Polymers
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2023
·Vol. 15
·期 9
·1990
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IF 5
Xinfeng Cheng,Qiyang Li,Xiaomeng Sun,Yuxin Ma,Huanping Xie,Weiguang Kong,Xianchao Du,Zhenghui Zhang,Dongfang Qiu,Yong Jin
Micellar-nanocarrier-based drug delivery systems possessing characteristics such as an excellent circulation stability, inhibited premature release and on-demand site-specific release are urgently needed for enhanced therapeutic efficacy. Therefore, a novel kind of shell-sheddable core-crosslinked polymeric micelles with pH and oxidation dual-triggered on-demand drug release behavior was facilely constructed. The multifunctional micelles were self-assembled from a carefully designed amphiphilic triblock PEGylated polyurethane (PEG-acetal-PUBr-acetal-PEG) employing an acid-labile acetal linker at the hydrophilic–hydrophobic interface and pendant reactive bromo-containing polyurethane (PU) as the hydrophobic block, followed by a post-crosslinking via oxidation-cleavable diselenide linkages. These well-defined micelles exhibited an enhanced structural stability against dilution, achieved through the incorporation of diselenide crosslinkers. As expected, they were found to possess dual pH- and oxidation-responsive dissociation behaviors when exposure to acid pH (~5.0) and 50 mM H2O2conditions, as evidenced using dynamic light-scattering (DLS) and atomic force microscopy (AFM) analyses. An in vitro drug release investigation showed that the drug indomethacin (IND) could be efficiently encapsulated in the micelles, which demonstrated an inhibited premature release compared to the non-crosslinked ones. It is noteworthy that the resulting micelles could efficiently release entrapped drugs at a fast rate in response to either pH or oxidation stimuli. Moreover, the release could be significantly accelerated in the presence of both acid pH and oxidation conditions, relative to a single stimulus, owing to the synergetic degradation of micelles through pH-induced dePEGylation and oxidation-triggered decrosslinking processes. The proposed shell-sheddable core-crosslinked micelles with a pH and oxidation dual-response could be potential candidates as drug carriers for on-demand drug delivery.Keywords:shell-sheddable;core-crosslinking;pH-responsive;oxidation-responsive;drug delivery
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ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Li Xiang,Xin Wang,Yaru Shao,Qiangqiang Jiao,Jiang Cheng,Xiaotong Zheng,Shaobing Zhou,Yuping Chen
As the central cellular player in fibrogenesis, activated hepatic stellate cells (aHSCs) are the major target of antifibrotic nanomedicines. Based on our finding that activated HSCs increase the expression of folate receptor alpha (FRα), we tried to apply folic acid (FA) decoration to generate an active drug-targeting at aHSCs and suppress hepato-fibrogenesis. FA-conjugated poly(ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) were synthesized and self-assembled into the spherical micelles that owned a uniform size distribution averaging at 60 nm, excellent hemo- and cyto-compatibility, and pH-sensitive stability. These FA-modified micelles were preferentially ingested by aHSCs as expected and accumulated more in acutely CCl4 injured mouse livers compared to nondecorated counterparts. Such an aHSC targetability facilitated the loaded medicinal camptothecin (CPT) to achieve a greater therapeutic efficacy and inhibition of MF phenotypic genes in aHSCs. Encouragingly, though free CPT and nontargeting CPT micelles produced negligible curative outcomes, FA-decorated CPT micelles yielded effectively remedial effects in chronically CCl4-induced fibrotic mice, as represented by a significant shrinkage of aHSC population, suppression of fibrogenesis, and recovery of liver structure and function, clearly indicating the success of the folate decoration-supported aHSC-targeted strategy for antifibrotic nanomedicines in fibrosis resolution.
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Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 31
·7478-7489
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IF 7
Lingling Lei,Haibo Wang,Qihan Jia,Yali Tian,Shuang Wang
Due to the rapid development of multi-functional flexible wearable sensors, the development prospects of ionohydrogels with excellent mechanical properties and high sensitivity are necessary. In this work, a novel waterborne polyurethane (WPU) micelle with reactive groups on the surface has been prepared as a crosslinker and then reacted with polyacrylamide (PAM) to obtain a polyacrylamide–polyurethane/ionic liquid (PAM-WPU/IL) ionohydrogel. With the aid of ion–dipole interaction and crosslinks in the composite, the ionohydrogel exhibited ultrastretchability (up to 2927%), good mechanical resilience, and excellent self-adhesion strength (46.01 kPa). Furthermore, the ionohydrogel was used as a strain sensor for monitoring human movement with high strain sensitivity (gauge factor = 35). It is believed that this study provides a new idea for designing a multifunctional ionohydrogel for use in wearable electronics.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Duo Li,Xiaoli Wang,Kaishuo Han,Yaqian Sun,Ting Ren,Guohui Sun,Na Zhang,Lijiao Zhao,Rugang Zhong
Carmustine (BCNU) is a typical chemotherapy used for treatment of cerebroma and other solid tumors, which exerts antitumor effect by inducing DNA damage at O 6 position of guanine. However, the clinical application of BCNU was extremely limited due to the drug resistance mainly mediated by O 6 -alkylguanine-DNA alkyltransferase (AGT) and absence of tumor-targeting ability. To overcome these limitations, we developed a hypoxia-responsive nanomicelle with AGT inhibitory activity, which was successfully loaded with BCNU. In this nano-system, hyaluronic acid (HA) acts as an active tumor-targeting ligand to bind the overexpressing CD44 receptors on the surface of tumor cells. An azo bond selectively breaks in hypoxic tumor microenvironment to release O 6 -benzylguanine (BG) as AGT inhibitor and BCNU as DNA alkylating agent. The obtained HA-AZO-BG NPs with shell core structure had an average particle size of 176.98 ± 11.19 nm and exhibited good stability. Meanwhile, HA-AZO-BG NPs possessed a hypoxia-responsive drug release profile. After immobilizing BCNU into HA-AZO-BG NPs, the obtained HA-AZO-BG/BCNU NPs exhibited obvious hypoxia-selectivity and superior cytotoxicity in T98G, A549, MCF-7 and SMMC-7721 cells with IC 50 at 189.0, 183.2, 90.1 and 100.1 μm, respectively, under hypoxic condition. Near-infrared imaging in HeLa tumor xenograft models showed that HA-AZO-BG/DiR NPs could effectively accumulate in tumor site at 4 h of post-injection, suggesting its good tumor-targetability. In addition, in vivo anti-tumor efficacy and toxicity evaluation indicated that HA-AZO-BG/BCNU NPs was more effective and less harmful compared to the other groups. After treatment, the tumor weight of HA-AZO-BG/BCNU NPs group was 58.46 % and 63.33 % of the control group and BCNU group, respectively. Overall, HA-AZO-BG/BCNU NPs was expected to be a promising candidate for targeted delivery of BCNU and elimination of chemoresistance.
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International Journal of Nanomedicine
·
2023
·
IF 8
Yan Liang,Ping-Yu Wang,Ze-Yun Liu,Hong-Fang Sun,Qin Wang,Guang-Bin Sun,Xia Zhang,You-Jie Li,Shu-Yang Xie
Introduction As the special modality of cell death, immunogenic cell death (ICD) could activate immune response. Phototherapy in combination with chemotherapy (CT) is a particularly efficient tumor ICD inducing method that could overcome the defects of monotherapies.Methods In this study, new dual stimuli-responsive micelles were designed and prepared for imaging-guided mitochondrion-targeted photothermal/photodynamic/CT combination therapy through inducing ICD. A dual-sensitive methoxy-polyethylene glycol-SS-poly(L-γ-glutamylglutamine)-SS-IR780 (mPEG-SS-PGG-SS-IR780) polymer was synthesized by grafting IR780 with biodegradable di-carboxyl PGG as the backbone, and mPEG-SS-PGG-SS-IR780/paclitaxel micelles (mPEG-SS-PGG-SS-IR780/PTXL MCs) were synthesized by encapsulating PTXL in the hydrophobic core.Results In-vivo and -vitro results demonstrated that the three-mode combination micelles inhibited tumor growth and enhanced the therapeutic efficacy of immunotherapy. The dual stimuli-responsive mPEG-SS-PGG-SS-IR780/PTXL MCs were able to facilitate tumor cell endocytosis of nanoparticles. They were also capable of promoting micelles disintegration and accelerating PTXL release. The mPEG-SS-PGG-SS-IR780/PTXL MCs induced mitochondrial dysfunction by directly targeting the mitochondria, considering the thermo- and reactive oxygen species (ROS) sensitivity of the mitochondria. Furthermore, the mPEG-SS-PGG-SS-IR780/PTXL MCs could play the diagnostic and therapeutic roles via imaging capabilities.Conclusion In summary, this study formulated a high-efficiency nanoscale platform with great potential in combined therapy for tumors through ICD.
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Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 44
·9266-9279
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IF 7.571
Zhihao Guo,Junhui Sui,Yumei Li,Qinchuan Wei,Cailing Wei,Linyun Xiu,Ruohua Zhu,Yong Sun,Jianshe Hu,Ji-Liang Li
Nanotechnology-mediated drug delivery systems suffer from insufficient retention in tumor tissues and unreliable drug release at specific target sites. Herein, we developed an epidermal growth factor receptor-targeted multifunctional micellar nanoplatform (GE11-DOX+CEL-M) by encapsulating celecoxib into polymeric micelles based on the conjugate of GE11-poly(ethylene glycol)-b-poly(trimethylene carbonate) with doxorubicin to suppress tumor growth and metastasis. The polymeric micelles maintained stable nanostructures under physiological conditions but quickly disintegrated in a weakly acidic environment, which is conducive to controlled drug release. Importantly, GE11-DOX+CEL-M micelles effectively delivered the drug combination to tumor sites and enhanced tumor cell uptake through GE11-mediated active tumor targeting. Subsequently, GE11-DOX+CEL-M micelles dissociated in response to intracellular slightly acidic microenvironmental stimuli, resulting in rapid release of celecoxib and doxorubicin to synergistically inhibit the proliferation and migration of tumor cells. Systemic administration of GE11-DOX+CEL-M micelles into mice bearing subcutaneous 4T1 tumor models resulted in higher tumor growth suppression and decreased lung metastasis of tumor cells compared with micelles without GE11 decoration or delivering only doxorubicin. Furthermore, the micelles effectively reduced the systemic toxicity of the chemotherapy drugs. This nanotherapeutic system provides a promising strategy for safe and effective cancer therapy.
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EUROPEAN POLYMER JOURNAL
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2022
·
IF 5.546
Hong Wang,Yanwei Zhang,Yaru Liu,Yi Ren,Jianhong Wang,Baolong Niu,Wenfeng Li
Cancer, a cause of high mortality in the world today, is a serious threat to the public health security of various countries. Targeted drug delivery systems with good biocompatibility have become a hot research topic in the field of cancer therapy. In this paper, HA-SS-PLGA copolymer was prepared using cystine (SS) containing disulfide bond as the linker, hyaluronic acid (HA) as the hydrophilic end and poly (lactic- co -glycolic acid) (PLGA) as the hydrophobic end. It will self-assemble in aqueous solution to form amphiphilic micelles with the hydrophilic end outside and the hydrophobic end inside. Among them, SS can react with glutathione in cancer cells by reduction, making the polymer reduction-sensitive. Then, reduction-sensitive Cur-HA-SS-PLGA nanoparticles loaded with Cur were prepared and characterized using curcumin as a model drug. The results showed that HA-SS-PLGA with pH sensitivity and good hemocompatibility could actively target to tumor cell surface overexpression receptors (CD44 receptors) and enter MCF-7 cells through endocytosis, and inhibit the proliferation of cancer cells after drug release. Therefore, the prepared HA-SS-PLGA is expected to be a good drug carrier in the field of cancer therapy.
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Biomaterials Advances
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2022
·
IF 0
Qiying Shen,Quan Hu,Ting Tang,Xiaoying Ying,Gaofeng Shu,Jiawei Shen,Chong Teng,Yongzhong Du
Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease without effective treatment. Tofacitinib (TOF) is a JAK inhibitor that can be used for RA therapy, but it still faces the problems of nonspecific distribution and relatively low therapeutic effect. Herein, ICAM-1-modified TOF-loaded P(AN-co-AAm)-PEG micelles (AI-TM) were developed, which can result in an enhanced RA therapy when combining with microwave hyperthermia (MH). It was found that AI-TM could rapidly release the encapsulated TOF under a thermal condition of >43 °C, which was due to the fact that the polymeric micelles has an upper critical solution temperature (UCST) of 43 °C. AI-TM could specifically distribute into the inflamed joints of RA mice, which is associated with the high affinity between anti-ICAM-1 and overexpressed ICAM-1 receptors. Moreover, the combination of AI-TM and MH could result in a remarkably enhanced anti-rheumatic activity, which was related to the RA-targeted ability of AI-TM, the rapid TOF release under MH, and the combined effect between TOF and MH treatment. Our study definitely provides a novel strategy for effective treatment of RA.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2022
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IF 5.518
Jie Bai,Jie Wang,Yecheng Feng,Yongfang Yao,Xubo Zhao
Polymeric micelles from block copolymers have gained increasing attention in cancer drug delivery. However, the fabrication of polymeric micelles that are stable in biological fluids and unstable at tumor sites remains a principal challenge. To achieve the tunable stability for the polymeric micelles, Zn coordination-induced core-crosslinked polymeric micelles have been proposed and confirmed. Herein, a block copolymer bearing imidazole pendants is synthesized which is capable of self-assembling into polymeric micelles in water. After core-crosslinking, it can be found that the critical micelle concentration (CMC) of the core-crosslinked polymeric micelles is significantly lower than that of non-crosslinked polymeric micelles. Particularly, the drug-loaded core-crosslinked polymeric micelles are fragile and easily affected by the slightly acidic environments, which makes it possible to turn the polymeric micelles back to hydrophilic polymers and therefore disassemble micelles to unload cargoes. The drug-loaded core-crosslinked polymeric micelles display adequate toxicity as a result of their low IC 50 value of 3.713 ± 0.166 μg/mL. Collectively, Zn coordination-induced core-crosslinked polymeric micelles offer a design idea for practicable drug delivery system in cancer therapy.
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POLYMER INTERNATIONAL
·
2021
·Vol. 71
·期 4
·487-494
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IF 2.99
Si Dong,Yue Tang,Pan He,Sheng Ma,Wantong Song,Mingxiao Deng,Zhaohui Tang
Self-assembled polymeric nanoparticle (NP) drug carriers are capable of encapsulated and controlled delivery, facilitating improvements in the therapeutic efficiency of drugs. Here we report a series of poly( l -glutamic acid)- g -methoxy poly(ethylene glycol)/4-phenylbutyl ester (PLG- g -mPEG/PB) copolymers, which were synthesized by esterification of 4-phenylbutanol (PB) and PLG- g -mPEG in different feed ratios. The copolymers obtained form into nano-sized micelles in aqueous solution by a self-assembly process, with lower critical micelle concentration value for higher PB ratio in the copolymers. Variable temperature infrared spectroscopy and circular dichroism were used to prove the breaking of intermolecular hydrogen bonds after PB modification. Podophyllotoxin (PPT), an effective anticancer agent, was incorporated into the inner core of the micelle system by physical entrapment through hydrophobic interaction between the drug and the PB-modified copolymers. Both the drug loading content and the loading efficiency increased with PB content in the PLG- g -mPEG/PB copolymers and reached an ultrahigh value of 28.2 wt% and 94%, respectively. The PPT-encapsulated micelles (PPT-NPs) were stable at pH 7.4 but dissociated and released 80% of loaded PPT in a weak acidic environment (pH 5.0). The in vitro proliferation of non-small-cell lung cancer cells (A549) was significantly inhibited by PPT-NPs in a cytotoxicity assay. These results demonstrate that hydrophobic modification is an efficient route for tuning the self-assembly behaviour and drug encapsulation of PLG- g -mPEG copolymers, and our PLG- g -mPEG/PB will serve as a promising carrier for hydrophobic anticancer drug delivery. © 2021 Society of Industrial Chemistry.
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Soft Matter
·
2023
·Vol. 20
·期 4
·804-812
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IF 3.4
Zhengrong Lin,Hongye Li,Jinpeng Zhang,Xiaomei Pei,Zhao Chen,Zhenggang Cui,Binglei Song
Innovation in surfactant structures is an effective way to prepare new soft materials with novel applications. In this study, we synthesized a double-tailed surfactant containing two quaternary ammonium head groups (Di-C12-N2). The Di-C12-N2 solution behavior was investigated by surface tension, fluorescence, rheology, and cryo-TEM methods. Although Di-C12-N2 contained a large double-tailed hydrophobic group, the solubility of Di-C12-N2 was ∼90 mmol L−1 at 25 °C with a Krafft temperature of ∼1 °C. The increase in Di-C12-N2 concentration in the solutions led to the formation of various aggregates, including spherical micelles, worm-like micelles, multi-layered vesicles, and a rare type of small toroidal micelles. The two quaternary ammonium head groups in Di-C12-N2 led to strong electrostatic interactions between molecules, which was critical for the formation of toroidal micelles. Moreover, with an added NaCl concentration of 40 mmol L−1, the viscosity of the 5 mmol L−1Di-C12-N2 solution increased by ∼1000 times compared to the pure 5 mmol L−1Di-C12-N2 solution, revealing the high sensitivity of the unique head groups to ionic strength. This study enriches the research on the self-assembly principles of surfactants and brings new potential applications for new soft materials.
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JOURNAL OF PHARMACEUTICAL SCIENCES
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2022
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IF 3.784
Meixuan Liu,Sha Liu,Xiaosu Zhu,Yiying Sun,Linyu Su,Hairong Yu,Deshuai Liu,Ying Li,Yuan Du,Rongxia Liu,Kaoxiang Sun
Rosmarinic acid (RA) and tanshinone IIA (TA) which are effective components in Salvia miltiorrhiza show anti-inflammatory potential against atherosclerosis . Based on polysulfated propylene-polyethylene glycol (PPS-PEG), RA was grafted onto this polymer via amide bonds to form a micelle carrier for TA encapsulation: [email protected] A potent inhibitory effect on lipopolysaccharide (LPS) -induced proliferation of endothelial cells with significant intracellular uptake was observed with this system. This could have been the result of release of TA in a reactive oxygen species (ROS) environment and stronger antioxidant effect of RA. The synergistic effect was optimized when the combination was used in a molar ratio of 1:1. Mechanistic studies showed that, compared with PPS-PEG-RA and TA+RA, [email protected] micelles could more effectively regulate the nuclear factor-kappa B (NF-κB) pathway to reduce expression of vascular cell adhesion molecule-1 (VCAM-1), inhibit the inflammatory cascade and reduce endothelial-cell injury. One month after intravenous injection of [email protected] micelles, the plaque area in murine aortic vessels was reduced significantly, and serious toxic side-effects were not observed in vivo , along with excellent biocompatibility . In summary, [email protected] micelles could achieve synergistic treatment of atherosclerosis.
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