LANGMUIR
·
2023
·
IF 3.9
Shui Ling Yi,Zi Ling Li,Yan Chun Gong,Xiang Yuan Xiong
Transferrin-conjugated polymersomes, transferrin–biotin/avidin/biotin–Pluronic F127–poly(lactic acid) (Tf-F127-PLA), were successfully prepared through a biotin–avidin bridging technique to study their ability to inhibit multidrug resistance of cancer cells. Hydrophilic doxorubicin (DOX) was selected as the model drug to be loaded into Tf-F127-PLA polymersomes. DOX loaded in Tf-F127-PLA polymersomes was released fast initially, followed by a slow release. The effect of the transferrin ligand density of Tf-F127-PLA/DOX polymersomes on their targeting properties was studied by both cytotoxicity and cellular uptake assays against A549 lung cancer cells. It was shown that Tf-F127-PLA/DOX polymersomes had better targeting ability than nontargeted drug-loaded polymersomes. Furthermore, Tf-F127-PLA/DOX polymersomes with 2% Tf molar content have more effective antitumor activity and a higher cellular uptake than those with 4 and 5% Tf molar content. 2% Tf-F127-PLA/DOX polymersomes also exhibited better anticancer ability in multidrug resistant cancer cells A549/ADR than nontargeted PLA-F127-PLA/DOX polymersomes. It was further proved that the endocytosis of polymersomes by A549/ADR cells was an energy-dependent endocytosis process, which was related to clathrin, macrocytosis, and caveolin. Also, the endocytosis of Tf-F127-PLA/DOX polymersomes was proven to be mediated by the transferrin receptor.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Xin Wang,Jinshuang Hu,Hua Wei,Zihan Li,Jian Liu,Jie Zhang,Shenghong Yang
Carbon dots (CDs) provides unprecedented opportunities for optical applications due its unique properties, but the energy-extensive consumption, high-risk factor and time-consuming synthesis procedure greatly hinders its industrialization process. Herein, we proposed an ultra-low energy consumption solvent-free synthetic strategy for fast preparing green/red fluorescence carbon dots (G-/R-CDs) using m-/o-phenylenediamine and primary amine hydrochloride. The involvement of primary amine hydrochloride can improve the formation rate of G-CDs/R-CDs through effectively absorbing microwave energy and providing acid react environment. The developed CDs exhibit good fluorescence efficiency, optical stability and membrane permeability for dexterous bioimaging in vivo. Based on inherently high nitrogen content, the G-CDs/R-CDs possess excellent nuclear/nucleolus targeting ability, and were successfully applied for screening cancer and normal cells. Furthermore, the G-CDs/R-CDs were further applied for fabricating high-safety and high-color rendering index white light-emitting diodes, providing a perfect candidate for indoor lighting. This study opens up new horizons for advancing practical applications of CDs in related fields of biology and optics .
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Small Methods
·
2023
·Vol. 7
·期 6
·2201548
·
IF 12.4
Pengfei Yuan,Xinjie Chen,Xiaodi Li,Xiaoqing Zong,Caiqi Yang,Yuchao Li,Wei Xue,Jian Dai
Cell membrane-cloaked nanoparticles are exploited as a promising drug carrier to enhance circulation, accumulation, penetration into tumor sites and cellular internalization. However, the effect of physicochemical properties (e.g., size, surface charge, shape, and elasticity) of cell membrane-cloaked nanoparticles on nano-bio interaction is rarely studied. In the present study, keeping the other parameters constant, erythrocyte membrane (EM)-cloaked nanoparticles (nanoEMs) with different Young's moduli are fabricated by altering different kinds of nano-core (i.e., aqueous phase core, gelatin nanoparticles, and platinum nanoparticles). The designed nanoEMs are used to investigate the effect of nanoparticle elasticity on nano-bio interaction including cellular internalization, tumor penetration, biodistribution, blood circulation, and so on. The results demonstrate that the nanoEMs with intermediate elasticity (≈95 MPa) have a relatively higher increase in cellular internalization and inhibition of tumor cells migration than the soft (≈11 MPa) and stiff (≈173 MPa) ones. Furthermore, in vivo studies show that nanoEMs with intermediate elasticity preferentially accumulate and penetrate into tumor sites than the soft and stiff ones, while in circulation, softer nanoEMs show a longer blood circulation time. This work provides an insight for optimizing the design of biomimetic carriers and may further contribute to the selection of nanomaterials on biomedical application.
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CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Gongxi Qiao,Xuming Pan,Mengyun He,Ruixi Peng,Xiangrong Huang,Cunpeng Nie,Jianhui Jiang,Xia Chu
Tumor protein 53 (Tp53), a key regulator of suppressor genes, is commonly mutated in numerous malignant diseases. Consequently, elimination mutant protein 53 (mutp53) represents an appealing strategy for treating mutp53-related tumors. However, the treatment of these mutations remained challenging due to its formidable limitations. In this study, by loading glucose oxidase (GOX) into Zn-based layered double hydroxides (Zn-LDH) interlayer, a pH-responsive ultrathin nanotherapeutic platform (Zn-LDH@GOX) was created to suppress tumors growth by degrading mutp53. Upon exposure to the acidic environment of lysosomes, the lattice structure of Zn-LDH@GOX was partially disrupted, leading to the release of Zn 2+ ions and GOX into the cytoplasm. The increased intracellular concentration of Zn 2+ facilitated the restoration of wild-type protein 53 (wtp53) conformation, which in turn degraded mutp53 through activated autophagic pathways. Meanwhile, GOX-induced Heat Shock Protein 90 (HSP90) disruption resulted in the liberation of mutp53 from the HSP90/mutp53 complex and reactivated its degradation via the ubiquitination-mediated proteasomal pathway. In vitro and in vivo experiments confirmed the significant suppression of mutp53 expression and inhibition of tumor growth by Zn-LDH@GOX. Our work offers a novel pH-responsive nanotherapeutic platform with immense potential for mutp53 tumor-specific therapy.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Xucan Yang,Lulu Cheng,Yile Zhao,Haoran Ma,Haitao Song,Xuanmin Yang,Kang-Nan Wang,Yanrong Zhang
The efficacy of imaging-guided photodynamic therapy (PDT) is compromised by the attenuation of fluorescence and decline in reactive oxygen species (ROS) generation efficiency in the physiological environment of conventional photosensitizers , limited near-infrared (NIR) absorption, and high systemic cytotoxicity. This paper presents the synthesis of two cyclometalated Ir (III) complexes (Ir-thpy and Ir-ppy) by using a triphenylamine derivative (DPTPA) as the primary ligand and their encapsulation into an amphiphilic phospholipid to form nanoparticles (NPs). These complexes exhibit aggregation-induced emission features and remarkably enhanced ROS generation compared to Chlorin e6 (Ce6). Moreover, Ir-thpy NPs possess the unique ability to selectively target mitochondria , leading to depolarization of the mitochondrial membrane potential and ultimately triggering apoptosis. Notably, Ir-thpy NPs exhibit exceptional photocytotoxicity even towards cisplatin-resistant A549/DDP tumor cells. In vivo two-photon imaging verified the robust tumor-targeting efficacy of Ir-thpy NPs. The in vivo results unequivocally demonstrate that Ir-thpy NPs exhibit excellent tumor ablation along with remarkable biocompatibility. This study presents a promising approach for the development of multifunctional Ir-NPs for two-photon imaging-guided PDT and provides novel insights for potential clinical applications in oncology.
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Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Qiu-Ping Feng,Yu-Ting Zhu,Yi-Zhen Yuan,Wen-Jie Li,Hao-Han Yu,Meng-Yuan Hu,Su-Yun Xiang,Shu-Qin Yu
In this study, to improve the intestinal absorption of small molecule chemotherapeutic drug docetaxel (DTX) and macromolecular monoclonal antibody drug bevacizumab (BVZ), we designed and prepared a type of co-delivery nanoparticles for the oral administration of DTX and BVZ. Carboxymethyl chitosan (CMC) and poly(lactic- co -glycolic acid) (PLGA) were used as the carrier of DTX nanoparticles (CPNP DTX ), and methoxy polyethylene glycol-poly (β-amino ester) (mPEG-PAE) was used as the carrier of BVZ nanoparticles (PPNP BVZ ). Then, the two nanoparticles were physically mixed in mass ratios to form mixed co-delivery nanoparticles, which was named as CPNP DTX &PPNP BVZ . The nanoparticles were characterized with pH-sensitive drug release property. CPNP DTX &PPNP BVZ could significantly increase the bioavailability of DTX and BVZ according to the more cellular uptake in Caco-2 cells and the higher absorption in the intestinal tissue. Compared with free DTX and BVZ, CPNP DTX &PPNP BVZ showed excellent cytotoxic effects on A549 cells. Our study revealed the potential of co-delivery nanoparticles of binary mixture of chemotherapeutic small molecule and macromolecular antibody drug as an oral administration therapeutic system.
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ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Meng-Xian Liu,Na Ding,Shuai Chen,Yong-Liang Yu,Jian-Hua Wang
Lipid droplets (LDs) are intracellular lipid-rich organelles, which not only serve as neutral lipid reservoirs but also involve in many physiological processes and are associated with a variety of metabolic diseases and cancers. Long-term tracking of the state and behavior of LDs is of great significance but challenging. The difficulty is largely due to the lack of low cytotoxicity, high photobleaching resistance, and long intracellular retention probes that are capable of long-term tracking LDs. Herein, we report the discovery of two amphiphilic LD-targeting carbon nanoparticles (CNPs, i.e., CPDs and CDs) prepared by one-step room-temperature and hydrothermal methods. Their high lipid–water partition coefficient (log P > 2.13) and strong positive solvatochromism property ensure the quality of LD imaging. Especially, CDs exhibit favorable biocompatibility (2 mg mL–1, cell viability >90%), excellent photostability (after continuous laser irradiation on a confocal microscope for 2 h, relative FL intensity >85%), and superior intracellular retention ability, thereby enabling long-term tracking of LDs in hepatocytes for up to six passages. Based on the excellent long-term tracking ability, CDs are successfully applied to observe autophagy in a typical catabolic process and to evaluate the effect of a commonly used lipid-lowering drug atorvastatin on hepatocyte lipid uptake.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Yuping Wei,Caiying Zhang,Man Zhang,Qionghong Niu,Fengli Hui,Zi Liu,Xia Xu
In our previous study, a novel cell penetrating peptide (CPP) R7 (Arg-Arg-Arg-Arg-Arg-Trp-Trp, RRRRRWW) has been developed to help cellular internalization of paclitaxel (PTX) through the non-covalent interaction with CPP. However, the facilitation mechanism of R7 mediated PTX translocation is not clear. Here the uptake pathways of R7 and R7-PTX were investigated by in vitro test and molecular simulations. In vitro experiments reveal that both R7 and R7-PTX complex translocate through the direct translocation and clathrin mediated endocytosis and associate with the macropinocytosis pathway at high CPP concentration. The translocation of R7(0.1 mM)-PTX complex further involves the lipid raft/caveolae mediated endocytosis. The simulation results show that the synergistic effect between R7 and PTX not only changes the penetration energy barrier but also activates the macropinocytosis and lipid raft/caveolae mediated pathway, resulting in the improvement in the translocation. The presence of heparin also improves the R7 and R7-PTX translocation. These studies provide a theoretical basis for understanding PTX delivery facilitated by the synergistic effect between CPP and cargo and paves a way for CPP design.
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Nature Communications
·
2021
·Vol. 12
·期 1
·1-14
·
IF 14.919
Weng Qinjie,Sun Heng,Fang Chunyan,Xia Fan,Liao Hongwei,Lee Jiyoung,Wang Jincheng,Xie An,Ren Jiafeng,Guo Xia,Li Fangyuan,Yang Bo,Ling Daishun
Acute kidney injury (AKI) is a prevalent and lethal adverse event that severely affects cancer patients receiving chemotherapy. It is correlated with the collateral damage to renal cells caused by reactive oxygen species (ROS). Currently, ROS management is a practical strategy that can reduce the risk of chemotherapy-related AKI, but at the cost of chemotherapeutic efficacy. Herein, we report catalytic activity tunable ceria nanoparticles (CNPs) that can prevent chemotherapy-induced AKI without interference with chemotherapeutic agents. Specifically, in the renal cortex, CNPs exhibit catalytic activity that decomposes hydrogen peroxide, and subsequently regulate the ROS-involved genes by activating the Nrf2/Keap1 signaling pathway. These restore the redox homeostasis for the protection of kidney tubules. Under an acidic tumor microenvironment, CNPs become inert due to the excessive H + that disrupts the re-exposure of active catalytic sites, allowing a buildup of chemotherapy-mediated ROS generation to kill cancer cells. As ROS-modulating agents, CNPs incorporated with context-dependent catalytic activity, hold a great potential for clinical prevention and treatment of AKI in cancer patients.
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ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Lei Luo,Min Wang,Yuan Zhou,Dongliu Xiang,Qing Wang,Jin Huang,Jianbo Liu,Xiaohai Yang,Kemin Wang
For intracellular molecular detection, the appropriate probes should include the abilities to enter target cells noninvasively, target specific sites, and then respond to the analytes reliably. Herein, a ratiometric fluorescent DNA nanostructure (RFDN) was designed for mitochondrial adenosine triphosphate (ATP) imaging in living cells. The DNA nanostructure was constructed by continuous hybridization of two hairpin DNA strands (HS1-Cy3 and HS2-Cy5) under the initiation of the trigger. HS1-Cy3 and HS2-Cy5 contained split aptamer fragments of ATP and are labeled with a fluorescent donor (Cy3) and acceptor (Cy5), respectively. The RFDN integrated multiple split aptamer fragments and increased the local concentration of sensing probes. The binding of ATP to aptamer fragments on the RFDN shortened the distance between Cy3 and Cy5, resulting in obvious ratiometric signals (fluorescence resonance energy transfer). The RFDN showed good biocompatibility and can be internalized into cells in a caveolin-dependent endocytosis pathway. The co-localization imaging results indicated that the DNA nanostructure could target the mitochondria via Cy3 and Cy5. Moreover, the confocal imaging results showed that the intracellular ATP changes stimulated by drugs in living cells could be indicated by the RFDN. In this way, the RFDN is expected to be a simple, flexible, and general platform for chemo/biosensing in living cells.
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CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Zhanlin Zhang,Hui Yan,Shang Li,Yuan Liu,Pan Ran,Weijia Chen,Xiaohong Li
The navigation of drug-loaded nanocarriers is confronted with series of physiological and pathological barriers in blood circulation, tissue penetration and cell internalization. In the current study, self-propelled micromotors of fiber rods are proposed to address the transportation barriers of chemotherapeutic drugs. Fiber rods with distinct Janus structure are prepared by side-by-side electrospinning, and urease and folate are conjugated on the respective sides of Janus rods (JRs) as power source and targeting ligands of Janus micromotors (JMs). The grafting density of urease determines the motion velocity and trajectory of JMs, and the high motion velocity and large mean-square displacement are detected in both phosphate-buffered saline and simulated extracellular matrices of tumor tissues. Despite no interference with the uptake pathway, the self-propelled motion promotes the folate-mediated cell internalization of JMs and maximizes the toxicities and apoptosis rate of tumor cells. The self-propulsion force from one side of JMs enhances the lateral drift and extravasation across blood vessel walls, increasing their accumulation in tumor tissues by around 2 folds and, doxorubicin accumulation, by around 2.6 folds. The treatment with JMs remarkably inhibits the tumor growth, prolongs the animal survival rate and induces strong tumor necrosis without obvious histopathological and hematological abnormalities to normal tissues. Thus, this study demonstrates a feasible strategy in combating the navigation barriers of blood vessel extravasation, tumor tissue diffusion and cell capture, effectively promoting the treatment efficacy and alleviating side effects of chemotherapeutic agents.
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ACS Nano
·
2020
·
IF 14.588
Dengshuai Wei,Yingjie Yu,Xingcai Zhang,Yongheng Wang,Hao Chen,Yao Zhao,Fuyi Wang,Guanghua Rong,Wenwen Wang,Xiang Kang,Jing Cai,Zehua Wang,Ji-Ye Yin,Muhammad Hanif,Yongbing Sun,Gaofeng Zha,Linxian Li,Guohui Nie,Haihua Xiao
Excessive oxidative stress in cancer cells can induce cancer cell death. Anticancer activity and drug resistance of chemotherapy are closely related to the redox state of tumor cells. Herein, five lipophilic Pt(IV) prodrugs were synthesized on the basis of the most widely used anticancer drug cisplatin, whose anticancer efficacy and drug resistance are closely related to the intracellular redox state. Subsequently, a series of cisplatin-sensitive and drug-resistant cell lines as well as three patient-derived primary ovarian cancer cells have been selected to screen those prodrugs. To verify if the disruption of redox balance can be combined with these Pt(IV) prodrugs, we then synthesized a polymer with a diselenium bond in the main chain for encapsulating the most effective prodrug to form nanoparticles (NP(Se)s). NP(Se)s can efficiently break the redox balance via simultaneously depleting GSH and augmenting ROS, thereby achieving a synergistic effect with cisplatin. In addition, genome-wide analysis via RNA-seq was employed to provide a comprehensive understanding of the changes in transcriptome and the alterations in redox-related pathways in cells treated with NP(Se)s and cisplatin. Thereafter, patient-derived xenograft models of hepatic carcinoma (PDXHCC) and multidrug-resistant lung cancer (PDXMDR) were established to evaluate the therapeutic effect of NP(Se)s, and a significant antitumor effect was achieved on both models with NP(Se)s. Overall, this study provides a promising strategy to break the redox balance for maximizing the efficacy of platinum-based cancer therapy.
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