查找使用阿拉丁产品的科研文献

Acid and reduction stimulated logic “and”-type combinational release mode achieved in DOX-loaded superparamagnetic nanogel

Meifang Song,Yanan Xue,Lidi Chen,Xiaoyang Xia,Yang Zhou,Lei Liu,Bo Yu,Sihui Long,Shiwen Huang,Faquan Yu

A superparamagnetic nanogel featured with a logic “and”-type pH/reduction combinational stimulated release mode was fabricated as a drug delivery system by virtue of parallel crosslinking. The disulfide bond and electrostatic interaction between thiolated alginate (SA–SH) and thiolated/aminated iron oxide nanoparticles (SH–MION–NH 2 ) were employed to achieve the mechanism. The obtained DOX-loaded magnetic nanogel is 122.7   ±   20.3   nm in size with superparamagnetism. The combinational conditions of pH   5.0/10   mM glutathione (GSH) stimulated a significantly high accumulative release. However, either pH   7.4/10   mM (GSH) or pH   5.0 alone induced much low release. This verified the typical logic “and”-type combinationally stimulated release mode. In vitro cytotoxicity tests clearly illustrated the effective selectivity of killing the human cervical cancer cells (HeLa) with IC 50 of 1.01   μg/mL and the human hepatoma cells (HepG2) with IC 50 of 1.57   μg/mL but significantly low cytotoxicity to the cercopithecus aethiops kidney cells (Vero). CLSM presented the internationalization of the nanogel into cytoplasm and nuclei with time. In vivo investigation revealed that the selective intratumoral accumulation and antitumor efficacy were considerably advantageous over free DOX whereas low systemic toxicity exhibited up-regulated security as compared to free DOX. Overall, the DOX-loaded magnetic nanogel with enhanced antitumor efficacy and down-regulated adverse effect was a promising nanoplatform for the clinical chemotherapy of malignancy.

PEGylated Oxidized Alginate-DOX Prodrug Conjugate Nanoparticles Cross-Linked with Fluorescent Carbon Dots for Tumor Theranostics

Xu Jia,Mingliang Pei,Xubo Zhao,Kun Tian,Tingting Zhou,Peng Liu

Theranostic nanomedicine has recently emerged as an appealing approach for tumor chemotherapy. Here, for the first time, fluorescent carbon dots (Cdots) were used as cross-linker for tumor theranostic nanoparticles. Novel theranostic nanoparticles of approximately 27 nm with a doxorubicin (DOX) content of 0.2532 mg/mg (mPEG-OAL-DOX/Cdots) were designed by conjugating DOX onto mPEG-OAL/Cdots nanoparticles that were prepared by cross-linking the PEGylated oxidized alginate (mPEG-OAL) with Cdots. Due to the acid-labile Schiff base conjugating linkage, the theranostic prodrug nanoparticles showed low levels of DOX release in the simulated physiological media, which indicated premature drug leakage could be reduced during body circulation. Interestingly, the in vitro DOX release was triggered in the simulated tumor microenvironment without burst release. MTT assay and CLSM analysis showed that the mPEG-OAL/Cdots nanoparticles were noncytotoxic, but that the mPEG-OAL-DOX/Cdots theranostic nanoparticles exhibited high degrees of inhibition of cancer cells due to their nucleus-targeting DOX delivery. In addition, their cellular fluorescence characteristic demonstrated a potential application for imaging-guided drug delivery in tumor treatment.

Mixed surfactant modified graphene oxide nanocarriers for DOX delivery to cisplatin-resistant human ovarian carcinoma cells

Qian Zhang,Huirong Chi,Mingzhi Tang,Jiabin Chen,Guolin Li,Yushi Liu,Bing Liu

The non-covalent functionalization of graphene oxide (GO) with hydroxyethyl cellulose (HEC, nonionic surfactant) and polyanionic cellulose (PAC, anionic surfactant) was developed for anti-cancer drug delivery applications based on a nonideal mixed micelle theory of surfactants. In order to maintain the stability of GO in aqueous electrolytes, the optimal component of the mixed surfactant modified nanocarriers (GO–PAC/HEC) was determined via a multi-factors orthogonal method. Benefiting from the enormous specific surface area of GO and π–π stacking interactions, doxorubicin hydrochloride (DOX), a model anticancer drug, was loaded onto the GO–PAC/HEC surface with high drug loading. The most appropriate loading content of DOX on GO–PAC/HEC was obtained by zeta potential evaluation and a stability time test. The in vitro DOX release profiles from DOX-loaded nanocarriers (GO–PAC/HEC–DOX) exhibited a significant pH-responsive feature and satisfactory performance of drug controlled release. Moreover, in vitro investigation showed that DOX-loaded nanoparticles entered into and treated cancer cells effectively and enhanced the accumulation of DOX in SKOV3/DDP cells (cisplatin-resistant human ovarian carcinoma cell line) exhibiting higher cytotoxicity than free DOX, suggesting that DOX-loaded nanoparticles may overcome DOX resistance of SKOV3/DDP cells to some extent. Based on the results obtained in this study, GO–PAC/HEC shows considerable potential as a drug delivery vehicle.

DOX-loaded mesoporous hydroxyapatite modified by hyaluronic acid can achieve efficient targeted therapy for lung cancer

Yanjie Hu,Jisong Zhang,Liangliang Dong,Li Xu,Enguo Chen

Tumor microenvironment-responsive BSA nanocarriers for combined chemo/chemodynamic cancer therapy

Zhang Ruiyi,Liu Teng,Li Wanzhen,Ma Zhiyuan,Pei Pei,Zhang Weiwei,Yang Kai,Tao Yugui

Tumor microenvironment (TME), characterized by high glutathione (GSH), high hydrogen peroxide (H2O2) and acidic pH levels, is favorable for the growth, invasion and metastasis of cancer cells. Taking advantage of the specific characteristics of tumors, TME-responsive GCBD NPs are designed to deliver nanoscale coordination polymers (NCPs, GA-Cu) and chemotherapy drugs (doxorubicin, DOX) based on bovine serum albumin (BSA) nanocarriers into cancer cells for combined chemodynamic therapy (CDT) and chemotherapy. In an acidic environment, GCBD NPs could release approximately 90% copper ions, which can not only consume overexpressed GSH to modulate the TME but can also react with endogenous H2O2 in a Fenton-like reaction to achieve the CDT effect. Meanwhile, the released DOX could enter the nucleus of tumor cells and affect their proliferation to achieve efficient chemotherapy. Both in vitro and in vivo experiments showed that GCBD NPs had good biosafety and could effectively inhibit the growth of cancer cells. GCBD NPs are promising as a biocompatible nanoplatform to exploit TME characteristics for combined chemo and chemodynamic therapy, providing a novel strategy to eradicate tumors with high efficiency and specificity.Graphical Abstract

Gold-Aptamer-Modified Metal–Organic Framework Drug Delivery Nanosystems for Combined Photothermal/Chemotherapy of Cancer

Ting Fang,Zihao Duan,Nan Wan,Xiaoxuan Zuo,Zhongwu Pan,Weiwei Zhang,Fei Ge,Lin Gui

The poor targeting and high toxicity of chemotherapeutic drugs make them less effective against breast cancer. In this study, in accordance with their photothermal effect, the aptamer (Apt) (AS1411) and doxorubicin (DOX) were linked to zeolite imidazole salt frame8 (ZIF-8) by using gold nanorods (Au NRs). Thereby, a multifunctional targeting nanoparticle platform (DOX/Au-Apt@ZIF-8) was constructed to deliver and effectively utilize DOX and realize the antitumor effects of the multimodal combination of chemotherapy–target–photothermal therapy. This platform was responsive to both pH and near-infrared (NIR) light. In the characterization experiments, DOX/Au-Apt@ZIF-8 exhibited good dispersibility, particle size stability, and consistent spectral characteristics. The photothermal conversion efficiency was up to 53.5%. In the cell uptake and cell cycle experiments, DOX/Au-Apt@ZIF-8 effectively targeted tumor cells and blocked their growth in the S phase. Moreover, in an in vivo study, DOX/Au-Apt@ZIF-8 exerted good inhibitory effects and photothermal effects on tumors. When combined with NIR irradiation, DOX/Au-Apt@ZIF-8 inhibited tumor tissue growth by enhancing and inducing apoptosis. Importantly, histopathological analysis revealed that the nanoparticles were less toxic to other organs and had high biosafety. As such, DOX/Au-Apt@ZIF-8 fabricated in this study is expected to offer a treatment approach against breast cancer.

Controlled co-delivery nanocarriers based on mixed micelles formed from cyclodextrin-conjugated and cross-linked copolymers

Shuai Li,Qin He,Tianchan Chen,Wei Wu,Kening Lang,Zhong-Ming Li,Jianshu Li

The combination of multiple drugs within a single nanocarrier can provide significant advantages for disease therapy and it is desirable to introduce a second drug based on host–guest interaction in these co-delivery systems. In this study, a core-stabilized mixed micellar system consisting of β-cyclodextrin-conjugated poly(lactic acid)- b -poly(ethylene glycol) (β-CD-PLA-mPEG) and DL-Thioctic acid (TA) terminated PLA-mPEG (TA-PLA-mPEG) was developed for the co-delivery of DOX and fluorescein isothiocyanate labeled adamantane (FA). DOX can be loaded within the hydrophobic segment of PLA and FA may form stable complexation with β-CD in the core. The mixed micelles (MM) are based on well-accepted medical materials and can be easily cross-linked by adding 1,4-dithio- d , l -threitol (DTT), which can enhance the stability of the system. Drug-loaded MM system was characterized in terms of particle size, morphology, drug loading and in vitro release profile. Cytotoxicity test showed that blank MM alone showed negligible cytotoxicity whereas the drug-loaded MM remained relatively high cytotoxicity for HeLa cancer cells. Confocal laser scanning microscopy (CLSM) demonstrated that the MM could efficiently deliver and release DOX and FA in the same tumor cells to effectively improve drugs’ bioavailability. These results suggested that the core-stabilized MM are highly promising for intracellular co-delivery of multiple drugs.

Carboxymethyl cellulose modified graphene oxide as pH-sensitive drug delivery system

Ziqie Rao,Hongyu Ge,Liangling Liu,Chen Zhu,Lian Min,Meng Liu,Lihong Fan,Dan Li

Nanotechnology has been studied to improve drug delivery and cancer treatment. The aim of this study is to introduce amino groups into graphene oxide (GO) to form aminated fumed graphene (GO-ADH) and combine GO-ADH with carboxymethyl cellulose (CMC) to produce GO-CMC complex as a drug carrier matrix. The anti-cancer drug small molecule doxorubicin hydrochloride (DOX) was bond to GO-CMC by π-π bond interaction and hydrogen bonding to form GO-CMC/DOX drug loading system. Via the FT-IR, transmission electron microscopy (TEM) and Zeta potential analyzer analysis showed that GO-CMC complex was successfully synthesized. Studies have shown that when pH   =   5.0, the cumulative release rate of drugs can reach 65.2%, which means it has pH-sensitive ability. The cells were treated with MTT method and human cervical cancer cells (Hela cells) and mouse fibroblasts (NIH-3T3 cells). The results showed that GO-CMC had no obvious cytotoxicity and good biocompatibility.

Development of biodegradable polymeric implants of RGD-modified PEG-PAMAM-DOX conjugates for long-term intratumoral release

Ke Wang,Xiaofeng Zhang,Lihong Zhang,Lili Qian,Chang Liu,Jiajun Zheng,Yanyan Jiang

Context: The sustained release implants can be directly implanted in tumor site by surgery and are promising for cancer treatment.Objective: RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive linkage (RGD-PPCD) was a potential conjugate for tumor-targeted therapy. In order to enhance tumor retention ability and long-term effect of drug, we developed the DOX and its conjugate implants using poly(dl-lactic-co-glycolic acid) (PLGA), poly(dl-lactic acid) (PLA) and polyethylene glycol (PEG) as carrier materials.Methods: The implants were prepared by a simple solvent evaporation method. Different formulations with varying ratios of three polymers were designed, prepared and evaluated on the basis of viscosity, in vitro release and drying time. Furthermore, in vivo biodistribution and antitumor activity of the implants were studied in mice with subcutaneous C6 xenografts.Results: The optimized formulation was obtained with the 3:1 ratio of PLGA/PLA (w/w) and 1% PEG (wt.%). The drug release behavior of DOX, PPCD and RGD-PPCD implants prepared by the optimized formulation was similar according to the assessment of similarity factor f2, and the release curves were fell into three phases, including a lag-period, then the second phase which was consistent with zero-order model followed by a plateau. Data of total DOX remained in implants indicated the release were faster in vivo than in vitro. Moreover, intratumoral drug amount of RGD-PPCD implants was the highest 45 days after implantation. Correspondingly, the RGD-PPCD implants exhibited the strongest antitumor activity compared with PPCD and free DOX implants.Discussion and conclusion: This paper presents an exploratory research on macromolecule-drug conjugates, including RGD-PPCD and PPCD, which have the potential to be developed into long-term effect implants for tumor therapy with high efficiency and low systematic toxicity.

Protosappanin A Protects DOX-Induced Myocardial Injury and Cardiac Dysfunction by Targeting ACSL4/FTH1 Axis-Dependent Ferroptosis

Jingxuan Cui,Yujia Chen,Qiannan Yang,Peng Zhao,Mian Yang,Xiaoqi Wang,Ge Mang,Xiangyu Yan,Di Wang,Zhonghua Tong,Penghe Wang,Yingjin Kong,Naixin Wang,Dongni Wang,Nana Dong,Mingyang Liu,Mingyan E,Maomao Zhang,Bo Yu

Doxorubicin (DOX) is an effective anticancer agent, but its clinical utility is constrained by dose-dependent cardiotoxicity, partly due to cardiomyocyte ferroptosis. However, the progress of developing cardioprotective medications to counteract ferroptosis has encountered obstacles. Protosappanin A (PrA), an anti-inflammatory compound derived from hematoxylin, shows potential against DOX-induced cardiomyopathy (DIC). Here, it is reported that PrA alleviates myocardial damage and dysfunction by reducing DOX-induced ferroptosis and maintaining mitochondrial homeostasis. Subsequently, the molecular target of PrA through proteome microarray, molecular docking, and dynamics simulation is identified. Mechanistically, PrA physically binds with ferroptosis-related proteins acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferritin heavy chain 1 (FTH1), ultimately inhibiting ACSL4 phosphorylation and subsequent phospholipid peroxidation, while also preventing FTH1 autophagic degradation and subsequent release of ferrous ions (Fe 2+ ) release. Given the critical role of ferroptosis in the pathogenesis of ischemia-reperfusion (IR) injury, this further investigation posits that PrA can confer a protective effect against IR-induced cardiac damage by inhibiting ferroptosis. Overall, a novel pharmacological inhibitor is unveiled that targets ferroptosis and uncover a dual-regulated mechanism for cardiomyocyte ferroptosis in DIC, highlighting additional therapeutic options for chemodrug-induced cardiotoxicity and ferroptosis-triggered disorders.

The Fabrication of rGO/(PLL/PASP)3@DOX Nanorods with pH-Switch for Photothermal Therapy and Chemotherapy

Xiangming Li,Yihe Zhang,Zequn Ma,Meng Fu,Qi An

Graphical The heat is on : A facile and efficient approach for the preparation of pH responsive self-assembled (electrostatic interactions) rGO-polymer-DOX nanocomposites for photothermal and chemical therapy is reported (see figure). The development of well-controlled drug carriers that are stable and highly effective for the delivery of anticancer agents is challenging. Herein, we report a novel pH-controlled drug delivery system, utilizing reducing graphene oxide (rGO)-polymer self-assembly films as carriers, for the preparation of effective drug nanorods and nanoparticles. In this system, the rGO-polymer carriers were constructed by the alternating assembly of poly- l -lysine (PLL) and polyaspartic acid (PASP) around the rGO sheets. Furthermore, the rGO-polymer cores, which possess a positively charged surface as the desired template, could assemble with negatively charged doxorubicin (DOX) via electrostatic interactions. The DOX embedding efficiency and the morphology of the drug nanocomposites could be controlled by the number of rGO-polymer bilayers and concentration of the rGO-polymer bilayers and the initial DOX concentration. Importantly, the release of DOX could be regulated by controlling the pH and by using a NIR laser. Under acidic conditions, the interactions between the PASP layer and DOX molecules can be broken, resulting in gradual release of the DOX molecules. Upon NIR irradiation, the release of DOX could be further accelerated and a photothermal effect from rGO induced. Cellular uptake and cytotoxicity experiments indicate that the drug nanocomposites possess effective anticancer activity. Thus, in this work, we present a useful strategy for the fabrication of pH-responsive drug nanocomposites for combined photothermal and chemical therapy. The nanocomposite can be used as a potential drug delivery system for practical cancer treatment.

Synthesis of a GNRs@mSiO2-ICG-DOX@Se-Se-FA Nanocomposite for Controlled Chemo-/Photothermal/Photodynamic Therapy

Na An,Huiming Lin,Fengyu Qu

Graphical GNRs@mSiO 2 core–shell nanoparticles have been synthesized as host to load ICG and DOX molecules by the layer-by-layer assembly method through electrostatic interactions. A sensitive Se–Se linker was synthesized and grafted to ensure controlled release. Under NIR irradiation, the enhanced cytotoxicity to cancer cells is derived from the synergistic effect of chemotherapy, PTT, and PDT. A novel GNRs@mSiO 2 core–shell nanocomposite has been synthesized to integrate sensitive chemotherapy with photodynamic therapy (PDT) and photothermal therapy (PTT) for enhanced antitumor treatment by using gold nanorods (GNRs) as the core and mesoporous silica (mSiO 2 ) as the shell. After modifying with -NH 2 , Indocyanine Green (ICG, negative charge) and doxorubicin hydrochloride (DOX, positive charge) molecules could be stored in the mesopores by the layer-by-layer assembly method through electrostatic interactions. To inhibit leakage from the mesopores, a sensitive Se–Se linker was synthesized and adopted as a nanovalve coated on the outside of the nanoparticles (GNRs@mSiO 2 -ICG-DOX@Se-Se). Under NIR (808 nm) irradiation, heat elevation (derived from GNR/ICG) and generation of reactive oxygen species (ROS, derived from ICG) can also be detected in vitro. Owing to the redox sensitivity of Se–Se, GNRs@mSiO 2 -ICG-DOX@Se-Se showed reduction (GSH)- as well as oxidation (ROS)-triggered DOX release. To further ensure specific targeting, folic acid (FA) was grafted to the outside of the nanoparticles, because of the high expression of FA receptors on tumor cells. Detailed cell experiments performed with the nanoparticles and HepG2 as typical cancer cells showed enhanced cytotoxicity towards the cancer cells owing to the synergistic effect of chemotherapy, PTT, and PDT. On account of the different GSH concentrations in cancer and normal cells and the switch-on/off application of NIR irradiation, the GNRs@mSiO 2 -ICG-DOX@Se-Se-FA nanoparticles show potential for applications in cancer therapy.