Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 47
·11319-11334
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IF 7
Pengpeng Jia,Yu Zou,Jiang Jiang
Constructing antibacterial and antioxidant hydrogels is critical for treating infected full-thickness skin wounds. Herein, we report a co-encapsulation strategy to load CuS nanoparticles and hydrophobic antioxidant curcumin (cur) in aldehyde-terminated F127 micelles, which are then cross-linked with carboxymethyl chitosan through a Schiff base reaction to form a functional composite hydrogel (CF–CuS–cur). Apart from its suitable swelling and degradation behavior, good biocompatibility, and injectability for treating irregular wounds, the CF–CuS–cur hydrogel displayed excellent photothermal antibacterial ability under 1064 nm NIR laser irradiation, and antioxidant activity to protect cells from excessive oxidative stress. Using a full-thickness infected wound model, we demonstrated that the CF–CuS–cur hydrogel accelerated the wound healing process by effective sterilization and decreased inflammation, under synergistic action from CuS, curcumin and NIR irradiation. Histological and immunohistochemistry analysis further revealed the promoted skin attachments and regeneration, collagen deposition, neovascularization, and early transition to anti-inflammatory M2 macrophages, when the wounds were treated with the CF–CuS–cur hydrogel. This work demonstrates a facile strategy to construct functional hydrogels with NIR-enhanced antibacterial and antioxidant properties, which can be potentially applied as wound dressings for treating chronic wounds.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
·
IF 5.8
Kehong Dong,Yuxuan Sun,Xintao Gao,Jing Wang,Xiaochen Wu,Chuanlong Guo
Excessive acetaminophen (APAP) is the main cause of drug-induced acute liver failure, and the pathogenesis has not been elucidated and there is a lack of effective drugs. Hesperidin (Hes), a rich flavanone in citrus peel with excellent biological activities, is a potential agent for treatment liver injury. Due to poor water solubility of Hes, this study prepared mixed micelles using polyvinyl pyrrolidone (PVP K17) and poloxamer 188, and encapsulated Hes (Hes-MMs). The results showed that Hes-MMs exhibited a uniform spherical shape with a particle size of 66.80 ± 0.83 nm, and Hes-MMs significantly improved the dispersibility, antioxidant activity , and cellular uptake of Hes. In vitro results showed that Hes-MMs protected the proliferation inhibition of HepG2 cells induced by APAP, inhibited the production of reactive oxygen species (ROS) and the damage of mitochondrial membrane potential (MMP) induced by APAP. Furthermore, Hes-MMs exerted liver protective effects by inhibiting APAP induced mtDNA release and activating the cGAS-STING pathway. In vivo results demonstrated that Hes-MMs showed protective and therapeutic effects on APAP induced liver injury, and their mechanisms were related to the mtDNA-cGAS-STING signaling pathway . In summary, our study demonstrated that the mtDNA-cGAS-STING pathway was involved in APAP induced acute liver injury, and Hes-MMs might be a potential therapeutic agent for treating APAP induced acute liver injury.
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EUROPEAN POLYMER JOURNAL
·
2023
·
IF 6
Pu Li,Qiang Liu,Zhenni Xiang,Jian Wang,Wan-Xia Wu,Wen-Jing Yi
The reactive oxygen species (ROS) responsive amphiphilic poly(ethylene glycol)- b -poly(thioketal) (mPEG- b -PTK) copolymer was synthesized by enzyme-catalyzed polymerization for the first time. Core crosslinked (CCL) micelles were prepared via thiol-ene click reaction between the double bond of the side chain of mPEG- b -PTK and the thiol group of pentaerythritol tetrakis (3-mercaptopropionate) as a crosslinker under UV light. The success of crosslinking was verified by NMR and IR. CCL micelles showed better stability in stability against dilution and storage stability experiments compared with the uncrosslinked (UCL) micelles. The ROS-responsiveness of CCL micelles was characterized by DLS, TEM, NMR, AFM and SEM. In vitro release studies, CCL micelles encapsulating doxorubicin (DOX) showed a faster release rate of nearly 100% within 32 h in PBS containing 5 mM H 2 O 2 compared to the control without H 2 O 2 . Cytotoxicity test demonstrated good biocompatibility of CCL micelles and low toxicity with cell viability above 82% and 86% in HeLa cells and HUVEC cells, respectively. And CCL DOX-loaded micelles exhibited great anticancer activity with IC 50 value about 4.8 mg/L for Hela cells. Finally, flow cytometry and confocal laser scanning microscope (CLSM) showed that DOX-loaded micelles had excellent internalization efficiency in HeLa cells. The obtained ROS-responsive CCL micelles held promise for anticancer drug delivery.
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ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Jiamin Chen,Xingxing Liu,Shujing Zhao,Hongyican Chen,Tao Lu,Jinfeng Wang,Jiahui Han,Wangran Wu,Xian Shen,Chao Li
Due to the intrinsic weak immunogenicity of tumor cells and the quantitatively and functionally different populations of immune cells, immunosuppression has become the major obstacle for cancer immunotherapy. In this study, the biocompatible alginate was chemically modified with the carboxyethyl linker to facilitate the esterification reaction of the resultant carboxymethylated alginate (CMA) and resiquimod (R848), the agonist of Toll-like receptor 7/8 (TLR7/8a). In aqueous solution, the hydrophilic CMA and the hydrophobic R848 formed stable nanomicelles (CMA-R848) by self-assembling. After combined administration of CMA-R848 and cisplatin (Cis) in a gastric cancer (GC) model, the long-circulating CMA-R848 micelle reached the mild acidic tumor microenvironment (TME); the ester bonds were quickly cleaved by the ubiquitous esterase and released the single molecule of R848. In vitro and in vivo results demonstrated that the released R848 efficiently promoted co-stimulatory molecules’ expression of dendritic cells (DCs), enhanced the antigen uptake and cross-presentation, and primed the cytotoxic T lymphocytes’ (CTLs) infiltration and killing effects, thereby reprogramming the “cold tumor” into the “hot tumor”. In addition, the ex vivo tumor sections revealed that the released R848 effectively repolarized the M2-like tumor-associated macrophages (TAMs) into M1-like macrophages, exerted synergistic antitumor activity, reduced the tumor burden, and prolonged the overall survival duration of the GC animal model. Our study provided a targeting therapeutic strategy overcoming the limitations of R848 in vivo, and enhanced the efficacy of GC chemotherapy and immunotherapy by TME modulation.
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JOURNAL OF APPLIED POLYMER SCIENCE
·
2023
·Vol. 140
·期 44
·e54614
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IF 3
Yingxue Xu,Na Liang,Jia Fu,Zhe Zong,Xueling Long,Shaoping Sun
In this study, a polymer with tumor targeting function and dual redox/pH sensitivity is designed and synthesized by integrating chitosan (CS), Poloxamer 407 (P407), cholesterol (CHO), folic acid (FA), and disulfide bonds into one molecule (P407-CS(FA)-SS-CHO). The polymer can self-assemble in water to form micelles and solubilize paclitaxel (PTX). The mean particle size of PTX-loaded P407-CS(FA)-SS-CHO micelles is 133 nm. In vitro drug release study demonstrates the acid and glutathione (GSH) triggered PTX release behavior of the micelles. In vitro and in vivo experiments demonstrate the excellent tumor growth inhibition efficacy and low systemic toxicity of the PTX-loaded micelles. The P407-CS(FA)-SS-CHO micelles will be potential intelligent drug carriers for PTX delivery.
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INDUSTRIAL CROPS AND PRODUCTS
·
2023
·
IF 5.9
Pengfei Shan,Ming Zhang,Xiaoyue Lian,Weilin Lu,Xiangping Yin,Haiwei Liu,Yingwen Lu,Qi Yuxi,Jiabin Jiang,Zhihui Li,Zhongyu Li
The low utilization efficacy of conventional herbicide formulations greatly harms the environment and human health. Inspired by the fact that many drug delivery systems are designed to achieve targeted release triggered by the microenvironment of tumor tissues in cancer therapy, a tartaric acid-derived polyester with hydrophilic acid-degradable side chains was designed and synthesized for site-specific herbicide delivery by utilizing the acidic microenvironment in the rhizosphere . The amphiphilic polymer can spontaneously form polymeric micelles in the aqueous solution to load diuron. The diuron-loaded polymeric micelles can release diuron under acidic conditions, and the release rate increase with the reduction of pH value. The herbicidal effect of the diuron-loaded polymeric micelles is investigated using barnyard grass as the research object. The results reveal that the diuron-loaded polymeric micelles are able to kill barnyard grass effectively. Finally, the toxicity studies suggest that the polymer can mitigate toxicity to the non-target organisms. In view of its superior herbicidal activity, excellent biodegradability and biocompatibility, this site-specific herbicides release system has broad potential in agricultural applications.
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FUEL
·
2023
·
IF 7.4
Mingwei Gao,Mingshan Zhang,Peng Liu,Caili Dai,Qing You,Qiang Xue,Mingwei Zhao,Zhehui Jin
CO 2 enhanced oil recovery (CO 2 -EOR) is one of the CO 2 utilization methods which can also geo-sequestrate greenhouse gases. Due to the weak adsorption on rock surface and excellent viscoelasticity performance, CO 2 -responsive zwitterionic wormlike micelles (WLMs) has been recognized as a promising method to control CO 2 channeling. A novel CO 2 responsive zwitterionic WLMs was developed by blending N -octadecyl- N , N -dimethyl-3-ammonio-2-hydroxy-1-propane-sulfonate (OHSB), N , N , 2 , 2 -tetramethyl-1,3-propanediamine (TADPA) and sodium salicylate (NaSal). The responsive behaviors induced by varying agents (CO 2 and HCl) are systematically studied by rheology tests and cryo-TEM measurements. The molecular structures of products are confirmed by 1 H and 13 C NMR. Moreover, the responsive mechanism is discussed in detail. The OHSB/NaSal/TADPA system shows morphological transformations between spherical micelles (a good flowing capacity) and WLMs (conducive to plugging) before and after purging CO 2 . The viscoelasticity and molecular structure of the system with CO 2 bubbling is different from that with HCl titration, because TADPA molecules can react with CO 2 to form a novel zwitterionic product: NH + (CH 3 ) 2 -CH 2 -C(CH 3 ) 2 -CH 2 -NHCO 2 − (TAH + DPACO 2 − , 78.95 %–83.52 %). This work provides a new strategy for the design of CO 2 -responsive zwitterionic WLMs and their applications in CO 2 utilization schemes, including clean fracturing, mobility control, and CO 2 foam flooding, etc.
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Drug Delivery and Translational Research
·
2023
·
IF 5.4
Xiao Chuyao,Li Genyun,Li Xiaoyue,Wang Dan,Wu Ya,Sun Minghui,Huang Jiangeng,Si Luqin
Ulcerative colitis (UC) is an idiopathic, chronic, relapsing disease. In most cases, only the distal colon is affected, and the colonic stasis or fast colonic transit through the inflamed colon usually results in reduced exposure of the distal inflamed colon. Although the immunosuppressant cyclosporine A (CsA) has been used in patients with severe colitis who do not respond to corticosteroids, the clinical application of CsA remains limited due to the systemic toxicities and insufficient accumulation at the site of action for the intravenous and oral routes. In this study, we loaded CsA into the amphipathic poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) micelles and then embedded them in hydrogels consisting of chitosan, poloxamer 188, and poloxamer 407 to construct a thermosensitive and mucoadhesive hydrogel drug delivery system (PLCP). The PLCP presented a high drug-loading capacity and showed a stable and rapid gelation rate after rectal administration into the body. Compared to CsA-loaded micelles and Sandimmun (Neoral ® ), the developed thermosensitive gel exhibited prolonged retention on the inflamed colon, as seen from in vitro adhesion and in vivo distribution experiments. It also fast mitigated colitis symptoms in TNBS-treated mice by regulating the expression levels of proinflammatory cytokines (TNF-α, IL-1β, COX-2, and iNOS2), anti-inflammatory cytokines (IL-10, Nrf2, NQO1, and HO-1), and other relevant biochemical factors. Our results suggested that CsA-loaded micelle thermal hydrogel system could be a promising strategy by enhancing the retention in the diseased colon and promoting the relief and recovery of UC. Graphical Abstract
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International Journal of Nanomedicine
·
2023
·
IF 8
Yupeng Liu,Suhuan Dai,Lijuan Wen,Yun Zhu,Yanan Tan,Guoxi Qiu,Tingting Meng,Fangying Yu,Hong Yuan,Fuqiang Hu
Background Phototherapy is a potential new candidate for glioblastoma (GBM) treatment. However inadequate phototherapy due to stability of the photosensitizer and low target specificity induces the proliferation of neovascular endothelial cells for angiogenesis and causes poor prognosis.Methods In this study, we constructed c(RGDfk)-modified glycolipid-like micelles (cRGD-CSOSA) encapsulating indocyanine green (ICG) for dual-targeting neovascular endothelial cells and tumor cells, and cRGD-CSOSA/ICG mediated dual effect of PDT/PTT with NIR irradiation.Results In vitro, cRGD-CSOSA/ICG inhibited cell proliferation and blocked angiogenesis with NIR irradiation. In vivo, cRGD-CSOSA/ICG exhibited increased accumulation in neovascular endothelial cells and tumor cells. Compared with that of CSOSA, the accumulation of cRGD-CSOSA in tumor tissue was further improved after dual-targeted phototherapy pretreatment. With NIR irradiation, the tumor-inhibition rate of cRGD-CSOSA/ICG was 80.00%, significantly higher than that of ICG (9.08%) and CSOSA/ICG (42.42%). Histological evaluation showed that the tumor vessels were reduced and that the apoptosis of tumor cells increased in the cRGD-CSOSA/ICG group with NIR irradiation.Conclusion The cRGD-CSOSA/ICG nanoparticle-mediated dual-targeting phototherapy could enhance drug delivery to neovascular endothelial cells and tumor cells for anti-angiogenesis and improve the phototherapy effect of glioblastoma, providing a new strategy for glioblastoma treatment.
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ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 29
·期 13
·1806620
·
IF 15.621
Yujie Zhang,Xi Zhu,Xinli Chen,Qinjun Chen,Wenxi Zhou,Qin Guo,Yifei Lu,Chao Li,Yu Zhang,Donghui Liang,Tao Sun,Xunbin Wei,Chen Jiang
The frequent relapse and metastasis characteristics of triple negative breast cancer (TNBC) make it a fraught issue with very poor prognosis in clinic. An effective treatment for TNBC should prevent and even eliminate metastasis as well as suppress primary lesion expansion. Recent progress reveals that platelets can be recruited and activated by tumor cells through intercellular adhesion molecules (ICAM), and help aggressive circulating tumor cells (CTCs) form metastasis. Therefore, activated platelets are considered with possession of tumor-homing, CTC-capturing, and metastasis-targeting abilities. In this work, a P-selectin (expressed on activated platelet surface) targeting peptide (PSN) is modified on a redox-responsive paclitaxel-loaded micelle (PSN-PEG-SS-PTX 4 micelle) to utilize activated platelets as a “bridge” for interaction with cancer cells. The PSN-modified micelle can easily adhere to the surface of activated platelets and subsequently capture CTCs in blood circulation. Compared to Taxol and PEG-SS-PTX 4 micelle, PSN-PEG-SS-PTX 4 micelle also exhibits enhanced primary TNBC/metastasis targeting and penetrating effect through binding with tumor infiltrating platelets and thus significantly improves treatment outcome. More importantly, PSN-PEG-SS-PTX 4 micelle potently suppressed lung metastasis of TNBC and reduced incidence of distant liver metastasis. The activated platelet-targeting redox-responsive micelle system provides a promising prospect for the omnidirectional treatment of metastatic cancer.
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Advanced Healthcare Materials
·
2018
·Vol. 7
·期 24
·1801094
·
IF 5.609
Guoqing Wei,Yi Wang,Xuehui Huang,Guang Yang,Jingya Zhao,Shaobing Zhou
The accumulation of nanoparticles in tumors by the enhanced permeability and retention (EPR) effect is effective and well known. However, how to maximize accumulation is still a bottleneck in the development of nanomedicine. Herein, a tumor vascular-targeted hybrid polymeric micelle, which has a great capacity to selectively augment the EPR effect of nanoparticles by dilating tumor blood vessels via the activity of nitric oxide (NO), is presented. Under neutral conditions, the micelle is stable, with a long blood circulation half-life due to the carboxylated poly(ethylene glycol) (PEG) layer; in mildly acidic tumor tissues, the micelle can selectively target the tumor blood vessels by the exposed cyclic Arg-Gly-Asp peptide (cRGD) peptides, which is realized with a pH-dependent hydrolysis of the monomethoxy PEG layer. Simultaneously, exposed copper ions catalyze the decomposition of endogenous NO donors, which generates NO in situ, leading to vasodilation and increased tumor vascular permeability. As a result, the accumulation of nanoparticles is significantly enhanced, and a high accumulation of doxorubicin in tumors is achieved at 48 h after injection. This high dose of therapeutic agent produces a large inhibition of tumor growth (94%) in cancer treatment, and shows no general toxicity, with 100% of the mice surviving the treatment regimen.
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Polymers
·
2019
·Vol. 11
·期 3
·511
·
IF 3.164
Jingjie Feng,Weiqiu Wen,Yong-Guang Jia,Sa Liu,Jianwei Guo
One of the most famous anticancer drugs, paclitaxel (PTX), has often been used in drug controlled-release studies. The polymers derived from bio-compound bile acids and degradable poly(ε-caprolactone) (PCL) form a reservoir and have been used as a drug delivery system with great advantages. Herein, we grafted poly(N,N-diethylaminoethyl methacrylate) and poly(poly(ethylene glycol) methyl ether methacrylate) into the bile acid-derived three-armed macroinitiator CA-(PCL)3, resulting in the amphiphilic block copolymers CA-(PCL-b-PDEAEMA-b-PPEGMA)3. These pH-responsive three-armed block copolymers self-assembled into micelles in aqueous solution and PTX was encapsulated into the micellar core to form PTX-loaded micelles with a drug loading of 29.92 wt %. The micelles were stable in PBS at pH 7.4 and showed a pH-triggered release behavior of PTX under acidic environments, in which 55% of PTX was released at pH 5.0 in 80 h. These cholic acid-based functionalized three-armed block polymers present good biocompatibility, showing great potential for drug controlled-release.Keywords:cholic acid;pH-sensitive;PTX;drug delivery
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