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Scientific Reports · 2016 ·Vol. 6 ·期 1 ·1-10 · IF 5.228

CO2-breathing and piercing polymersomes as tunable and reversible nanocarriers

Feng Anchao,Liang Jiamei,Ji Jinzhao,Dou Jinbo,Wang Shanfeng,Yuan Jinying

Despite numerous studies on utilizing polymeric vesicles as nanocapsules, fabrication of tunable molecular pathways on transportable vesicle walls remains challenging. Traditional methods for building penetrated channels on vesicular membrane surface often involve regulating the solvent polarity or photo-cross-linking. Herein, we developed a neat, green approach of stimulation by using CO 2 gas as “molecular drill” to pierce macroporous structures on the membrane of polymersomes. By simply introducing CO 2 /N 2 gases into the aqueous solution of self-assemblies without accumulating any byproducts, we observed two processes of polymeric shape transformation: “gas breathing” and “gas piercing.” Moreover, the pathways in terms of dimension and time were found to be adjustable simply by controlling the CO 2 stimulation level for different functional encapsulated molecules in accumulation, transport, and releasing. CO 2 -breathing and piercing of polymersomes offers a promising functionality to tune nanocapsules for encapsulating and releasing fluorescent dyes and bioactive molecules in living systems and also a unique platform to mimic the structural formation of nucleus pore complex and the breathing process in human beings and animals.

研究领域: 生物化学 · 纳米医学 · 材料科学
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RSC Advances · 2015 ·Vol. 5 ·期 95 ·77986-77995 · IF 3.84

Co-delivery of doxorubicin hydrochloride and verapamil hydrochloride by pH-sensitive polymersomes for the reversal of multidrug resistance

Nuannuan Li,Pei Zhang,Chunzhi Huang,Yunmei Song,Sanjay Garg,Yuxia Luan

In this paper, we synthesized the pH-sensitive and biodegradable amphiphilic polypeptide-based block copolymer methoxy-poly(ethylene glycol)2K-poly(ε-caprolactone)4K-poly(glutamic acid)1K (mPEG2K-PCL4K-PGA1K). mPEG2K-PCL4K-PGA1K had low critical aggregation concentration and could self-assemble into polymersomes in aqueous solution revealed by transmission electron microscopy. Therefore, two hydrophilic drug doxorubicin hydrochloride (DOX) and verapamil hydrochloride (VER) were encapsulated into the mPEG2K-PCL4K-PGA1K polymersomes to form poly(DOX + VER) co-delivery system to reverse the multidrug resistance by inhibiting the expression of P-glycoprotein and improve the anti-cancer effect of DOX. The in vitro cytotoxicity experiments indicated the obviously higher inhibition ratio to MCF-7/ADR resistant cells of poly(DOX + VER) compared with that of free DOX solution and polyDOX. The release rate of the two drugs from poly(DOX + VER) were much slower than that from the free drug solutions, and their release behaviors exhibited high pH-sensitive character. Furthermore, the low hemolysis ratio of mPEG2K-PCL4K-PGA1K confirmed that the copolymer could be applied for intravenous injection safely. Therefore, all these findings indicated that the co-delivery of DOX and VER by mPEG2K-PCL4K-PGA1K polymersomes is very promising for cancer therapy.

研究领域: 药学 · 肿瘤学
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POLYMER · 2022 · IF 4.432

Evaluating the integrity of polymersomes by FRET for optimization of the lyophilization parameters

Yuan Liu,Fei Hu,Shuo Wang,Mengmeng Xu,Qianqian Yu,LinGe Wang

Polymersomes (polymeric vesicles) are non-viral delivery vehicles self-assembled from block copolymers (BCPs), holding promising potential in biomedical applications. Despite the higher chemical stabilities of the BCPs, lyophilization is still required for the long-term preservation of the polymersomes and their encapsulated drugs. However, formulation and processing parameters can affect the efficiency of the lyophilization. In this work, we present an approach to evaluate the integrity of polymersomes based on Fluorescence Resonance Energy Transfer (FRET) for rapid optimization of the lyophilization parameters. Specifically, Coumarin 6 (C6) and Nile red (NR)-encapsulated polymersomes were fabricated separately and mixed together for lyophilization. Upon reconstitution, FRET was detected for polymersomes which lost integrity during the lyophilization or reconstitution. The evaluation was carried out for poly(ethylene glycol)- b -poly(lactic acid) (PEG- b -PLA) polymersomes lyophilized with eight different excipients , and the results showed that the best polymersomes integrity could be achieved with the addition of hydroxypropyl-beta-cyclodextrin (HP-β-CD). We believe the approach described here would greatly facilitate the optimization of the polymersomes lyophilization, accelerating the translation of polymersomes to practical applications.

CAS / MDL: 67-56-1 109-99-9 75-65-0
研究领域: 生物医学工程 · 药物递送系统 · 材料科学
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CHEMISTRY OF MATERIALS · 2024 · IF 7.2

Three-Day Blood Glucose Control via a Glucose Modulator of Glycopolymersome: Sugar versus Sugar

Yufen Xiao,Jiamin Zhang,Tong Wu,Shuai Chen,Zhixiong Huang,Jianzhong Du

Natural modulators, such as insulin, play a significant role in modulating molecule levels. Inspired by the role of natural modulators, herein, we propose a glucose modulator that is composed of a glycopolymersome only to regulate glucose levels. This insulin- and drug-free strategy can smartly take in and snap out glucose according to the surrounding blood glucose levels (BGLs) by reversible sugar substituting. The glycopolymersome is self-assembled from a biodegradable glycopolymer that is composed of sugar and phenylboronic acid derivative, poly(ε-caprolactone)-block-poly[(3-acrylamidophenylboronic acid-stat-N-acryloyl glucosamine] [PCL-b-P(AAPBA-stat-AGA)]. It exhibits excellent long-term hypoglycemic effects toward type 1 diabetic mice for at least 3 days upon one shot without observed side effects, which is the longest effective sugar-regulation time for the insulin and drug-free strategy. Most notably, we explored the effect of the molecular structure of the glycopolymers on the BGL regulating efficacy, where the glucosyl moiety was polymerized with PBA either randomly or separately. Block-statistical glycopolymersomes exhibited lower binding energy to glucose, better glucose responsiveness, and prolonged hypoglycemic effect due to the abundant intramolecular and intermolecular dynamic covalent bonds between AAPBA and AGA. Our finding confirmed the importance of a block-statistical copolymer structure and the key role of sugar in regulating BGLs without involving medication, which may provide guidance and open new avenues for design blood glucose regulating materials.

研究领域: 生物材料学 · 糖尿病研究 · 高分子化学
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY · 2022 · IF 5.141

Preparation of nanogels through photopolymerization at 532 nm with dynamic exposure mode

Chunyue Zhao,Jinfeng Xing

In this study, a new method of photopolymerization with the dynamic exposure was developed to solve the issue of uneven laser-induced polymerization and prepare nanogels with uniform size. Dynamic exposure was used to divide the photopolymerization process into illumination period and dark period. In illumination period, free radicals were generated to induce polymerization. In the dark period, the incompletely cross-linked nanogels and oligomers were redistributed to homogenize the polymerization system. The double bond conversion of the polymerization in the dynamic exposure mode was equal to that in the conventional exposure mode. The simple dynamic exposure mode optimized the process for preparing the nanogels by laser-induced photopolymerization.

CAS / MDL: 26570-48-9
研究领域: 材料科学 · 高分子化学 · 纳米技术
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JOURNAL OF CONTROLLED RELEASE · 2010 · IF 5.949

Polymersomes of asymmetric bilayer membrane formed by phase-guided assembly

Yulong Zhang,Fei Wu,Weien Yuan,Tuo Jin

Encapsulating delicate biomolecules into submicron-sized polymer particulate systems with preserved native conformation and sufficient loading efficiency is of great challenge. To address this issue, we developed a unique polymersome which differs from reported polymersome in that its bilayer membrane was formed of two different amphiphilic diblock copolymers in an “asymmetric” way. By adding two diblock copolymers, poly (ethylene glycol)- block -poly (ε-caprolactone) (PEG-PCL) and dextran- block -poly (ε-caprolactone) (DEX-PCL), into a so-called dextran-in-PEG aqueous two-phase system, DEX-PCL formed the inner leaflet around the dispersed dextran phase and PEG-PCL formed the outer leaflet with the PEG block facing the PEG continuous phase. We name this unique assembly process as “phase-guided assembly”. Polymersomes of asymmetric bilayer membrane possess a series of advantages over “symmetric” polymer bilayer vesicles previously reported. The asymmetric bilayer created a different chemical environment of the interior to which proteins were encapsulated highly efficiently (up to 90%) by thermodynamically favored partition. Probably due to the thermodynamic preference, erythropoietin (EPO) encapsulated in this system showed a well-preserved bioactivity in cell proliferation assay. The core of the polymersomes may be cross-linked to enhance their mechanical strength. Phase-guided assembly system and asymmetric bilayer polymersomes demonstrated in this study may serve the high demands for delivering nucleotide and protein medicines and other biological applications.

研究领域: 材料科学 · 生物医学工程 · 药物递送系统
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BIOMATERIALS · 2016 · IF 8.387

A superparamagnetic polymersome with extremely high T2 relaxivity for MRI and cancer-targeted drug delivery

Qiuming Liu,Liwen Song,Shuai Chen,Jingyi Gao,Peiyu Zhao,Jianzhong Du

Improving the relaxivity of magnetic resonance imaging (MRI) contrast agents is an important challenge for cancer theranostics. Herein we report the design, synthesis, characterization, theoretical analysis and in vivo tests of a superparamagnetic polymersome as a new MRI contrast agent with extremely high T 2 relaxivity (611.6 mM −1 s −1 ). First, a noncytotoxic cancer-targeting polymersome is synthesized based on a biodegradable diblock copolymer , folic acid-poly( l -glutamic acid)- block -poly( ε -caprolactone) [FA-PGA- b -PCL]. Then, ultra-small superparamagnetic iron oxide nanoparticles (SPIONs) are in situ generated in the hydrophilic PGA coronas of polymersomes to afford magnetic polymersomes. The in vivo MRI assay revealed prominent negative contrast enhancement of magnetic polymersomes at a very low Fe dose of 0.011 mmol/kg. Moreover, this cancer-targeting magnetic polymersome can effectively encapsulate and deliver anticancer drug to inhibit the tumor growth, demonstrating promising theranostic applications in biomedicine .

研究领域: 生物医学工程 · 纳米医学 · 分子影像学
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JOURNAL OF CONTROLLED RELEASE · 2021 · IF 9.776

Tumor-dilated polymersome nanofactories for enhanced enzyme prodrug chemo-immunotherapy

Abd Al-Wali Mohammed M. Japir,Wendong Ke,Junjie Li,Jean Felix Mukerabigwi,Alhadi Ibrahim,Yuheng Wang,Xiang Li,Qinghao Zhou,Fathelrahman Mohammed,Zhishen Ge

Combination chemo-immunotherapy of cancers has attracted great attention due to its significant synergistic antitumor effect. The response rates and therapeutic efficacy of immunotherapy can be enhanced significantly after proper combination with chemotherapy. However, chemo-immunotherapy is frequently limited by severe immune-related adverse events and systemic side toxicity. In this report, efficient nanofactory-directed enzyme prodrug chemo-immunotherapy is demonstrated based on enzyme-loaded tumor-dilatable polymersomes with optimized membrane cross-linking density. Upon intravenous injection of the nanofactories, they can passively accumulate at the tumor site. The tumor pH-responsive nanofactories can swell from ~100  nm to ~200 nm under the trigger of tumor acidity, leading to prolonged retention of up to one week inside tumor tissues. Simultaneously, the membrane permeability of the nanofactories has improved significantly, which allows hydrophilic small molecules to pass across the membranes while keeping the enzymes in the inner cavities. Subsequently, the non-toxic prodrug mixtures of chemo-immunotherapy are administrated three times within 6 days, which are in situ activated by the nanofactories selectively at tumor sites. Activated chemotherapeutic drugs kill cancer cells and generate tumor-associated antigens to promote the maturation of dendritic cells. Activated indoleamine 2, 3-dioxygenase 1 inhibitors reverse the immunosuppressive tumor microenvironment . Finally, primary tumors can be effectively suppressed while causing minimal systemic toxicity. The distant tumors that are established after treatment can also be inhibited completely via activation of antitumor immunity in mice. Thus, the tumor-dilatable polymersome nanofactories with long-term intratumoral retention offer a promising paradigm for enhanced enzyme prodrug chemo-immunotherapy.

CAS / MDL: 3068-32-4
研究领域: 癌症治疗 · 纳米医学 · 免疫学 · 药学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2017 · IF 3.887

Amino-functionalized nano-vesicles for enhanced anticancer efficacy and reduced myelotoxicity of carboplatin

Xiumei Zhu,Yan Peng,Liyan Qiu

Carboplatin is one of the few platinum-based antitumor drugs used worldwide. Unfortunately, systemic carboplatin therapy is limited by its dose-related myelosuppression. In this study, a viable way to reduce the serious myelotoxicity of carboplatin while improving its therapeutic efficacy using amino-functionalized polyphosphazene vesicles is reported. First, three polyphosphazenes with different amino content were synthesized by amidating hydrophobic side groups; these polyphosphazenes could self-assemble into polymersomes with similar particle size and morphology. Based on FTIR analysis, hydrogen bonding interactions between the polymeric carriers and carboplatin were validated and shown to predominantly contribute to the significant improvement of drug loading in polymersomes. Therefore, it turned out that the amino level of polymers played a substantial role in carboplatin encapsulation. Then, PEAP-2-C polymersomes were optimized for further experimental verification to achieve depressed carboplatin-induced myelotoxicity as well as promote curative effects against CT-26 colon adenocarcinoma. These results in vitro and in vivo proved that amino-functionalized polyphosphazene vesicles have great potential for carboplatin delivery in the application of cancer therapy.

CAS / MDL: 4097-89-6
研究领域: 药学 · 纳米技术 · 癌症治疗
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Nanoscale · 2013 ·Vol. 6 ·期 6 ·3250-3258 · IF 6.233

The proton permeability of self-assembled polymersomes and their neuroprotection by enhancing a neuroprotective peptide across the blood–brain barrier after modification with lactoferrin

Yuan Yu,Xinguo Jiang,Shuyu Gong,Liang Feng,Yanqiang Zhong,Zhiqing Pang

Biotherapeutics such as peptides possess strong potential for the treatment of intractable neurological disorders. However, because of their low stability and the impermeability of the blood–brain barrier (BBB), biotherapeutics are difficult to transport into brain parenchyma via intravenous injection. Herein, we present a novel poly(ethylene glycol)–poly(D,L-lactic-co-glycolic acid) polymersome-based nanomedicine with self-assembled bilayers, which was functionalized with lactoferrin (Lf-POS) to facilitate the transport of a neuroprotective peptide into the brain. The apparent diffusion coefficient (D*) of H+ through the polymersome membrane was 5.659 × 10−26 cm2 s−1, while that of liposomes was 1.017 × 10−24 cm2 s−1. The stability of the polymersome membrane was much higher than that of liposomes. The uptake of polymersomes by mouse brain capillary endothelial cells proved that the optimal density of lactoferrin was 101 molecules per polymersome. Fluorescence imaging indicated that Lf101-POS was effectively transferred into the brain. In pharmacokinetics, compared with transferrin-modified polymersomes and cationic bovine serum albumin-modified polymersomes, Lf-POS obtained the greatest BBB permeability surface area and percentage of injected dose per gram (%ID per g). Furthermore, Lf-POS holding S14G-humanin protected against learning and memory impairment induced by amyloid-β25–35 in rats. Western blotting revealed that the nanomedicine provided neuroprotection against over-expression of apoptotic proteins exhibiting neurofibrillary tangle pathology in neurons. The results indicated that polymersomes can be exploited as a promising non-invasive nanomedicine capable of mediating peptide therapeutic delivery and controlling the release of drugs to the central nervous system.

CAS / MDL: 123-91-1
研究领域: 纳米医学 · 神经科学 · 药学 · 生物技术
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PHARMACEUTICAL RESEARCH · 2016 ·Vol. 34 ·期 3 ·610-618 · IF 3.26

Biodegradable Polymersomes as Nanocarriers for Doxorubicin Hydrochloride: Enhanced Cytotoxicity in MCF-7/ADR Cells and Prolonged Blood Circulation

Chao Yanhui,Liang Yuheng,Fang Guihua,He Haibing,Yao Qing,Xu Hang,Chen Yinrong,Tang Xing

Purpose DOX is one of the most potent anticancer drugs. But its short half-life and the occurrence of multi-drug resistance (MDR) markedly limit its clinical application. To solve these problems, we develop DOX loaded polymersomes (DOX polymersomes). Methods An methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone) (mPEG-b-PCL) copolymer was synthesized and used to prepare DOX polymersomes. The pharmaceutical properties of DOX polymersomes were characterized. The in vitro release profile of DOX from polymersomes was investigated. The in vitro cytotoxicity and cell uptake studies were performed on MCF-7 and MCF-7/ADR cells. The in vivo pharmacokinetic profiles were investigated on Sprague–Dawley rats. Results DOX polymersomes had a nano-scale particle size of about 60 nm with a hydrophobic membrane about 10 nm in thickness. Release of DOX from the polymersomes took place in a sustained manner. Cell experiments showed DOX polymersomes enhanced the cytotoxicity and the intracellular accumulation of DOX in MCF-7/ADR cells, compared with free DOX. In vivo pharmacokinetic study showed the DOX polymersomes increased the bioavailability and prolonged the circulation time in rats. Conclusions The entrapment of DOX in biodegradable polymersomes could enhance cytotoxicity in MCF-7/ADR cells and improve its in vivo pharmacokinetic profile.

研究领域: 药剂学 · 肿瘤学 · 纳米技术 · 药物递送系统
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GIANT · 2022 · IF 0

Polymersomes as virus-surrogate particles for evaluating the performance of air filter materials

Shuo Wang,Yuan Liu,Mengmeng Xu,Fei Hu,Qianqian Yu,Linge Wang

The development of antivirus air filter materials has attracted considerable interests due to the pandemic of coronavirus disease 2019 (COVID-19). Filtration efficiency (FE) of these materials against virus is critical in the assessment of their use in disease prevention. Due to the high cost and biosafety laboratory required for conducting research using actual virus samples, surrogates for virus are commonly used in the filtration test. Here, we explore the employment of polymersomes (polymeric vesicles) as a new type of surrogate. The polymersomes are hollow shell nanoparticles with amphiphilic bilayer membranes, which can be fabricated in nanosized, and possess similar size and structural features to virus. The performance of commercial KN95 mask and surgical mask with micro-sized fibers, and electrospun polyvinylidene fluoride (PVDF) and polyacrylonitrile (PAN) nanofibers were chosen to be evaluated. The filtration tests against fluorescent-labeled virus-surrogate particles (VSPs), i.e. polymersomes, allowed the determination of the FE of the multilayered filter materials in a layer-specific manner. The results suggested the importance of hydrophobicity in designing the nanofibrous filter materials. The employment of VSPs in filtration performance evaluation allows a cost-effective way to estimate the FE against virus, providing guidance on future development of air filter materials.

研究领域: 材料科学 · 纳米技术 · 病毒学 · 环境工程 · 生物医学工程
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