NEW JOURNAL OF CHEMISTRY
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2022
·Vol. 46
·期 44
·21235-21244
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IF 3.925
Huan Xu,Mingyue Yang,Yijing Du,Tian Gao,Yi Liu,Liwei Xiong,Na Peng
Nano-drug carriers have been widely used in chemotherapy to improve the efficacy of chemotherapeutic drugs. Polymer nano-carriers have greater potential for the enrichment of chemotherapeutic drugs at the target tumor site and controlled release. Herein, a series of amphiphilic copolymers (ITT) was synthesized via melt polymerization with a ROS-cleavable thioketal cross-linker, imidazole groups, and polyethylene glycol-conjugated triphenylphosphonium (PEG-TPP) segments; the actual proportions of the imidazole groups to the PEG-TPP segments were 5.2 : 1, 2.6 : 1, and 1.8 : 1, respectively. The amphiphilic copolymers could self-assemble into cationic micelles with hydrophobic imidazole groups as the core and hydrophilic PEG-TPP segments as the shell in deionized water. The cationic micelles with an average particle size of 124.6–187.3 nm showed a drug loading content (DLC) of 5.65–6.10%. In vitro release studies revealed the pH/ROS dual-responsiveness of the DOX-loaded ITT micelles, and the release behavior of DOX from the micelles strongly depended on the content of imidazole groups in the ITT micelles. Typically, the release of the encapsulated DOX was 27.2%, 30.0%, and 34.1% from DOX-loaded ITT-1 micelles in PBS (pH 6.5) containing 0, 100, and 500 μM H2O2, respectively. The release of the encapsulated DOX was 20.3%, 27.2%, and 42.5% from DOX-loaded ITT-1 micelles in PBS (pH 7.4), PBS (pH 6.5), and PBS (pH 5.0), respectively. The DOX-loaded micelles effectively inhibited the growth of 4T1 cells through being internalized into the 4T1 cells and releasing DOX into the mitochondria, with a cell viability of less than 65% when the DOX concentration was 2.5 μg mL−1. This work presents a novel mitochondria-targeting and pH/ROS-responsive polymer nanocarrier for potential chemotherapy applications.
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高影响因子
ACS Applied Nano Materials
·
2022
·
IF 6.14
Xinyue Wei,Ziyin Xiang,Weili Xue,Shengfu Chen
Although nanodelivery has made unprecedented progress in enhancing the efficacy of chemotherapeutic drugs, there is still much room for improvement. Zwitterionic nanodrugs have great potential to be a universal platform for nanodelivery because of the exceptional hemocompatibility and ultralow immunogenicity, although they are sensitive to the tumor microenvironment (TME) for tumor cell targeting and internalization. Here, a negatively biased zwitterionic peptide micelle, a mimic of albumin, was developed to improve two vital factors, which are the responsive transition of stability and affinity to tumor cells from circulation to the slightly acidic TME. The incorporation of positively charged hydrophobic phenformin into the camptothecin (CPT)-conjugated micelles (Pep-SSetc-CPT@Phen) can make the micelles more compact to reduce premature drug release in circulation while improving the sensitivity of the micelles to MCF-7-xenografted tumors by tuning their zeta potential in the TME. Thus, Pep-SSetc-CPT@Phen exhibited more tumor-preferred biodistribution and longer blood circulation than nonphenformin-incorporated micelles (Pep-SSetc-CPT), thereby enhancing tumor growth inhibition with lower side effects. Together, these results have provided a promising combinational method to enhance the transition of stability and the sensitivity to the TME for developing biomimetic zwitterionic nanodrugs with high antitumor efficacy.
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2022
·
IF 5.589
Qiangwei Liang,Yang Lan,Yifan Li,Yongjin Cao,Juan Li,Yanhua Liu
Chemotherapeutic agents can trigger the immune response via inducing immunogenic cell death (ICD), but the weak ICD effect induced by chemotherapy alone limits its lasting antitumor immunotherapy effect. A Cro polymerized prodrug carriers (POEG- b -PCro) with immunostimulatory by ICD induction was developed and co-delivered DOX to generate synergistic ICD induction for chemo-immunotherapy on breast cancer. DOX/POEG- b -PCro micelles displayed prolonged circulation in blood, efficient accumulation in tumors, internalization and then co-released DOX&Cro in tumor cells. Moreover, the DOX/POEG- b -PCro micelles synergistically triggered ICD induction by releasing the nuclear high mobility group box 1 (HMGB1) and down-regulation of c-Met level for generating chemo-immune anti-tumor actions. Importantly, the DOX/POEG- b -PCro micelles synergistically enhanced the tumor cytotoxic T lymphocytes infiltration , concomitant decreasing the immunosuppressive regulatory T (Treg) cells, accompanied with the increased cytokines secretion of IFN-γ and TNF-α, consequently displaying an improved anti-tumor activity in 4 T1 breast cancer mice. Overall, POEG- b -PCro prodrug micelles co-delivered DOX could be served as a promising nano drug delivery system for synergistic ICD induction on breast cancer chemo-immunotherapy.
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高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Guofei Li,Limei Zhao
Tumor microenvironment is closely related to the occurrence and development of liver cancer. Tumor-associated macrophages (TAMs) are an important part of tumor microenvironment promoting tumor deterioration and metastasis by inhibiting immune cells. Previous studies showed that PI3Kγ inhibitor could reverse the phenotype of TAMs, relieve immunosuppression and sensitize chemotherapy drugs, suggesting that the combination of PI3Kγ inhibitor and chemotherapeutics is likely to bring new breakthroughs in the treatment of liver cancer. Based on it, this paper builds HES-TG100-115-CDM-PEG micelles with tumor microenvironment responsiveness that simultaneously loaded sorafenib and TG100-115 to synergistically treat liver cancer. Pharmacokinetic study showed that the prepared micelles had longer half-life than that of the free drug solutions, which was favorable for high propensity of extravasation through tumor vascular fenestrations. Under low pH and high α-amylasereductive conditions, micelles could depolymerize quickly due to the sensitivity of bonds and enhance significantly cytotoxic activity against Hep-3B liver cancer cell. Additionally, micelles demonstrated higher levels of antitumor efficiency and better tolerance against nude mouse with Hep-3B cell than the free drug solutions. These findings reveal that HES-TG100-115-CDM-PEG micelles are a promising drug delivery system in clinical comprehensive therapy of liver cancer.
研究领域:
药学
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肿瘤学
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生物医学工程
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高影响因子
MACROMOLECULAR BIOSCIENCE
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2023
·
IF 4.6
Runhai Chen,Yu Xia,Zhifang Ma,Yue Ke,Qiang Shi,Fazly I. Ataullakhanov,Mikhail Panteleev
Excessive amounts of reactive oxygen species (ROS) cause various biological damages and are involved in many diseases, such as cancer, inflammatory and thrombotic complications, and neurodegenerative diseases. Thus, ROS-responsive polymers with inherent ROS scavenging activity and biodegradability are extremely needed for the efficient treatment of ROS-related diseases. Here, this work fabricates the amphiphilic diblock copolymer PEG-b-PBC via ring-opening polymerization (ROP) of phenylboronic acid ester conjugated cyclic carbonate monomer. The copolymer easily forms micelles (BCM) and scavenges ROS rapidly. BCM not only releases the delivered drug but degrades to produce the small molecules p-hydroxybenzyl alcohol (HBA) with anti-inflammatory capability in the presence of H 2 O 2 . BCM can reduce the oxidative stress of human umbilical vein endothelial cells (HUVEC) and the levels of inflammatory factors secreted by macrophages, showing antioxidative and anti-inflammatory activity. Finally, BCM exerts a significant capability to reduce the complications of inflammation and thrombosis in vivo. The biodegradable aliphatic poly(carbonate)s have the potential to be used for drug delivery systems (DDS) for diseases induced by reactive oxygen species.
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高影响因子
Chinese Medicine
·
2023
·Vol. 18
·期 1
·1-14
·
IF 4.9
Guo Zhaopei,Wong Ka Hong,Li Enze,Zhou Xingzhi,Jiang Di,Gao Jiebing,Chen Meiwan
Background The integration of photodynamic therapy with a chemical drug-delivery system has displayed great potential in enhancing anticancer therapy. However, the solubility and non-specific biodistribution of both chemotherapeutic agents and photosensitizers continue to pose challenges that hinder their clinical applications.MethodA polypeptide-based nanoscale drug delivery system was fabricated to address the prementioned issues. An amphiphilic polymer was formed by conjugating the photosensitizer chlorin e6 (Ce6) onto a polypeptide poly-(L-lysine)-b-polyphenylalanine (PKF) for encapsulating the model drug dimeric camptothecin (DCPT), and the nanoparticles (PCD) with high drug loading efficiency were further modified with acid-sensitive polyethylene glycol (PEG) to yield the drug delivery sytem (PPCD).Results The DCPT and Ce6 encapsulation efficiency were analyzed as 99% and 73.5%, respectively. In phosphate-buffered saline (PBS) solution at a pH of 7.4, the PEG shell improved the stability of micelles and shielded their positive charge while in the acidic tumor microenvironment, the pH-sensitive PEG layer was removed to expose the cationic nanoparticles, thus facilitating the cellular uptake of PPCD micelles. Benefiting from the enhanced cellular internalization, the amount of intracellular reactive oxygen species (ROS) treated with PCD and PPCD micelles were obviously increased. Furthermore, the enhanced anti-cancer efficacy prompted by PPCD micelles was validated through cellular and animal study.Conclusion This study presents a promising method to promote the solubility and biodistribution of both chemotherapeutic agent and photosensitizer, thereby facilitating the further application of chemo-photodynamic cancer therapy.Graphical Abstract
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高影响因子
ACS Nano
·
2023
·
IF 17.1
Chao Li,Yuxing Wu,Qinjun Chen,Yifan Luo,Peixin Liu,Zheng Zhou,Zhenhao Zhao,Tongyu Zhang,Boyu Su,Tao Sun,Chen Jiang
Reperfusion injury presents a significant obstacle to neuronal survival following successful recanalization in ischemic stroke, which is characterized by intricate pathophysiological processes comprising numerous interconnected pathways. Oxidative stress-induced neuronal ferroptosis and the overactivation of glial cells play important roles in this phenomenon. In this study, we developed a targeted cross-linked micelle loaded with idebenone to rescue the ischemic penumbra by inhibiting neuronal ferroptosis and glial overactivation. In rat models, the CREKA peptide-modified micelles accumulate in the damaged brain via binding to microthrombi in the ipsilateral microvessels. Upon reactive oxygen species (ROS) stimulation, diselenide bonds within the micelles are transformed to hydrophilic seleninic acids, enabling synchronized ROS consumption and responsive drug release. The released idebenone scavenges ROS, prevents oxidative stress-induced neuronal ferroptosis, attenuates glial overactivation, and suppresses pro-inflammatory factors secretion, thereby modulating the inflammatory microenvironment. Finally, this micelle significantly reinforces neuronal survival, reduces infarct volume, and improves behavioral function compared to the control groups. This pleiotropic therapeutic micelle provides a proof-of-concept of remodeling the lesion microenvironment by inhibiting neuronal ferroptosis and glial overactivation to treat cerebral ischemia-reperfusion injury.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2021
·
IF 4.539
Mengna Zhang,Shujing Zhang,Kun Zhang,Zongyuan Zhu,Yalei Miao,Yudian Qiu,Panke Zhang,Xubo Zhao
Functionality of polymers is crucially fundamental to polymers. However, the application of polymers faces great challenges due to the insufficient function of hydrophobic chain, especially in drug delivery. One novel approach to solve this dilemma involves the use of medicated hydrophobic chains. Herein, the polymer-doxorubicin conjugates are synthesized from hydrophilic copolymer and hydrophobic chain composed of doxorubicin (DOX). DOX, a common hydrophobic anticancer drug , is used to serve as a hydrophobic pendant for inducing self-assembly of polymer-doxorubicin conjugates. The self-assembly of polymer-drug conjugates is employed to encapsulate the unreacted drug for the first time and form drug-loaded polyprodrug micelles that possess a low critical micelle concentration (CMC), which improves the use efficiency of expensive drug. The detachment of DOX moieties from polymer-doxorubicin conjugates caused by amidase facilitates the disintegration of DOX-loaded polyprodrug micelles to trigger the enhanced release of DOX in a slightly acidic medium. It is demonstrated that the DOX-loaded polyprodrug micelles have a higher suppression against cancer cells in in vitro investigations. This work thus proposes a strategy to modify the poor functionality of polymer-based nanostructures , through designing the medicated hydrophobic chains. This strategy facilitates the potential application of polymer-drug conjugates and provides profound insights into the effect of medicated polymer on drug delivery system.
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JOURNAL OF POLYMER RESEARCH
·
2021
·Vol. 28
·期 2
·1-10
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IF 3.097
Liu Wei,Ji Xiangling
The spatial arrangement of functional inorganic nanoparticles within polymer micelles is essential to the nanocomposite performances. Polystyrene (PS) of different lengths (PS 24 , PS 91 and PS 163 ) are grafted onto the surface of fluorescent CdSe/CdS core/shell quantum dots (QDs) through ligand exchange procedure, and their grafting density decreases from 2.80 to 0.54, 0.18 chains/nm 2 with increase of PS ligand length. Under two competing effects, i.e. wettability between QDs and block copolymer PS 120 - b -PEO 318 and the attraction between QDs, the precise location of PS-capped QDs inside the co-assemblies can be regulated by the length of PS ligands. The low grafting density of PS 163 on the QD surface cannot overcome the van der Waals and hydrophobic attraction between QDs and cause the local aggregation of QDs within the co-assemblies. On the contrary, short PS 24 ligands with high grafting density can avoid QD aggregation, but exhibit poor wettability with copolymer, which confines the QDs in the central portion of the core of co-assemblies. PS 91 ligands with medium grafting density have good wettability with block copolymer and facilitate the homogeneous distribution of QDs inside the cores of co-assemblies. Furthermore, the influence of stirring time and water addition rate on the structure of co-assemblies is also investigated.
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2021
·Vol. 28
·期 31
·42694-42705
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IF 4.223
Wu Peng,Liu Yiqing,Fu Yongsheng,Zhou Gaofeng,Deng Jiewen
The solubilization laws of pollutants in micelles and their separation efficiency are very important in the successfully efficient application of micellar enhanced ultrafiltration (MEUF). The solubilization behavior of o -toluidine (OT) and tricyclazole (TC) into sodium dodecyl sulfate (SDS) micelles in MEUF was studied using nonlinear equation sets for concentration analysis, which resolved the issue on the overlap of absorption spectra of multicomponent compounds restricting the application of conventional ultraviolet (UV) spectroscopic method. The solubilization isotherms for both pollutants could be best explained by the Langmuir-Freudlich model ( R 2 >0.99) followed by the modes of Langmuir and Freudlich, inferring the complexity of solubilization mechanism and solubilization advantage of monolayer over multilayer. The calculated thermodynamic parameters ( ΔG 0 , ΔH 0 and ΔS 0 ) indicated that this process was endothermic and spontaneous. The solubilization of OT and TC well followed the pseudo second-order and pseudo first-order kinetics, respectively. The separation and recovery of SDS solubilizing these two pollutants were also investigated through lowering solution temperature to 2 °C followed by centrifugation. The best recovery rate of about 66% for SDS was achieved containing 10 and 5% of each initial amount of OT and TC, respectively, at near-neutral solution pH value. The recovery of SDS could decrease to some extent under alkaline and acidic conditions.
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Drug Delivery and Translational Research
·
2021
·Vol. 12
·期 5
·1080-1095
·
IF 4.617
Su Meiling,Hu Heping,Zhao Xuan,Huang Chengyuan,Yang Bowen,Yin Zongning
This study evaluated the D-mannose modified polyethyleneimine-block-polycaprolactone biomacromolecule copolymer micelles (PCL-PEI-mannose) as a targeted delivery of the glucocorticoid dexamethasone (DXM) to lung inflammation tissues and enhances the vehicle for its anti-inflammatory effects. Dexamethasone was encapsulated in the hydrophobic core of cationic polymer micelles by solvent evaporation. The polymeric micelles exhibited sustained-release within 48 h, good blood compatibility, and colloidal stability in vitro. The cellular uptake of mannose-modified micelles was higher compared with the non-modified micelles. And drug-loaded targeted micelles could inhibit the production of inflammatory factors in activated RAW264.7 cells. The distribution results indicated that drug-loaded targeted micelles highly improved the lung targeting ability, reduced the wet/dry ratio of injured lung tissue, and relieved the lung inflammation, accompanied by the decrease of inflammatory cell infiltration, myeloperoxidase activity, and inflammatory mediator levels in bronchoalveolar lavage fluid. These findings suggested that PCL-PEI-mannose delivery system could facilitate the lung-specific delivery and inhibit the inflammatory response. Collectively, PCL-PEI-mannose polymer micelles could be used as a potential delivery system for the treatment of acute lung injury (ALI). Graphical abstract
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Polymer Chemistry
·
2020
·Vol. 11
·期 48
·7704-7713
·
IF 5.342
Ke Yan,Shujing Zhang,Kun Zhang,Yalei Miao,Yudian Qiu,Panke Zhang,Xu Jia,Xubo Zhao
Designing polymer-based nanostructures through self-assembly has great practical significance in biomedical applications, especially in drug delivery. In general, hydrophobic chains can induce the self-assembly of amphiphilic copolymer to form polymer-based nanostructures in an aqueous phase. However, the application of polymer-based nanostructures has been prevented due to the insufficient functionality of hydrophobic chains. To address these critical issues, the unique tetraphenylethene (TPE) moiety is employed with aggregation-induced emission (AIE) as functional hydrophobic chains to induce copolymer self-assembly and form polymeric micelles that can show strong fluorescence and a low critical micelle concentration (CMC) in aqueous solution. The novel polymeric micelles can efficiently encapsulate doxorubicin (DOX) molecules, and their favorable stability is demonstrated in a physiological medium. More importantly, the disassembly of polymeric micelles is triggered in the presence of esterase, then causing drug release and fluorescence quenching. It is demonstrated that DOX-loaded polymeric micelles have an obvious toxicity against cancer cells. This work confirms that the combination of AIE and self-assembly is an effective strategy for expanding the application of block copolymers and developing new enzyme-responsive polymeric micelles for cancer therapy.
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