DRUG DELIVERY
·
2019
·
IF 3.829
Lei Fang,Wei Zhang,Zhen Wang,Xinxin Fan,Ziting Cheng,Xiaoya Hou,Daquan Chen
Stability in systemic circulation, effective tumor accumulation, and the subsequent crucial subcellular targeting are significant elements that maximize the therapeutic efficacy of a drug. Accordingly, novel nanoparticles based on polysaccharides that simultaneously presented prolonged systemic circulation and mitochondrial-targeted drug release were synthesized. First, the mitochondrial-targeted polymer, 3,4-dihydroxyphenyl propionic acid-chitosan oligosaccharide-dithiodipropionic acid-berberine (DHPA-CDB), was synthesized, which was used to form self-assembled curcumin (Cur)-encapsulated cationic micelles (DHPA-CDB/Cur). Negatively charged oligomeric hyaluronic acid-3-carboxyphenylboronic acid (oHA-PBA), a ligand to sialic acid and CD44, was further added to the surface of the preformed DHPA-CDB/Cur core to shield the positive charges and to prolong blood persistence. oHA-PBA@DHPA-CDB/Cur formed a covalent polyplex of oHA-PBA and DHPA-CDB/Cur via the pH-responsive borate ester bond between PBA and DHPA. The mildly acidic tumor environment led to the degradation of borate ester bonds, thereby realizing the exposure of the cationic micelles and causing a charge reversal from −19.47 to +12.01 mV, to promote cell internalization and mitochondrial localization. Compared with micelles without the oHA-PBA modification, the prepared oHA-PBA@DHPA-CDB/Cur showed enhanced cytotoxicity to PANC-1 cells and greater cellular uptake via receptor-mediated endocytosis. oHA-PBA@DHPA-CDB/Cur was effectively targeted to the mitochondria, which triggered mitochondrial membrane depolarization. In mice xenografted with PANC-1 cells, compared with control mice, oHA-PBA@DHPA-CDB/Cur resulted in more effective tumor suppression and greater biosafety with preferential accumulation in the tumor tissue. Thus, the long-circulating oHA-PBA@DHPA-CDB/Cur, with mitochondrial targeting and tumor environment charge-reversal capabilities, was shown to be an excellent candidate for subcellular-specific drug delivery.
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ANALYTICA CHIMICA ACTA
·
2019
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IF 5.256
Zhihao Wu,Danyang Nan,Huan Yang,Shuang Pan,Hui Liu,Xiaoli Hu
A facile ratiometric fluorescence method for ascorbic acid (AA) detection was established by combining the fluorescence of MoS 2 quantum dots (QDs) with second-order scattering (SOS) of CoOOH. In MoS 2 QDs/CoOOH nanohybrid system, the fluorescence of MoS 2 QDs was quenched by CoOOH whereas the intensity of SOS was relatively close to the fluorescence due to the intrinsic high scattering ability of large size CoOOH nanoflakes . With the addition of AA, CoOOH nanoflakes were reduced to Co 2+ accompanied the size decline and the disappearance of characteristic absorption in UV–vis spectrum, resulting in the fluorescence recovery and SOS fading. Thus, the ratiometric detection of AA was obtained through the opposite changes of fluorescence and SOS. Under optimized conditions, the detection limit of AA was 0.21 μmol L −1 with a linear range from 0.80 to 32.0 μmol L −1 . Furthermore, the MoS 2 QDs/CoOOH nanohybrid system was applied to the detection of AA in human serum samples and vitamin C tablets with satisfactory results.
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DRUG DELIVERY
·
2022
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IF 6.819
Wan Liu,Meng Cheng,Zhiyang Lu,Haocheng Li,Yulin Feng,Yi Jin,Shilin Yang,Jianfang Feng,Liangxing Tu
Modifying nanocrystals with functional materials have been common strategy to enlarge the enhancing ability on oral absorption via nanocrystals; however, whether the functional materials have played their full enhancing ability in oral absorption is still unknown. In this study, we synthetized a novel chitosan-based copolymer (the copolymer of sodium dodecyl sulfate (SDS), chitosan (CS) and D-α-Tocopherol polyethylene glycol 1000 succinate, SDS-CS-TPGS), and modified nanocrystals with this copolymer, aiming to enhance the oral absorption of polymer andrographolide (ADR). In real-time distribution study, we found the distribution of ADR, SDS, CS and TPGS varies in gastrointestinal tract, while the distribution of ADR and SDS-CS-TPGS was similar, revealing the SDS-CS-TPGS could able to participate in the absorption process of andrographolide timely. To explore the oral absorption enhancing ability of SDS-CS-TPGS, we prepared a series of nanocrystals modified with different materials and explored their pharmacokinetic performances on SD rats. The results showed the nanocrystals modified with SDS-CS-TPGS (S-C-TANs) exhibited the highest bioavailability, which could enhance the AUC0-∞ of ADR from 1.291 mg/L*h to 5.275 mg/L*h (enhanced for about 4.09-folds). The enhanced anti- inflammatory efficacy was also found on ICR mice by employing ear swelling rate, TNF-α, IL-1β and IL-6 and pharmacodynamic index. These results indicated that modified with synthesized copolymer containing different functional stabilizers is an efficient strategy to enlarge the enhancing ability on oral absorption of nanocrystals.
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DALTON TRANSACTIONS
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2022
·Vol. 51
·期 42
·16119-16125
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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.
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CHEMICAL ENGINEERING JOURNAL
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2022
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IF 16.744
Sa Wang,Shuqing Yang,Zhuolin Cui,Xueyan Liu,Yu Yang,Tao Wang,Wenjuan Ma,Yubin Zhou,Ruizheng Liang,Dan Yan,Huizhi Chen
Precise activation of therapeutic molecules in tumor tissues is the key step to ensure targeted antitumor performance and reduce adverse effects towards normal tissues and organs. Although the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), i.e., bioorthogonal chemistry, has been used for the rapid synthesis of anticancer drugs in cells, it remains a great challenge to realize precise in vivo drug synthesis in tumor sites for precise cancer treatment. In this work, we first report the in-situ activation of CuAl-layered double hydroxide (CuAl-LDH) nanosheets to realize Cu(I)-catalyzed bioorthogonal chemistry in vivo in tumor microenvironment (TME) for precise chemotherapy and chemodynamic therapy (CDT). The Cu(II) ions in the biocompatible CuAl-LDH nanosheets can be in-situ reduced to Cu(I) ions partially by the overexpressed glutathione in TME. The generated Cu(I) can serve as a catalyst to catalyze the CuAAC reaction between alkyne and azide in TME, thus realizing in vivo drug synthesis for precise chemotherapy. Meanwhile, the generated Cu(I) can catalyze the Fenton-like reaction to generate toxic hydroxyl radicals (⋅OH) from H 2 O 2 in TME for CDT. Therefore, CuAl-LDHs can be used for the targeted synergistic chemotherapy and CDT to achieve highly precise and efficient elimination of cancer cells in vitro and inhibition of tumors in vivo .
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2022
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IF 9.965
Mengmeng Xu,Yuan Liu,Wanru Luo,Fangrong Tan,Donghua Dong,Weichang Li,LinGe Wang,Qianqian Yu
A multi-functional nanocatalytic system based on combined therapies has attracted considerable research attention in recent years due to its potential in the treatment of cancer. Herein, ZnO 2 @ [email protected] nanoparticles (NPs) based on hydroxyl radical (•OH) mediated chemodynamic therapy (CDT) and glucose-exhausting starvation therapy (ST) were constructed. Specifically, in the acidic tumor microenvironment (TME), the pH responsive decomposition of the shell ZIF-67 triggered the release of the Fenton-like catalyst Co 2+ , after which the exposed zinc peroxide (ZnO 2 ) reacted with H 2 O (H + ) to generate O 2 and hydrogen peroxide (H 2 O 2 ). The generated O 2 could alleviate hypoxia in the TEM and interact with ultra-small Au NPs originally coated on ZnO 2 to catalyze intracellular glucose and to produce another source of H 2 O 2 . While the glucose consumption caused the starvation of tumor cells, the generated H 2 O 2 from dual sources reacted with the catalyst Co 2+ to generate highly toxic •OH for CDT. Systematic in vitro and in vivo experiments were carried out to evaluate this nanocatalytic system, and the results showed an enhanced efficacy of this cancer therapy.
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ACS Applied Materials & Interfaces
·
2022
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IF 10.383
Chunyan Liao,Xiang Wang,Xueying Zhou,Dequan Wang,Ziyin Zhang,Yan Liu,Xiao Wu,Ying Chen,Yifeng Tan,Xin Dai,Pei Jing,Jie Pang,Xiao Xiao,Jie Liu,Xiaoming Liao,Shiyong Zhang
Despite great advances, the development of cancer drugs that can efficiently kill cancer cells while protecting noncancer cells has not been achieved. By using only dietary antioxidants vitamin C (VC) and (R)-(+)-lipoic acid (LA), we herein develop a nanodrug VC@cLAV featuring the above function. After entering cells, cLAV dissociates into LA and DHLA (dihydrolipoic acid, reduced form of LA) and releases VC and DHA (dehydroascorbate, oxidized form of VC). In cancer cells, the two redox pairs recycle each other and dramatically promote the intracellular reactive oxygen species production to kill cancer cells at low doses comparable to cytotoxic drugs. Oppositely in noncancer cells, the LA/DHLA and VC/DHA pairs exert anti-oxidant action to actively protect the organism by preventing the normal cells from oxidative stress and repairing cells suffering from oxidative stress. When compared with the first-line cytotoxic drug, VC@cLAV displayed superior therapeutic outcomes yet without side effects in diverse tumor models including patient-derived xenograft (PDX). This drug with efficient cancer cell killing and noncancer cell protection represents a new cancer therapy.
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Journal of Pharmaceutical Analysis
·
2022
·
IF 14.026
Min Mu,Xiaoyan Liang,Na Zhao,Di Chuan,Bo Chen,Shasha Zhao,Guoqing Wang,Rangrang Fan,Bingwen Zou,Bo Han,Gang Guo
Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer; hence, new and efficient strategies are necessary. In this study, a supramolecular nanoreactor ( [email protected] 3+ ) based on tannic acid (TA), iron ion (Fe 3+ ), and docetaxel (DOC) with microtubule inhibition, reactive oxygen species (ROS) generation, and glutathione peroxidase 4 (GPX4) inhibition, is prepared for ferroptosis/apoptosis treatment. After internalization by CT26 cells, the [email protected] 3+ nanoreactor escapes from the lysosomes to release payloads. The subsequent Fe 3+ /Fe 2+ conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration. Additionally, Fe 3+ can consume glutathione to repress the activity of GPX4 to induce ferroptosis. Meanwhile, the released DOC controls microtubule dynamics to activate the apoptosis pathway. The superior in vivo antitumor efficacy of [email protected] 3+ nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model. Therefore, the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.
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Frontiers in Oncology
·
2020
·
IF 4.848
Zhan Wenhua,Li Hanrui,Guo Yingying,Du Getao,Wu Yayan,Zhang Dexin
Combination chemotherapy is a routine treatment for esophageal cancer, but some shortcomings, such as drug toxicity and side effects, greatly limit the clinical application of combination therapy. To overcome these shortcomings, we have developed a mesoporous silica nanoparticle system that was used to load doxorubicin and β-elemene. β-elemene was encapsulated in the pore of mesoporous silica nanoparticle and doxorubicin was electrostatically adsorbed on the surface of mesoporous silica nanoparticle by hyaluronic acid to construct dual drugs synergistic nanoparticles (bMED NPs, ~77.15 nm). In vitro studies demonstrated that bMED NPs had a good treatment effect in esophageal cancer cell lines. In vivo fluorescence imaging results demonstrated that bMED NPs could accumulate in tumor sites and achieve in vivo long-term circulation and continuous drug release. In addition, bMED NPs exhibited significant antitumor effects in the esophageal cancer mouse model, which may provide a great platform for esophageal cancer chemotherapy.
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DRUG DELIVERY
·
2019
·
IF 3.829
Mengna Liu,Bingjie Wang,Chunjing Guo,Xiaoya Hou,Ziting Cheng,Daquan Chen
In this study, novel multifunctional folic acid, biotin, and CD44 receptors targeted and pH-sensitive “nano-actiniaes” were fabricated with icariin (ICA) and curcumin (Cur) as loaded model drugs for breast cancer therapy. The newly synthesized polymer oligomeric hyaluronic acid-hydrazone bond-folic acid-biotin (Bio-oHA-Hyd-FA) was characterized by 1H NMR spectrogram (proton nuclear magnetic resonance). The obtained drug carrier Bio-oHA-Hyd-FA self-assembled into nanomicelles, named as “nano-actiniaes”, in aqueous media with hydrodynamic diameter of 162.7 ± 5 nm. The size, surface zeta potential, and morphology of the “nano-actiniaes” were observed via TEM. The in vitro release experiment indicated that much more encapsulated icariin (ICA) and curcumin (Cur) were released from the Bio-oHA-Hyd-FA micelles (nano-actiniaes) in the acidic environment. Additionally, the cytotoxicity research demonstrated that the Bio-oHA-Hyd-FA carrier material was completely nontoxic, and the ICA&Cur “nano-actiniaes” had greater cytotoxicity compared with other control groups. In addition, the “nano-actiniaes” were found to significantly inhibit cancer cell invasion by Transwell assay. Moreover, in vivo evaluation of anti-tumor effect illustrated that the ICA and Cur “nano-actiniaes” possessed inhibitory effect on tumors. Consequently, the multi-targeted pH-sensitive “nano-actiniaes” can realize significant tumor targeting and effectively inhibit tumor growth.
研究领域:
药剂学
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肿瘤学
·
生物材料科学
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IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2022
·
IF 3.712
Yunting Zhang,Yuxi Liu,Jianguang Wang,Zongying Jiang,Lin Zhang,Yong Cui,Danyu Zhao,Yanjie Wang
Objective M2-like tumor-associated macrophages (TAMs) play a crucial role in promoting tumor proliferation, angiogenesis, and metastasis. In the current study, we investigated the relationship between macrophage polarization and the antitumor effect of Atractylenolide II (AT-II) in lung cancer cells.Materials and methods Cell viability, migration, and invasion were determined by MTT assay, wound healing assay, and transwell assay, respectively. Flow cytometry analysis showed the percentage of CD206+ cells. Gene expression was determined by real-time PCR, western blotting, and immunofluorescence staining. Lewis lung carcinoma mouse xenograft and metastasis models were used to examine the effects of AT-II on lung cancer in vivo.Results AT-II (2.5 and 5 µM) did not cause significant inhibition of A549 cell viability but markedly inhibited IL-4/IL-13-induced M2-like polarization, evidenced by the decreased expression of the M2 surface marker CD206, down-regulation of specific M2-marker genes (Arg-1, IL-10 and TGF-β) as well as inhibition of M2 macrophages-mediated invasion and migration of A549 cells. In addition, AT-II inhibited IL-4/IL-13-induced activation of the STAT6 signaling pathway that is vital in the M2-like polarization of macrophages. In animal models, administration of AT-II (50 mg kg−1, i.g., QD for 21 days) significantly inhibited tumor growth, reduced pulmonary metastatic nodules, and down-regulated the percentages of M2 macrophages (F4/80+ and CD206+) in total macrophages (F4/80+) in tumor tissues and pulmonary metastatic nodules.Conclusions AT-II effectively inhibits M2-like polarization, thereby inhibiting lung cancer cell metastasis both in vivo and in vitro, revealing a novel potential strategy for the antitumor effect of AT-II.
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BIOORGANIC & MEDICINAL CHEMISTRY
·
2015
·
IF 2.793
Cheng-Ting Zi,Dan Yang,Fa-Wu Dong,Gen-Tao Li,Yan Li,Zhong-Tao Ding,Jun Zhou,Zi-Hua Jiang,Jiang-Miao Hu
A series of perbutyrylated glycosides of podophyllotoxin and its derivatives were synthesized and evaluated for their antitumor activity in vitro. Most of them exhibit cytotoxic activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays . Among the synthesized compounds, epipodophyllotoxin α- d -galactopyranoside 8b , epipodophyllotoxin α- d -arabinopyranoside 8e , and podophyllotoxin β- d -glucopyranoside 11a show the highest potency of anticancer activity with their IC 50 values ranging from 0.14 to 1.69 μM. Structure activity relationship analysis indicates that the type of glycosidic linkage , the configuration at C-4 of the podophyllotoxin scaffold, and the substitution at 4′-position (OH vs OCH 3 ) can all have significant effect on the potency of their anticancer activity. Several compounds are more active than the control drugs Etoposide and Cisplatin , suggesting their potential as anticancer agents for further development.
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