Pharmaceutics
·
2026
·Vol. 18
·期 7
·872
·
IF 6.9
Weinan Li,Sisi Yan,Yingying Gao,Yuhan Fu,Yutong Mei,Yanhong Wang,Zhixin Yang
Background: The highly heterogeneous and dynamically evolving tumor microenvironment leads to the development of drug resistance and recurrence in traditional therapies. Although immunotherapy demonstrates unique advantages, its clinical utility remains constrained by the suboptimal immunogenicity and the limited effect of monotherapy. Herein, a hybrid drug delivery system based on a spatiotemporal hierarchical controlled-release strategy was proposed to achieve dual immunotherapy with immune checkpoint blockade (ICB) and immunogenic cell death (ICD) to promote synergistic anti-tumor therapy.Methods: A liposome–micelle hybrid drug delivery system (RUT-RPP-LP) was constructed using a lipid bilayer composed of dioleoyl phosphatidylethanolamine/hemisuccinyl cholesterol to encapsulate rutin (RUT) and to form an inner cavity-encapsulated resveratrol micelle (RPP). RUT-RPP-LP was characterized, and its pH sensitivity and release behavior were investigated. Subsequently, a colon cancer tumor-bearing mouse model was constructed to evaluate the in vivo targeted anti-tumor effect and biological safety. On this basis, the combined mechanism of ICB and ICD was preliminarily explored.Results: RUT-RPP-LP possessed excellent formulation characteristics, stability, and biocompatibility, achieving graded controlled release of drugs via responding to the TME and lysosomal acidity, respectively. Obviously, RUT-RPP-LP could specifically target the tumor site, induce the occurrence of ICD, and simultaneously block the PD-1/PD-L1 immune checkpoint signaling pathway, thereby enhancing the function of T cells and inducing apoptosis of tumor cells.Conclusions: The RUT-RPP-LP based on the hierarchical controlled-release strategy exerted a spatiotemporally coordinated enhancement of anti-tumor immunity, and may provide a novel combinatorial approach to overcome the low response of immunotherapy in solid tumors.
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高影响因子
JOURNAL OF POLYMER SCIENCE
·
2023
·Vol. 61
·期 12
·1111-1119
·
IF 3.4
Yajun Xu,Jianlin Lv,Chaoying Kong,Yanran Li,Kun Wang,Na Shen,Zhaohui Tang
Tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-dioxide), a representative hypoxia-activated prodrugs (HAPs), has entered Phase II/III clinical trials. Despite a promising phase II clinical trial results, TPZ does not bring benefits to cancer therapy in most phase III clinical trials, which making the clinical trials failed. To improve its therapeutic effects, in this study, we synthesize a novel TPZ derivative, 3-(3-(5-hydroxypentyl)ureido)benzo[e][1,2,4]triazine 1,4-dioxide (TPZH), and covalently conjugated it to poly (L-glutamic acid) (PLG) to obtain TPZH nanoparticles (TPZH-NPs). The TPZH-NPs shows prolonged blood circulation, enhanced tumor accumulation, and increased maximum tolerated dose (MTD) than TPZH. In addition, TPZH-NPs exhibits significantly enhanced antitumor therapeutic efficiency than free TPZH against 4T1 breast tumors. Graphical
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ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Jiaojiao Zhu,Man Guo,Yanhui Cui,Yingcai Meng,Jinsong Ding,Wenbin Zeng,Wenhu Zhou
Pulmonary delivery of anti-inflammatory siRNA presents a promising approach for localized therapy of acute lung injury (ALI), while polycationic vectors can be easily trapped by the negatively charged airway mucin glycoproteins and arbitrarily internalized by epithelial cells with nontargetability for immunological clearance. Herein, we report a material, the dopamine (DA)-grafted hyaluronic acid (HA–DA), coating on an anti-TNF-α vector to address these limitations. HA–DA was simply synthesized and facilely coated on poly(β-amino ester) (BP)-based siRNA vectors via electrostatic attraction. The resulting HA–DA/BP/siRNA displayed significantly enhanced mucus penetration, attributable to the charge screen effect of HA–DA and the bioadhesive nature of the grafting DA. After transmucosal delivery, the nanosystem could target diseased macrophages via CD44-mediated internalization and rapidly escape from endo/lysosomes through the proton sponge effect, resulting in effective TNF-α regulation. Meanwhile, DA modification endowed the coating material with robust antioxidative capability to scavenge a broad spectrum of reactive oxygen/nitrogen species (RONS), which protected the lung tissue from oxidative damage and synergized with anti-TNF-α to inhibit a cytokine storm. As a result, a remarkable amelioration of ALI was achieved in a lipopolysaccharide (LPS)-stimulated mice model. This study provides a multifunctional coating material to facilitate pulmonary drug delivery for the treatment of lung diseases.
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高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 9
·4236-4245
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IF 3.591
Jia Zhang,Jian Yang,Junying Tian,Hailong Liu,Xuemei Li,Weiguo Fang,Xun Hu,Chungu Xia,Jing Chen,Zhiwei Huang
The synthesis of useful amines from bio-based carbonyl compounds is highly desired owing to their mild reaction conditions and green sustainability. The reductive amination of bio-furfural-derived 2-hydroxytetrahydropyran (2-HTHP) to high-value-added 5-Amino-1-pentanol (5-AP) was carried out over efficient Ni–Al2O3 catalysts prepared by a co-precipitation method. Among the Ni–Al2O3 catalysts with different Ni loadings (0–100 wt%) tested, the 50Ni–Al2O3 catalyst exhibited the highest 5-AP yield of 91.3% under mild conditions of 60 °C and 2 MPa H2. This catalyst also presented good stability during a 150 h time-on-stream without appreciable deactivation. Characterization results showed that the 50Ni–Al2O3 catalyst exhibited small Ni0 nanoparticles (5.5 nm), a high reduction degree (up to 95%), and a large amount of strong Lewis acid sites. The cooperative catalysis of the strong Lewis acid sites and highly dispersed metallic Ni sites is suggested to play an important role in achieving high efficiency in 2-HTHP reductive amination.
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CHINESE JOURNAL OF CATALYSIS
·
2020
·
IF 6.146
Xuemei Li,Junying Tian,Hailong Liu,Congkui Tang,Chungu Xia,Jing Chen,Zhiwei Huang
A highly efficient and green process was developed for the synthesis of useful 5-amino-1-pentanol (5-AP) from biomass-derived dihydropyran by coupling the in situ generation of 5-hydroxypentanal (5-HP, via the ring-opening tautomerization of 2-hydroxytetrahydropyran (2-HTHP)) and its reductive amination over supported Ni catalysts. The catalytic performances of the supported Ni catalysts on different oxides including SiO 2 , TiO 2 , ZrO 2 , γ-Al 2 O 3 , and MgO as well as several commercial hydrogenation catalysts were investigated. The Ni/ZrO 2 catalyst presented the highest 5-AP yield. The characterization results of the oxide-supported Ni catalysts showed that the Ni/ZrO 2 catalyst possessed high reducibility and a high surface acid density, which lead to the enhanced activity and selectivity of the catalyst. The effect of reaction parameters on the catalytic performance of the Ni/ZrO 2 catalyst was studied, and a high 5-AP yield of 90.8% was achieved in the reductive amination of 2-HTHP aqueous solution under mild conditions of 80 °C and 2 MPa H 2 . The stability of the Ni/ZrO 2 catalyst was studied using a continuous flow reactor, and only a slight decrease in the 5-AP yield was observed after a 90-h time-on-stream. Additionally, the reaction pathways for the reductive amination of 2-HTHP to synthesize 5-AP were proposed.
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ACS Sustainable Chemistry & Engineering
·
2020
·
IF 7.632
Xuemei Li,Junying Tian,Hailong Liu,Xun Hu,Jia Zhang,Chungu Xia,Jing Chen,Haichao Liu,Zhiwei Huang
The reductive amination (RA) of 2-hydroxytetrahydropyran (2-HTHP) produced from biofurfural-derived dihydropyran provides a new efficient process for the clean synthesis of valuable 5-amino-1-pentanol (5-AP). Among various solid catalysts tested, the inexpensive Ni–Mg3AlOx catalysts derived from hydrotalcite precursors were found to be very active and selective, especially at Ni loadings above 20 wt %. A 85% total yield of 5-AP was obtained from dihydropyran on 40Ni–Mg3AlOx, the catalyst with the highest 2-HTHP RA activity among the Ni–Mg3AlOx catalysts, under mild conditions of 60 °C and 2 MPa H2. Characterization results showed that the reducibility of the calcined NiO-Mg3AlOx samples increased with increasing Ni loading from 5 to 50 wt %, while the Ni0 crystallite sizes exhibited a minimum of 4.8 nm on 40Ni–Mg3AlOx after reduction in H2 at 750 °C. The volcanic changes of 5-AP generation rate/yield with increasing Ni loading of the Ni–Mg3AlOx catalysts and with rising prereduction temperature of 30Ni–Mg3AlOx catalyst in 2-HTHP RA indicate that the balance of the reducibility and Ni0 particle size of the catalysts played an important role in obtaining high 5-AP yields. The 30Ni–Mg3AlOx catalyst showed a good stability in 2-HTHP RA examined in a continuous flow reactor over a 90 h time-on stream.
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International Journal of Nanomedicine
·
2020
·
IF 5.115
Hao Zhou,Zhiwen Qi,Xingying Xue,Chengzhang Wang
Purpose The aim of this study was to develop a means of improving the bioavailability and anticancer activity of urushiol by developing an urushiol-loaded novel tumor-targeted micelle delivery system based on amphiphilic block copolymer poly(ethylene glycol)-b-poly-(β-amino ester) (mPEG-PBAE).Materials and Methods We synthesized four different mPEG-PBAE copolymers using mPEG-NH2 with different molecular weights or hydrophobicity levels. Of these, we selected the mPEG5000-PBAE-C12 polymer and used it to develop an optimized means of preparing urushiol-loaded micelles. Response surface methodology was used to optimize this formulation process. The micellar properties, including particle size, pH sensitivity, drug release dynamics, and critical micelle concentrations, were characterized. We further used the MCF-7 human breast cancer cell line to explore the cytotoxicity of these micelles in vitro and assessed their pharmacokinetics, tissue distribution, and antitumor activity in vivo.Results The resulting micelles had a mean particle size of 160.1 nm, a DL value of 23.45%, and an EE value of 80.68%. These micelles were found to release their contents in a pH-sensitive manner in vitro, with drug release being significantly accelerated at pH 5.0 (98.74% in 72 h) without any associated burst release. We found that urushiol-loaded micelles were significantly better at inducing MCF-7 cell cytotoxicity compared with free urushiol, with an IC50 of 1.21 mg/L. When these micelles were administered to tumor model animals in vivo, pharmacokinetic analysis revealed that the total AUC and MRT of these micelles were 2.28- and 2.53-fold higher than that of free urushiol, respectively. Tissue distribution analyses further revealed these micelles to mediate significantly enhanced tumor urushiol accumulation.Conclusion The pH-responsive urushiol-loaded micelles described in this study may be ideally suited for clinical use for the treatment of breast cancer.
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高影响因子
CATALYSIS LETTERS
·
2022
·Vol. 153
·期 9
·2813-2823
·
IF 2.936
Yang Jian,Li Xuemei,Zhang Jia,Tian Junying,Yao Xiaolan,Liu Hailong,Xia Chungu,Huang Zhiwei
Valuable 5-amino-1-pentanol (5-AP) was efficiently synthesized from biomass-derived dihydropyran over hydroxylapatite nanorod supported Ni catalysts (Ni-HAP), by coupling the in situ generation of 5-hydroxypentanal (5-HP, via the ring-opening tautomerization of 2-hydroxytetrahydropyran (2-HTHP)) and its subsequent reductive amination. The Ni-HAP catalyst with 10 wt% Ni loading exhibited the highest 5-AP yield than the other Ni-HAP catalysts with different Ni loadings and several commercial hydrogenation catalysts, including Ru/C, Pt/C and Pd/C, as well as Raney Ni. High Ni particles dispersion, high reducibility and acidic intensity were found to account for the superior catalytic performance of 10Ni-HAP. The effect of reaction parameters on the catalytic performance was investigated, and an excellent 5-AP yield of 92% was achieved under mild reaction conditions of 80 °C and 2 MPa H 2 . The stability of the Ni-HAP catalyst was studied using a continuous flow reactor, and the sintering of Ni nanoparticles was considered as the major reason for the decline in hydrogenation activity. Graphical Abstract The Ni-HAP catalyst exhibited high catalytic performance to synthesis 5-AP due to the high Ni particles dispersion, reducibility and acidic intensity.
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ACS Nano
·
2023
·
IF 17.1
Huahai Yu,Ying Piao,Yifan Zhang,Jiajia Xiang,Shiqun Shao,Jianbin Tang,Zhuxian Zhou,Youqing Shen
Effective accumulation and penetration of antibiotics in the biofilm are critical issues for bacterial infection treatment. Red blood cells (RBCs) have been widely utilized to hitchhike nanocarriers for drug delivery. It is vital and challenging to find a nanocarrier with an appropriate affinity toward RBCs and bacteria for selective hitchhiking and release that determines the drug delivery efficiency and specificity. Herein, we report a zwitterionic polymer poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate) (OPDEA)-based micelle, which can hitchhike on RBCs in blood and preferentially release in the infection site. We found that OPDEA could bind to the RBCs cell membrane via phospholipid-related affinity and transfer to Gram-positive bacteria due to nearly an order of magnitude stronger interaction with the bacteria cell wall. The zwitterionic surface and cell-wall affinity of OPDEA-based micelles also promote their penetration in biofilm. The clarithromycin-loaded OPDEA micelles show efficient drug delivery into the infection site, resulting in excellent therapeutic performance in both peritonitis and pneumonia models by intravenous or spray administration. This simple RBC-selective hitchhiking and releasing antibiotic delivery system provides a promising strategy for the design of antibacterial nanomedicines.
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Arabian Journal of Chemistry
·
2023
·
IF 6
Hua Yuan,Changwei Zhang,Peng Zhou,Xiaoran Yang,Ran Tao,Jianzhong Ye,Chengzhang Wang
Lacking of substantial physiological activity and low utilization remains a problem for most conventional drug carriers. Polyprenol with beneficial medical effects and high availability could be an ideal candidate for solving this issue. Here, Ginkgo biloba leaves polyprenol (GBP)-based derivative was prepared by Michael addition reaction of poly (β-amino esters) (PBAE) with GBP and galactose (Gal). The intervention of poly (β-amino ester) and galactose promoted GBP-PBAE-Gal to depict as micellar carrier, enhancing the loading of hydrophobic DOX and the sensitivity to the specific tumor microenvironment, with the largest DOX loading of 28.62 ± 1.49 % and the efficient DOX release rate of 90.30 %. In the meantime, GBP-PBAE-Gal exhibited enhanced colloidal stability at 640-folds of dilution and in the presence of serum and realized the possibility of long-term storage at room temperature. Additionally, GBP-PBAE-Gal was safe for human red blood cells and human normal liver cells HL-7702. When applied for DOX delivery to HepG2 cells, GBP-PBAE-Gal increased the targeting of DOX to intensify its inhibition on HepG2 cells. Compared to free DOX, the DOX loaded into GBP-PBAE-Gal presented stronger anticancer activity, with IC 50 of 0.56 μg/mL at 72 h. Besides, the anticancer mechanism study revealed that GBP-PBAE-Gal arrested the cell cycle in HepG2 cells, suggesting the potential of GBP-based carrier for intensive treatment. This research evidenced the feasibility and high availability of the GBP to use as a drug carrier, providing a novel candidate for drug delivery systems.
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Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 45
·7521-7529
·
IF 4.776
Hong Xiao,Jin He,Xiaoxia Li,Bo Li,Lu Zhang,Yong Wang,Du Cheng,Xintao Shuai
Multidrug resistance (MDR) is one of the major obstacles hindering the successful chemotherapy of cancer. Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) is an important factor responsible for MDR. In this study, a novel copolymer methoxy-poly(ethylene glycol)–poly[(N-(6-hydroxyhexyl)-g-doxorubicin-L-aspartamide)-(β-benzyl-L-aspartate)] (mPEG-P[Asp(HPA-g-DOX)-BLA)] was synthesized and utilized to assemble into nanovesicles with hydrophilic P-gp inhibitor elacridar hydrochloride (Ela) encapsulated into the aqueous lumen. Doxorubicin (DOX) was covalently conjugated onto the polymer chain via a pH-cleavable amide linkage, leading to a pH responsive DOX release as well as disintegration of the nanovesicles in the lysosome of tumor cells. In vitro studies demonstrated that the DOX and Ela co-delivered nanovesicles showed superior cytotoxicity and enhanced anti-tumor properties as compared to single DOX-delivery nanosystems in MCF-7/ADR cancer, which was attributed to the P-gp bioactivity inhibition as investigated by a cell immunofluorescence assay. In vivo studies showed that the polymeric nanovesicles effectively accumulated at the tumor site and the co-delivered DOX and Ela effectively suppressed the MCF-7/ADR tumor growth. All the results indicated that the acid-liable nanovesicles had a synergistic effect to enhance antitumor efficacy for multidrug-resistant breast cancer treatment.
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2017
·
IF 2.843
Zhigeng Chen,Haohao Huang,Shijing Yan,Zhanping Zheng,Shumei Liu,Yanchao Yuan,Jianqing Zhao,Yi Fu
A new approach to synthesize fluorine-containing graphene oxide (FCGO) was proposed, in which a less toxic reagent was used rather than fluorine gas or anhydrous hydrogen fluoride. The dielectric and mechanical properties of polyimide composites were improved by incorporating a small amount of FCGO. FCGO served as not only nanofiller to lower the dielectric constant of PI films but also inorganic toughening particles to improve the toughness of PI films. The dielectric constant of PI films with 0.6 wt % FCGO was decreased from 3.33 for pure PI to 2.34. In addition, both the tensile strength and Young’s modulus of PI films with 0.6 wt % FCGO were increased to 141 MPa and 4.95 GPa from 118 MPa and 2.81 GPa for pure PI, respectively. In addition, its tensile energy to break was enhanced to 31.6 MJ/m3 from 20.8 MJ/m3.
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危险品化学品经营许可证（带存储）