查找使用阿拉丁产品的科研文献

Enzyme/pH dual stimuli-responsive nanoplatform co-deliver disulfiram and doxorubicin for effective treatment of breast cancer lung metastasis

Peifu Xiao,Xiaoguang Tao,Hanxun Wang,Hongbing Liu,Yupeng Feng,Yueqi Zhu,Zhengzhen Jiang,Tian Yin,Yu Zhang,Haibing He,Jingxin Gou,Xing Tang

Reprogramming dysfunctional dendritic cells by a versatile metabolism nano-intervenor for enhancing cancer combinatorial immunotherapy

Jie Yang,Xiuhua Pan,Jun Zhang,Siyu Ma,Jianeng Zhou,Zengguang Jia,Yawen Wei,Zengyi Liu,Ning Yang,Qi Shen

Dendritic cells (DCs) are crucial for the orchestration of anti-tumor immune response. However, the immunosuppressive cholesterol metabolism of DCs in tumor sites induces dysfunction of DCs and limited antigen presentation . Herein, a metabolism nano-intervenor of DCs (Man-OVA(RSV) NPs) was loaded in a versatile hydrogel system ( [email protected] ) based on the gelation reaction between graphene oxide (GO) and metformin hydrochloride (MET). The nanoparticle packaged rosuvastatin (RSV) interfered with cholesterol metabolism of DCs to reduce antigen degradation, thereby enhancing antigen presentation. Due to the DC targeting ability of mannose decoration on NPs and durable releasing profiles of hydrogel, the system achieved precise and long-term immunometabolism intervention of DCs. Moreover, reprogramming metabolism of DCs could significantly restore the efficacy of DC-mediated immunotherapy and combine with immune-checkpoint inhibition induced by MET to significantly improve therapeutic outcomes. Collectively, reprogramming cholesterol metabolism of DCs may be a potential strategy to ameliorate the malfunctional DCs and evoke robust anti-tumor immunity.

Size-changeable nanoprobes for the combined radiotherapy and photodynamic therapy of tumor

Hou Zhenyu,Zhou Mei,Ma Yuanyuan,Xu Xiaoxuan,Zhang Zhiqi,Lai Shiwei,Fan Wenpei,Xie Jinbing,Ju Shenghong

Purpose Radiation therapy (RT) and photodynamic therapy (PDT) are promising while challenging in treating tumors. The potential radiation resistance of tumor cells and side effects to healthy tissues restrict their clinical treatment efficacy. Effective delivery of therapeutic agents to the deep tumor tissues would be available for tumor-accurate therapy and promising for the tumor therapy. Thus, developing nanoprobes with effectively delivering radiotherapy sensitizers and photosensitizers to the interior of tumors is needed for the accurate combined RT and PDT of tumor. Methods The size-changeable nanoprobes of Gd 2 O 3 @BSA-BSA-Ce6 (BGBC) were synthesized with a crosslinking method. Magnetic resonance imaging (MRI) and in vivo near-infrared (NIR) imaging were measured to evaluate the nanoprobes’ tumor accumulation and intratumor penetration effect. The tumor suppression effect of combined RT and PDT with these nanoprobes was also studied for the 4T1 bearing Balb/c mice. Results The nanoprobes BGBC showed high tumor accumulation and disintegrated into small particles responding to the photo-irradiation-produced reactive oxygen species (ROS), allowing for tumor penetration. Abundant radiotherapy sensitizers and photosensitizers were delivered to the deep tumor tissues, which is available for the accurate therapy of tumor. In addition, the BGBC displayed outstanding MRI and fluorescence imaging effects for evaluating the biodistribution and tumor suppression effect of nanoprobes. Consequently, significant tumor suppression effect was obtained based on the accurate tumor treatment with the combined RT and PDT. Conclusion The designed size-changeable nanoprobes BGBC showed excellent tumor accumulation and deep tumor penetration, resulting in a significant tumor suppression effect based on the combined RT and PDT. This study provides a novel strategy for dual delivery of radiotherapy sensitizers and photosensitizers into the deep tumor tissues and is promising for the accurate theranostics of tumor.

Tumor-derived exosomes reversing TMZ resistance by synergistic drug delivery for glioma-targeting treatment

Ruoning Wang,Qifan Liang,Xinru Zhang,Zhenning Di,Xiaohong Wang,Liuqing Di

Temozolomide (TMZ), as the first-line chemotherapeutic agent, relies on inducing DNA methylation of O 6 -guanine for treating glioma. However, the survival time of patients are hardly exceeded 14.5 months, attributing to inevitable drug resistance and systematic toxicity after long-term administration. Herein, reassembly-exosomes (R-EXO) deriving from homologous glioma cells is proposed to carry TMZ and Dihydrotanshinone (DHT) for reversing drug resistance and enhancing lesions-targeted drug delivery, defined as R-EXO-TMZ/DHT (R-EXO-T/D). It is found that R-EXO-T/D share various advantages, including preferable blood-brain barrier (BBB)-penetrating ability with nanomemter size, tumor-homing accumulation with homologous effects, as well as potentiated antitumor activity with overcoming TMZ resistance and triggering immune response. This work develops a new strategy for site-specific drug delivery, showing a promising application of drug compatibility in glioma treatment.

A Nanopipette Supported Oil/Water Interface Sensor for the Kinetics Analysis and Determination of Phenothiazine Derivatives

Yongtao You,Silan Bai,Yamin Ma,Cheng Liu,Lishi Wang

ABSTRACT Phenothiazine is an intermediate in the synthesis of drugs, and its derivatives, i.e., chlorpromazine (CPZ) and promethazine (PMZ), are both the major tranquilizers. Herein, a nanoscale soft sensor constructed utilizing the interface between two immiscible electrolyte solutions (ITIES) for CPZ and PMZ drugs was introduced. A nanopipette with a 60 nm diameter orifice was used to support the ITIES , and voltammetry and amperometry were used for the qualitative and quantitative determination of these two drugs crossing the liquid/liquid (L/L) interface. Half-wave potentials ( Δ w o φ 1 / 2 ${\Delta }_w^o{\phi }_{1/2}$ ) of 0.107 V and 0.092 V (vs. Δ w o φ 1 / 2 , T E A + ${\Delta }_w^o{\phi }_{1/2,TEA+}$ ) for PMZ + and CPZ + transfer from water to 1,2-dichloroethane (DCE) were obtained, respectively. Subsequently, the kinetics and effective hydrophilicity of these two drugs were thoroughly investigated. Moreover, there were two calibration curves for the determination results between the current and the concentration range for CPZ + and PMZ + by cyclic voltammetry (the concentrations range from 0.1 to 10 mmol −1 ) and amperometry (the concentrations range from 0.02 to 10 mmol −1 ). Finally, the actual drug recovery for these two drugs ranged from 94.83% to 111.02%, which indicates the accuracy in actual medicine is good. The above work provides a soft nano-liquid/liquid interfacial sensor with applications in drugs, including kinetics studies and drug determination, and many applications in detecting pharmaceutical molecules, cellular secretion and other bioorganic compounds.

ROS responsive polyethylenimine-based fluorinated polymers for enhanced transfection efficiency and lower cytotoxicity

Peng Hua,Donglin Yang,Ruie Chen,Peiqi Qiu,Meiwan Chen

Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity, while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF 12.5%, TKPF 25%, and TKPF 50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions. The fluorophilic effect mediated efficient cellular uptake and endosomal escape while ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. TKPFs also exhibited great serum resistance in gene delivery and TKPF 50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrate that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.

Sulfuric-acid-mediated synthesis strategy for multi-colour aggregation-induced emission fluorescent carbon dots: Application in anti-counterfeiting, information encryption, and rapid cytoplasmic imaging

Lijuan Yang,Shaochi Liu,Tian Quan,Yongqing Tao,Meng Tian,Luchun Wang,Junji Wang,Dandan Wang,Die Gao

Aggregation-induced emission fluorescent carbon dots (AIE-CDs) have applications in the fields of multi-colour anti-counterfeiting, information encryption, and imaging. In this study, four AIE-CDs (B-AIE-CDs, G-AIE-CDs, Y-AIE-CDs, and O-AIE-CDs) with blue, green, yellow, and orange fluorescence at high concentrations were fabricated using crystal violet as a precursor, solutions with different sulfuric acid concentrations as solvents under different temperatures and reaction times for the first time. The structural properties and fluorescence behaviour of the AIE-CDs were investigated. The results revealed that the sulfuric acid concentration had a significant effect on the fluorescence colour of the AIE-CDs because sulfuric acid can affect the degree of carbonisation, the type and content of nitrogen. Moreover, the reaction temperature and time affected the surface-defect state and the degree of carbonisation of the AIE-CDs, which affected the emission wavelength and quantum yield (QY) of the AIE-CDs. Furthermore, to exploit the unique characteristics (polychromatic aggregation fluorescence and acid-sensitive properties) of the obtained-AIE-CDs, anti-counterfeiting and information encryption methodologies (i.e., acid-stimuli-response producing multi-colour fluorescence) were preliminarily developed. Finally, B-AIE-CDs with a high QY of 43.5% were successfully used for rapid cytoplasmic imaging, demonstrating their applicability in biological fields.

Structure–activity relationships of pH-responsive and ionizable lipids for gene delivery

Yu Zou,Quan Zhou,Yinan Zhao,Defu Zhi,Huiying Chen,Rui Wang,Benzhi Ju,Shubiao Zhang

Ionizable lipids are the leading vectors for gene therapy. Understanding the effects of molecular structure on efficient gene delivery is one of the most important challenges for maximizing the utility of such lipid vectors. We synthesized an array of pH-responsive and ionizable lipids to investigate the relationship between lipid structure and activity. The optimized lipid (EDM) has double tertiary amines in the headgroup and an ester linker. EDM exhibited efficient DNA and siRNA delivery to, and gene silencing of, A549 cells. EDM has a p K a value of 6.67, which enabled it to quickly escape from the endosome after entering the cell; the ester linkages rapidly degraded and enabled gene release into the cytoplasm. EDM also delivered IGF-1R siRNA to inhibit tumor growth and induce cancer cell apoptosis by efficient inhibition of IGF-1R expression in mice. Our study on the structure–activity relationships of ionizable lipids will facilitate clinical applications.

DPA-Zinc around Polyplexes Acts Like PEG to Reduce Protein Binding While Targeting Cancer Cells

Xuan Nie,Wei You,Ze Zhang,Fan Gao,Xiao-Hong Zhou,Hai-Li Wang,Long-Hai Wang,Guang Chen,Chang-Hui Wang,Chun-Yan Hong,Qi Shao,Fei Wang,Lei Xia,Yang Li,Ye-Zi You

Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine-zinc (DPA-Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape.

ROS-responsive fluorinated polyethyleneimine vector to co-deliver shMTHFD2 and shGPX4 plasmids induces ferroptosis and apoptosis for cancer therapy

Suleixin Yang,Ka Hong Wong,Peng Hua,Chengwei He,Hua Yu,Dan Shao,Zhi Shi,Meiwan Chen

Ferroptosis is a newly discovered non-apoptotic cell death form but its therapeutic efficacy triggered by traditional iron-based nanomaterials or classic drug inducers has been far from satisfactory due to the high glutathione (GSH) level in cancer cells and insufficient lipid peroxide production. Here we reported a ferroptosis/apoptosis combinational therapy by depleting GSH and downregulating GPX4 to disrupt redox homeostasis and amplify ferroptosis-related oxidation effect. In this study, we developed reactive oxygen species (ROS)-responsive serum-resistant nanoparticles with thioketal-crosslinked fluorinated polyethyleneimine 1.8K ( TK PF) as the core, which were wrapped with hyaluronic acid (HA) as the shell ( TK PFH NP) to co-deliver shGPX4 and shMTHFD2 plasmids for cancer treatment. The highly efficient and tumor-selective gene carrier TK PFH NPs revealed outstanding transfection efficiency (∼100 %) and sustained the efficiency (∼50 %) even in media containing 90 % FBS. Mediated by HA, TK PFH NPs actively targeted CD44 receptors, thus enabling efficient uptake by tumor cells and experiencing surface charge conversion to induce subsequent lysosomal escape. Then the TK PF NPs were effectively disintegrated by the abundant ROS in cancer cells, which facilitated the release of plasmids and avoided the cytotoxicity of cationic polymers. shGPX4 plasmid induced ferroptosis by producing ROS and lipid peroxides via downregulating GPX4, while shMTHFD2 triggered apoptosis by modulating NADPH/NADP and depleting GSH of the cancer cells. Moreover, GSH consumption caused by shMTHFD2 indirectly suppressed GPX4 and further augmented ferroptosis, showing synergistic anticancer effect against B16-F10 cells. Taken together, the rationally designed dual-gene loaded TK PFH NPs provided a safe and high-performance platform for enhanced ferroptosis-apoptosis combined anticancer efficacy based on gene therapy. Statement of significance The therapeutic efficacy of ferroptosis has been far from satisfactory due to high GSH level and insufficient lipid peroxide production in cancer cells. Herein, we reported a ferroptosis/apoptosis combinational therapy by depleting GSH and downregulating GPX4 to disrupt redox homeostasis and amplify ferroptosis-related oxidation effect. ROS-responsive serum-resistant nanoparticles were fabricated with thioketal-crosslinked fluorinated PEI 1.8K ( TK PF) as the core and hyaluronic acid (HA) as the shell ( TK PFH NP) to co-deliver shGPX4 and shMTHFD2 plasmids. The shGPX4 plasmid induced ferroptosis by producing ROS and lipid peroxides via downregulating GPX4, while shMTHFD2 triggered apoptosis by modulating NADPH/NADP and depleting GSH. The rationally designed dual-gene loaded TK PFH NPs provided a safe and high-performance platform aimed for enhanced ferroptosis-apoptosis combined anticancer efficacy.

Glycyrrhiza acid-Licochalcone A complexes for enhanced bioavailability and anti-melanogenic effect of Licochalcone A: cellular uptake and in vitro experiments

Zhuxian Wang,Yaqi Xue,Quanfu Zeng,Zhaoming Zhu,Yuan Wang,Yufan Wu,Chunyan Shen,Hongxia Zhu,Cuiping Jiang,Li Liu,Qiang Liu

Licochalcone A (LicA) is a natural chalcones , well-known for its anti-melanogenic activity, however, its poor solubility leads to a limited topical bioavailability and clinical outcomes. Therefore, LicA-encapsulated glycyrrhiza acid (GA) (GA-LicA) micelles were formulated for higher cellular uptake and improved cutaneous applications. The physicochemical properties (morphology, size and charge), topical penetration, endocytic pathways, cellular uptake amount (CUA) and intracellular distribution of the GA-LicA micelles were studied. Moreover, the anti-melanogenic mechanisms including antioxidant properties, melanogenesis-mediated enzymes and melanin generation as well as cell apoptosis in A375 cells were demonstrated. We found that significant increase amount of LicA was obtained into the epidermis after encapsulated in GA micelles, and the hair follicles were the preferential route for LicA permeation. Moreover, HaCaT and melanocytes possessed a significantly higher effective uptake and CUA for GA-LicA micelles than that of the crude LicA. Caveolae-mediated and actin filaments-mediated endocytosis, caveolae-mediated endocytosis were respectively involved in cellular uptake of GA-LicA micelles for HaCaT cells and melanocytes. Furthermore, GA-LicA micelles possessed a synergistic anti-melanogenic effect by scavenging the free radicals, reducing the activity of α-glucosidase and tyrosinase , and inducing the cell apoptosis. Taken together, GA micelles can enhance the bioavailability and anti-melanogenic effect of LicA, and the article provided principles for rational design of formulations in whitening cosmetics.

Preparation of a Self-Assembled Rhein–Doxorubicin Nanogel Targeting Mitochondria and Investigation on Its Antihepatoma Activity

Li Wu,Yan Shi,Zihui Ni,Tao Yu,Zhipeng Chen

Mitochondria are involved in the regulation of apoptosis, making them a promising target for the development of new anticancer drugs. Doxorubicin (DOX), a chemotherapeutic drug, can induce reactive oxygen species (ROS)-mediated apoptosis, improving its anticancer effects. Herein, Rhein, an active ingredient in rhubarb, with the capability of self-assembly and mitochondrial targeting, was used in conjunction with DOX to form efficient nanomaterials (Rhein–DOX nanogel) capable of sustained drug release. It was self-assembled with a hydrogen bond, π–π stacking interactions, and hydrophobic interactions as the main driving force, and its loading efficiency was up to 100%. Based on its self-assembly characteristics, we evaluated the mechanism of this material to target mitochondria, induce ROS production, and promote apoptosis. The IC50 of the Rhein–DOX nanogel (3.74 μM) was only 46.3% of that of DOX (11.89 μM), and the tumor inhibition rate of the Rhein–DOX nanogel was 79.4% in vivo, 2.3 times that of DOX. This study not only addresses the disadvantages of high toxicity of DOX and low bioavailability of Rhein, when DOX and Rhein are combined for the treatment of hepatoma, but it also significantly improved the synergistic antihepatoma efficacy of Rhein and DOX, which provides a new idea for the development of long-term antihepatoma agents with low toxicity.