Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 3
·440-448
·
IF 0
Weifeng Lin,Guanglong Ma,Fangqin Ji,Juan Zhang,Longgang Wang,Haotian Sun,Shengfu Chen
Polyethylene glycol (PEG) is considered to be the most effective material to prolong the circulation time of nanoparticles by reducing non-specific protein adsorption in blood. However, it is recognized that PEG decomposes in most physiological solutions, and an anti-PEG antibody has been detected in some normal blood donors as a response to injection with PEGylated polymer particles. Zwitterionic polymers are potential alternatives to PEG for biomedical applications because of their super resistance to non-specific protein adsorption. Thus, finding one polymer with a long circulation time and resistance to the immune response is of significant importance. Here, we prepared four star carboxybetaine polymers of different molecular weights via atom transfer radical polymerization (ATRP) from a β-cyclodextrin (β-CD) initiator for investigating the biocompatibility of carboxybetaine polymer, a typical zwitterionic polymer. The circulation half-life of the largest star polymer (123 kDa) in mice was prolonged to 40 h in vivo, with no appreciable damage or inflammation observed in the major organ tissues. Furthermore, the circulation time of repeat injections showed similar results to the first injection, with no obvious increase in the amount of antibody in blood. The internalization of the star carboxybetaine polymers by macrophage cells was a relatively slow process. The high cell viability in the presence of star carboxybetaine polymers up to 2 mg mL−1 was maintained. The hemolytic activity of the star carboxybetaine polymers at 5 mg mL−1 was almost undetectable. In vitro results prove a key prediction of excellent biocompatibility in vivo. All the results suggest that the carboxybetaine polymer, perhaps even most of the zwitterionic ones, might be a good alternative to PEG in the development of a drug delivery system.
研究领域:
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
JOURNAL OF MEDICINAL CHEMISTRY
·
2021
·
IF 7.446
Yang Li,Jianfeng Gao,Shuping Wang,Mingxia Du,Xiaowen Hou,Tian Tian,Xue Qiao,Zhiquan Tian,Peter J. Stang,Shijun Li,Xuechuan Hong,Yuling Xiao
Complete excision of the last remaining 1–2% of tumor tissue without collateral damage remains particularly challenging. Herein, we report thiophenthiadiazole (TTD)-derived fluorophores L6-PEGnk (n = 1, 2, 5) as new-generation NIR-II (1000–1700 nm) probes with exceptional nonfouling performance and significantly high fluorescence quantum yields in water. L6-PEG2k can self-assemble into vesicular micelles and exhibited minimal immunogenicity, low binding affinities, ultralong blood circulation (t1/2 = 59.5 h), and a supercontrast ratio in vivo. Most importantly, L6-PEG2k achieved excellent in vivo CT-26 and U87MG tumor targeting and accumulation (>20 d) through intraperitoneal or intravenous injection. A subcutaneous U87MG tumor and orthotopic brain glioma were successfully resected under NIR-II FIGS in our animal model via intraperitoneal injection in an extended time window (48–144 h). This study highlights the potential of using L6-PEG2K as self-assembling molecular probes with long-circulation persistence for routine preoperative tumor assessment and precise intraoperative image-guided resection.
研究领域:
生物医学工程
·
分子影像学
·
癌症研究
✓ 已验证
DOI
高影响因子
Science China-Chemistry
·
2014
·Vol. 57
·期 4
·633-644
·
IF 1.516
Cao Ming,Liu XiangRui,Tang JianBin,Sui MeiHua,Shen YouQing
The stability and size of polymeric nanoparticles are two of the most important parameters determining their pharmacokinetics and tumor/drug accumulation efficiency in cancer-drug delivery. Herein, we report a facile one-pot synthesis of crosslinked nanoparticles (CNPs) with tunable sizes and polyethylene glycol (PEG) shells via click reactions. Simply by adjusting the contents of the macromonomer (PEG monoacrylate) in its reaction with ethylene diacrylate and a crosslinker containing hexa-thiols groups, the sizes of the resulting PEGylated crosslinked nanoparticles could be easily tuned from 10 to 90 nm. These nanoparticle cores could encapsulate hydrophobic drugs such as doxorubicin (DOX), and the unreacted thiol and acrylate groups could be used for drug conjugation or labeling. Thus, the nanoparticles provide a multifunctional platform for drug delivery. In vivo studies showed that the larger nanoparticles (about 83.7 nm) had a much longer blood-circulation time and better tumor-targeting efficiency. One of our most important findings was that the drug encapsulated in the crosslinked nanoparticles, even though little was released at pH 7.4 under in vitro conditions, had much faster blood clearance than the nanoparticles’ carrier, suggesting that drug release in the bloodstream was significant.
研究领域:
药学
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生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2016
·
IF 1.733
Xiaoxiong Han,Dan Chen,Jing Sun,Jinsong Zhou,Duan Li,Feirong Gong,Yaling Shen
Cabazitaxel (CTX) is a second-generation semisynthetic taxane that demonstrates antitumor activity superior to docetaxel. However, the low aqueous solubility of CTX has hampered its use as a therapeutic agent. In this work, CTX-loaded N-t-butoxycarbonyl-L-phenylalanine end-capped monomethyl poly (ethylene glycol)-block-poly (D,L-lactide) (mPEG-PLA-Phe(Boc)/CTX) micelles were prepared to improve the solubility of CTX while retaining its superior stability before accessing the tumor site. The mPEG-PLA-Phe(Boc)/CTX micelles showed excellent stability in vitro compared with mPEG-PLA/CTX micelles. When stored at 25 °C, the mPEG-PLA/CTX micelles tended to aggregate within 1 h, whereas the mPEG-PLA-Phe(Boc)/CTX micelles were uniformly transparent even after three weeks. Dilution of mPEG-PLA/CTX micelles widened their size distribution and decreased the encapsulation efficiency, while significant change was not found in mPEG-PLA-Phe(Boc)/CTX micelles, even when diluted 1000-fold. Pharmacokinetic results in Sprague–Dawley rats indicated that, compared with Jevtana®, intravenous administration of mPEG-PLA-Phe(Boc)/CTX micelles stably retained the CTX in plasma with 26.03-fold larger of the area under the time–concentration curve, 2.13-fold longer of the half-life, and 9.99-fold higher of the maximum concentration. In conclusion, mPEG-PLA-Phe(Boc) micelle may be a potential nanocarrier not only to improve the solubility of CTX but also to prolong the blood circulation time, which results in improved biological activity.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Yang Li,Jianfeng Gao,Shuping Wang,Shijun Li,Xiaowen Hou,Yanna Pan,Jialu Gao,Xue Qiao,Zhiquan Tian,Deliang Chen,Hai Deng,Zixin Deng,Xuechuan Hong,Yuling Xiao
Nanocarriers hold great promise for the controlled release of therapeutic payloads to target organs/tissues and extended duration of anticancer agents in the bloodstream. However, limited data on their in vivo pharmacokinetics and delivery process hamper clinical applications. Here we report a series of micellar nanocarriers self-assembled from new-generation thiophenthiadiazole (TTD)-based NIR-II fluorophores HLAnP ( n = 1–4) for simultaneous bioimaging and drug delivery. The NIR-II HLA4P nanocarrier displays exceptional non-fouling performance, minimal immunogenicity, ultralong blood half-life, and high tumor accumulation even with different administration routes. When used as a drug carrier, HLA4P with encapsulated doxorubicin (DOX) realized accurate tumor targeting and continuous real-time in vivo NIR-II tracking of drug delivery and therapy, showing a sustained release rate, improved therapeutic effect, and diminished cardiotoxicity as compared to free DOX. This study provides a new perspective on the design of dual-functional NIR-II fluorophores for diagnostic and therapeutic applications.
研究领域:
生物医学工程
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药学
·
分子影像学
✓ 已验证
DOI
高影响因子
Science of Advanced Materials
·
2016
·Vol. 8
·期 8
·1617-1627
·
IF 1.812
Wen Zhen,Su Jun-Qing,Chen Qing,Chen Li-Di
To improve the physicochemical and pharmacokinetic properties, solid lipid nanoparticles (SLNs) modified with (Polyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG2000-DSPE) were prepared using glyceryl monostearate as a lipid carrier and resveratrol as a model
drug. Compared to ordinary SLNs, SLNs doped with low amount of PEG2000-DSPE [m(PEG2000-DSPE):m(lipids) = 1:5, w/w] exhibited improved physicochemical and pharmacokinetic properties, including higher entrapment efficiency (above 80%), smaller particle size (approximately 100 nm), more
distinguished drug release at low pH values (pH < 6.0), and longer drug circulation in vivo. According to the characterizations performed, the DSPE moiety was doped into lipid matrix to form a PEG2000-DSPE/lipid eutectic dopant, inhibiting lipid polymorphism transformation
from α-form to β-form, thereby preventing drug expulsion from the lipid. The dopant contained lattice defects, allowing for the incorporation of more resveratrol. Resveratrol was released in a sustained and pH-sensitive pattern due to nanoparticles destabilization
induced by partial protonation of PEG2000-DSPE. PEG chains distributed on the nanoparticle surface caused steric hindrance and “stealth” properties, thus maintaining dispersion stability and extending circulation time of nanoparticles. These results confirm that PEG2000-DSPE modification
effects are attributable to the matrix and surface structures of nanoparticles, which consist of a core containing DSPEinduced lattice defects and a shell coated with PEG chains.
研究领域:
药剂学
·
生物材料学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Juanjuan Peng,Yun Sun,Lingzhi Zhao,Yongquan Wu,Wei Feng,Yanhong Gao,Fuyou Li
Nanoparticles that circulate in the bloodstream for a prolonged period of time have important biomedicine applications. However, no example of lanthanide-based nanoparticles having a long-term circulation bloodstream has been reported to date. Herein, we report on difunctional radioactive and upconversion nanoparticles (UCNP) coated with polyphosphoric acid ligand, that is ethylenediamine tetramethylenephosphonic acid (EDTMP), for an application in single-photon emission computed tomography (SPECT) blood pool imaging. The structure, size and zeta-potential of the EDTMP-coated nanoparticles (EDTMP-UCNP) are verified using transmission electron microscopy and dynamic light scattering . Injection of radioisotope samarium-153-labeled EDTMP-UCNP (EDTMP-UCNP: 153 Sm) into mice reveal superior circulation time compared to control nanoparticles coated with citric acid (cit-UCNP: 153 Sm) and 153 Sm complex of EDTMP (EDTMP- 153 Sm). The mechanism for the extended circulation time may be attributed to the adhesion of EDTMP-UCNP on the membrane of red blood cells (RBCs). In vivo toxicity results show no toxicity of EDTMP-UCNP at the dose of 100 mg/kg, validating its safety as an agent for blood pool imaging. Our results provide a new strategy of nanoprobe for a long-term circulation bloodstream by introducing polyphosphoric acid as surface ligand.
研究领域:
生物医学工程
·
放射医学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Zhuojun Yan,Mengmeng Yao,Zhongming Zhao,Qi Yang,Rui Liu,Baijun Liu,Xueyu Wang,Liming Chen,Hong Zhang,Yuping Wei,Fanglian Yao,Junjie Li
Blood-contact medical devices are indispensable for clinical interventions, yet their susceptibility to thrombosis and bacterial infections poses substantial risks to treatment efficacy and patient well-being. This study introduces a polysulfobetaine/alginate-Cu II (SAC) zwitterionic hydrogel coating on polyurethane (PU) surfaces. This approach retains the superhydrophilic and antifouling nature of pSBMA while conferring the antibacterial effects of copper ions. Meanwhile, the copper alginate network intertwines with the polysulfobetaine (pSBMA) network, enhancing its mechanical properties and overcoming inherent weaknesses, thereby improving coating durability. Compared to the substrate, the SAC hydrogel coating significantly reduces thrombus adhesion mass by approximately 81.5% during extracorporeal blood circulation and effectively prevents bacterial biofilm formation even in a high-concentration bacterial milieu over 30 days. Moreover, the results from an isolated blood circulation model in New Zealand white rabbits affirm the impressive anticoagulant efficacy of the SAC hydrogel coating. The findings suggest that this hydrogel coating and its application method hold promise as a solution for blood-contact material surface modification to address thrombosis and bacterial biofilm formation simultaneously.
研究领域:
生物材料
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生物医学工程
·
血液相容性
·
抗菌技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2013
·
IF 5.371
Hongjun Gao,Jie Xiong,Tangjian Cheng,Jinjian Liu,Liping Chu,Jianfeng Liu,Rujiang Ma,Linqi Shi
The miserable targeting performance of nanocarriers for cancer therapy arises largely from the rapid clearance from blood circulation and the major accumulation in the organs of the reticuloendothelial system (RES), leading to inefficient enhanced permeability and retention (EPR) effect after intravenous injection (i.v.). Herein, we reported an efficient method to prolong the blood circulation of nanoparticles and decrease their deposition in liver and spleen. In this work, we fabricated a series of mixed shell micelles (MSMs) with approximately the same size, charge and core composition but with varied hydrophilic/hydrophobic ratios in the shell through spontaneously self-assembly of block copolymers poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLys) and poly(N-isopropylacrylamide)-block-poly(aspartic acid) (PNIPAM-b-PAsp) in aqueous medium. The effect of the surface heterogeneity on the in vivo biodistribution was systematically investigated through in vivo tracking of the 125I-labeled MSMs determined by Gamma counter. Compared with single PEGylated micelles, some MSMs were proved to be significantly efficient with more than 3 times lower accumulation in liver and spleen and about 6 times higher concentration in blood at 1 h after i.v.. The results provide us a novel strategy for future development of long-circulating nanocarriers for efficient cancer therapy.
研究领域:
药学
·
纳米技术
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Wei Zhang,Yanwen Xu,Rongjun Guo,Peiling Zhuang,Huixia Hong,Hui Tan,Mingfeng Wang
Designing an efficient nanocarrier to target multiple types of cancer remains a major challenge in the development of cancer nanomedicines. The majority of systemically administered nanoparticles (NPs) are rapidly cleared by the liver, resulting in poor tumor-targeting efficiency and severe side effects. Here, we present a delicately tailored design and synthesis of fluorescent bottle-brush polymers and screen nine derived NPs, each varying in size and surface coatings, for tumor imaging and targeted delivery. Our optimized polymer bearing (oligo(ethylene glycol) methyl ether methacrylate) in the side chains shows reduced macrophage uptake, prolonged blood-circulation time (up to 27 h), and exceptionally high accumulation in the tumor compared to the liver, elucidating an immune-evasion-induced tumor-targeting mechanism. High tumor accumulation significantly improved the antitumor efficacy. The outstanding tumor-targeting ability has been further validated across five distinct tumor models, including orthotopic glioblastoma and pancreatic cancer, which demonstrate the universality of our polymeric nanocarrier for tumor-targeting delivery.
研究领域:
纳米医学
·
癌症研究
·
聚合物科学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
Cell Reports Medicine
·
2024
·
IF 11.7
Shiyi Zuo,Tian Liu,Lingxiao Li,Hezhen Xu,Jiayu Guo,Qing Wang,Yinxian Yang,Zhonggui He,Jin Sun,Bingjun Sun
Dimeric prodrug nanoassemblies (DPNAs) stand out as promising strategies for improving the efficiency and safety of chemotherapeutic drugs. The success of trisulfide bonds (-SSS-) in DPNAs makes polysulfide bonds a worthwhile focus. Here, we explore the comprehensive role of tetrasulfide bonds (-SSSS-) in constructing superior DPNAs. Compared to trisulfide and disulfide bonds, tetrasulfide bonds endow DPNAs with superlative self-assembly stability, prolonged blood circulation, and high tumor accumulation. Notably, the ultra-high reduction responsivity of tetrasulfide bonds make DPNAs a highly selective "tumor bomb" that can be ignited by endogenous reducing agents in tumor cells. Furthermore, we present an "add fuel to the flames" strategy to intensify the reductive stress at tumor sites by replenishing exogenous reducing agents, making considerable progress in selective tumor inhibition. This work elucidates the crucial role of tetrasulfide bonds in establishing intelligent DPNAs, alongside the combination methodology, propelling DPNAs to new heights in potent cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2024
·
IF 8.4
Ting He,Xiaoyun Wang,Zhaoyun Sun,Jiangwei Chen,Yangming Cheng,Qiang Chen,Rizhi Chen,Qingguo Li,Zhaoliang Cui
Extracorporeal membrane oxygenation (ECMO) system is a life-supporting technique that plays an important role in cardiopulmonary failure or heart transplantation. Blood passes through the oxygenator to expel carbon dioxide (CO 2 ) produced during the metabolic processes while supplementing the blood with oxygen (O 2 ) to maintain the patient's life. As the key part of the oxygenator, the membranes come into direct contact with the blood for gases exchange. Therefore, membranes should possess excellent hemocompatibility to inhibit thrombosis and hemolysis. In this work, an antithrombotic coating was constructed on the surface of poly-4-methyl-1-pentene (PMP) hollow fiber membranes based on the co-deposition of zwitterionic polymer and dopamine to reduce the protein adsorption and improve hemocompatibility of the pristine PMP membranes. The experimental results were confirmed that the protein adsorption and the clotting time of the modification coating on the surface of PMP hollow fiber membranes were 16.3 μg/cm 2 and 643 s, which were 70.58 % lower and 36.8 % higher than that of the commercial PMP hollow fiber membranes (55.4 μg/cm 2 and 470 s), respectively. Test devices of in vitro blood circulation and in vivo circulation in animals were established to evaluate blood compatibility and the blood-gas exchange performance of as-prepared membrane modules, respectively, the evaluation conditions of which are similar to those of the real ECMO system. Meanwhile, the corresponding results exhibited that the poly (sulfobetaine methacrylate) (PSBMA) modified coating had good oxygenation performance and biosafety, implying that the zwitterionic polymer could provide excellent hemocompatibility for gas-blood exchange membranes in ECMO systems.
研究领域:
生物医学工程
·
材料科学
·
血液动力学
·
医疗器械
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）