminated polyethylenimine (Ad4-PEI). The reduction responsiveness of Pasp-SS-CD and the Pasp-SS-CD/Ad4-PEI/pDNA supramolecular nanoparticles (SNPs) in the presence of DL-dithiothreitol (DTT) was confirmed by SEC-MALLS and DLS analysis, respectively. Compared with the Ad4-PEI/pDNA polyplexes, the bioreducible supramolecular polycation/pDNA polyplexes exhibited smaller particle size, slightly higher zeta potential, lower cytotoxicity and hemolysis ratio, improved cellular internalization and higher gene transfection efficiency. It was found that introducing Pasp-SS-CD to assemble Ad4-PEI could substantially enhance the tolerance of protein adsorption and maintain the gene transfer capacity of polycationic carriers, which might be beneficial for in vivo use. In addition, the cellular uptake pathway of the supramolecular polycation/pDNA polyplexes was investigated using different uptake inhibitors. The present study demonstrates that the proper assembly of cyclodextrin-conjugated polyaspartamide and adamantyl-terminated polyethylenimine is an effective strategy for the production of a new gene delivery system.
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Advanced Science
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2024
·
IF 14.3
Shuangqian Yan,Panpan Xue,Ying Sun,Tingjie Bai,Sijie Shao,Xuemei Zeng
The dysregulated cholesterol metabolism in breast cancer cells drives malignancy, invasion, and metastasis, emphasizing the significance of reducing abnormal cholesterol accumulation for effective cancer treatment and metastasis inhibition. Despite its promise, cholesterol oxidase (ChOx) encounters challenge due to limited catalytic efficiency and susceptibility to harsh conditions. To overcome these hurdles, biocompatible nanoplatforms (Cu-HPB/C) tailored for efficient cholesterol depletion are introduced. Cu 2+ -doped hollow Prussian blue (Cu-HPB) acts as a carrier, shelter, and enhancer for ChOx, bolstering tumor-targeting ability, stability, and enzymatic activity. Tumor-responsive released Cu 2+ notably augments ChOx activity, facilitating cholesterol depletion and disrupting lipid rafts, thereby impeding cell invasion and migration. Additionally, H 2 O 2 generated from the oxidase reaction enhances Cu-HPB's chemo dynamic therapeutic efficacy. Transcriptomic analysis validates Cu-HPB/C's impact on cholesterol homeostasis and reveals cell death mechanisms including oxidative stress, ferroptosis, cuproptosis, and apoptosis. Demonstrating therapeutic efficacy in both 4T1 tumor subcutaneous and metastasis mouse models, the study presents a direct and effective strategy for tumor therapy and metastasis inhibition through enhanced cholesterol depletion.
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Nano Today
·
2024
·
IF 13.2
Xiuhua Pan,Jie Yang,Ruixin Kang,Jun Zhang,Zongwei Hu,Ning Yang,Zengyi Liu,Zengguang Jia,Xiawei Zhou,Qi Shen
The induction of ferroptosis in cancer cells has emerged as a promising approach to initiate immunogenic cell death (ICD). However, the limited production of lipid peroxidation (LPO) considerably undermines the effectiveness of ferroptosis. In this work, T7 polypeptide engineered bacterial outer membrane vesicles (T7-OMVs) co-delivering plasmids and melanin nanoparticles (MNPs) are fabricated into nanoclusters (TO@Mp) for LPO amplification. The clustered regularly interspaced short palindromic repeats (CRISPR) system as the gene editing tool can knockdown glutathione peroxides 4 ( GPX4 ) to amplify LPO accumulation. Photothermal MNPs exhibit an intrinsic capacity of up-regulating Acyl-CoA synthetase long chain family member 4 (ACSL4) and generating reactive oxygen species (ROS), thereby cooperating with GPX4 gene knockdown to reinforce ferroptosis. While the TO@Mp NPs augment ICD via synergistic lipid peroxidation induced ferroptosis, the mechanism of proinflammatory response acquired by the RNA-seq analysis also indicates that the nanoclusters activate the toll like receptor (TLR) pathways, thereby coordinately potentiating DCs maturation and T cells immunity to restrain tumor growth and metastasis. Conclusively, the biomimetic bacteria-derived platform for synergistic CRISPR-photothermo modulation represents an appealing way for tumor suppression and immunological therapy, which holds great potential in clinical translation for cancer treatment.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
·
IF 4.5
MengYing Lei,Qing Chen,Yang Wang,Gang Wang
Oral absorption of carrier-free self-assembly nanoplatform was limited by mucus barrier, p-gp efflux and liver metabolism. In this study, Pip-Cur-TA nanoparticle were constructed by co-assembly of tannic acid, curcumin and piperine via inter-molecular hydrogen-bonded and π-π interaction to improve the oral chemotherapy. The optimized Pip-Cur-TA nanoparticle showed an average diameter of 60 nm with a drug encapsulation efficiency of 67.02 % and loading capacity of 61.37 %. Pip-Cur-TA nanoparticles showed pH-dependent drug release, mucosal adhesion, inhibition of p-gp and liver metabolism and improved membrane permeability. Oral Pip-Cur-TA nanoparticle produced high oral delivery efficiency and relative oral bioavailability of 12.84 % in rats, and further showed significant tumor inhibition on PC-3 tumor cells. These findings confirmed that Pip-Cur-TA nanoparticle might be a promising oral drug formulation for chemotherapy.
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JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Huang Lanli,Yao Yi,Ruan Zhuren,Zhang Shengqing,Feng Xianjing,Lu Chun,Zhao Jinmin,Yin Feiying,Cao Cunwei,Zheng Li
Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.
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Analytical Methods
·
2025
·
IF 2.6
Xue Kong,Yan Liu,Jinghui Lyu,Zheng-Zhi Yin,Yi Zhang
Osteopontin (OPN) is an important biomarker for reflecting osteoarthritic inflammation and endochondral ossification. In the field of electroanalysis, OPN belongs to non-electroactive protein, which is usually detected by means of an outer probe or biolabel. Here, a novel microsensor can directly electroanalyze OPN, which was constructed by coordinating surface molecularly imprinted polymer (SMIP) with a built-in electroactive probe of poly (methylene blue) (pMB) on an acupuncture needle microelectrode (ANME). The OPN template can be reversibly anchored using 4-mercaptophenylboric acid (4-MBPA) via a borate bond between phenylboronic acid and the external cis-diol of the glycoprotein. Methylene blue (MB) and dopamine (DA) were sequentially electropolymerized and grown around templates, which played pivotal roles in the detection signal from the built-in pMB through the imprinted nanocavities. After the recombination of OPN molecules with imprinted nanocavities, the current strength of built-in pMB could be impeded with a highly sensitive response. This microsensor shows a linear relationship to the concentration of OPN from 0.01 to 1000 ng mL-1 with a detection limit of 3 pg mL-1. The microsensor also exhibits high selectivity and stability, which is attributed to the recognizing ability of the imprinted nanocavities and the hindrance and anti-interference function of coated polydopamine (pDA). This strategy of preparing a sensor shows practical and scientific significance for functionalizing microelectrodes and constructing microsensors for non-electroactive glycoproteins. In the future, it will be fascinating to integrate this microsensor with the acupuncture technique.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2017
·
IF 3.756
Yue Yang,Xiaoyu Lu,Qi Liu,Yu Dai,Xiaojie Zhu,Yanli Wen,Jiaqiu Xu,Yang Lu,Di Zhao,Xijing Chen,Ning Li
Combination therapy with two drugs and nanoparticle-based drug delivery systems are widely applied to reduce the adverse effects of traditional treatment by chemotherapeutic drugs. Palmitoyl ascorbate (PA) as a lipophilic derivative of ascorbic acid shows the advantages in cancer treatment. The aim of the study was to prepare a doxorubicin (DOX) and PA co-loaded liposome to synergistically treat tumor and effectively alleviate the toxicity caused by DOX. The effects were evaluated by in vitro and in vivo studies. The liposomes (weight ratio of DOX to PA = 1:20, DOX 1 /PA 20 -LPs) exhibited the strongest synergistic effects, combination index was 0.38, 0.56, and 0.05 in MCF-7, HepG2, and A549 cells, respectively. In vitro cellular uptake study, the intercellular concentration of DOX in DOX 1 /PA 20 -LPs was 2.5-fold greater than DOX loaded liposome, and DOX 1 /PA 20 -LPs was taken in not only by macropinocytosis, but also by clathrin-mediated endocytosis. Intracellular distribution experiment showed that DOX 1 /PA 20 -LPs efficiently concentrated in the nucleus. In vivo studies indicated that co-encapsulated liposome not only showed the strongest antitumor ability by tumor growth suppression, but also significantly enhanced the safety by the change of body weight and reduced damages to other tissues (evidenced by histopathology study). These results indicated that DOX and PA co-delivery liposome successfully enhanced the anticancer efficacy and mitigated the toxicities of DOX, which displayed potential for clinical application with enhanced safety and efficacy.
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Acta Biomaterialia
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2017
·
IF 6.319
Wenqi Chen,Yong Liu,Xiao Liang,Yu Huang,Quanshun Li
Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient cellular uptake of miR-34a in a CD44-dependent endocytosis way and further facilitate the endosomal escape of miR-34a after 4 h. Through the miR-34a delivery, obvious inhibition of cell proliferation could be detected which was attributed to the enhancement of cell apoptosis and cell cycle arrest , and meanwhile the cell migration and invasion has been observed to be inhibited. Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit the tumor growth and induce the tumor apoptosis owing to the enhanced accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be used as a tumor-targeted oligonucleotide carrier for achieving tumor gene therapy. Statement of Significance The cationic dendrimer PAMAM was modified by chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an efficient cellular uptake and intracellular transfection of miR-34a in a CD44-dependent endocytosis manner. The miR-34a delivery could execute the anti -proliferation activity by simultaneously inducing cell apoptosis and cell cycle arrest, and also the anti -migration activity. The CS-PAMAM-mediated systemic delivery of miR-34a showed significant inhibition of tumor growth and induction of tumor apoptosis using a mice model of subcutaneously implanted tumors.
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ACS Applied Bio Materials
·
2024
·
IF 4.6
Zhaoxin Xia,Yulong Liao,Ge Gao,Shiyong Zhang
The poor accumulation of antibiotics in the cytoplasm leads to the poor eradication of intracellular bacteria. Herein, a polyelectrolyte complex (PECs@Rif) allowing direct cytosolic delivery of rifampicin (Rif) was developed for the treatment of intracellular infections by complexation of poly(α-lipoic acid) (pLA) and oligosaccharide (COS) in water and loading Rif. Due to the thiol-mediated cellular uptake, PECs@Rif delivered 3.9 times higher Rif into the cytoplasm than that of the free Rif during 8 h of incubation. After entering cells, PECs@Rif released Rif by dissociating pLA into dihydrolipoic acid (DHLA) in the presence of intracellular thioredoxin reductase (TrxR). Notably, DHLA could reduce endogenous Fe(III) to Fe(II) and provide a catalyst for the Fenton reaction to produce a large amount of reactive oxygen species (ROS), which would assist Rif in eradicating intracellular bacteria. In vitro assay showed that PECs@Rif reduced almost 2.8 orders of magnitude of intracellular bacteria, much higher than 0.7 orders of magnitude of free Rif. The bacteremia-bearing mouse models showed that PECs@Rif reduced bacterial levels in the liver, spleen, and kidney by 2.2, 3.7, and 2.3 orders of magnitude, respectively, much higher than free Rif in corresponding tissues. The direct cytosolic delivery in a thiol-mediated manner and enhanced oxidative stress proposed a feasible strategy for treating intracellular bacteria infection.
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ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Xiuhua Pan,Feiyang Liu,Ruixin Kang,Zongwei Hu,Yueru Pang,Ziqi Shen,Xiawei Zhou,Jun Zhang,Qi Shen
Despite recent advances in immunotherapy, its efficacy remains constrained by the absence of immune coordination. Especially, the interplay between tumor-draining lymph nodes (TDLNs) and tumors is frequently disregarded. Here, a self-adjuvanting hydrogel capable of eliciting a powerful and sustained immune response is developed. Briefly, the engineered arabinose response bacteria (ARB) expressing IL-15 and mannose-modified hollow mesoporous Prussian blue nanoparticles (NPs) loaded with vitamin E (Man/HMPB(VE), MHV) are mixed with arabinose hydrogel (AraGel), forming the system designated as AraGel@ARB/MHV (AAM). Employing mild photothermal therapy mediated by MHV, immunogenic cell death (ICD) triggers the release of tumor-associated antigens. Subsequently, Man-modified NPs target TDLNs and release VE, which suppresses the checkpoint Src homology region 2 domain-containing phosphatase-1 (SHP1) in dendritic cells, thereby enhancing antigen presentation and T cell activation. Meanwhile, IL-15 expression of ARB(IL-15) induced by AraGel degradation enables ARB to serve as an enhanced adjuvant in a self-adjuvanting manner, working synergistically with ICD and TDLN reprogramming to promote cytotoxic T lymphocytes activation. The hydrogel system efficiently suppresses tumor growth by eliciting prolonged and powerful immunotherapy in an orchestrated manner. Overall, the self-adjuvanting hydrogel holds great potential for cancer immunotherapy.
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ACS Nano
·
2024
·
IF 15.8
Dan Yang,Yuqi Feng,Ying Yuan,Linxuan Zhang,Yao Zhou,Adam C. Midgley,Yanrong Wang,Ning Liu,Guoliang Li,Xiaolin Yao,Dechun Liu
The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an “active PC” to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of “passive PCs” formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.
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