Vaccines
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2024
·Vol. 13
·期 1
·25
·
IF 5.2
Siyuan Deng,Han Shao,Hongtao Shang,Lingjin Pang,Xiaomeng Chen,Jingyi Cao,Yi Wang,Zhao Zhao
Background/Objectives:The endosomal escape of lipid nanoparticles (LNPs) is crucial for efficient mRNA-based therapeutics. Here, we present a cationic polymeric micelle (cPM) as a safe and potent co-delivery system with enhanced endosomal escape capabilities.Methods:We synthesized a cationic and ampholytic di-block copolymer, poly (poly (ethylene glycol)4-5methacrylatea-co-hexyl methacrylateb)X-b-poly(butyl methacrylatec-co-dimethylaminoethyl methacrylated-co-propyl acrylatee)Y(p(PEG4-5MAa-co-HMAb)X-b-p(BMAc-co-DMAEMAd-co-PAAe)Y), via reversible addition–fragmentation chain transfer polymerization. The cPMs were then formulated using the synthesized polymer by the dispersion–diffusion method and characterized by dynamic light scattering (DLS) and cryo-transmission electron microscopy (CryoTEM). The membrane-destabilization activity of the cPMs was evaluated by a hemolysis assay. We performed an in vivo functional assay of firefly luciferase (Fluc) mRNA using two of the most commonly studied LNPs, SM102 LNP and Dlin-MC3-DMA LNPs.Results:With a particle size of 61.31 ± 0.68 nm and a zeta potential of 37.76 ± 2.18 mV, the cPMs exhibited a 2–3 times higher firefly luciferase signal at the injection site compared to the control groups without cPMs following intramuscular injection in mice, indicating the high potential of cPMs to enhance the endosomal escape efficiency of mRNA-LNPs.Conclusions:The developed cPM, with enhanced endosomal escape capabilities, presents a promising strategy to improve the expression efficiency of delivered mRNAs. This approach offers a novel alternative strategy with no modifications to the inherent properties of mRNA-LNPs, preventing any unforeseeable changes in formulation characteristics. Consequently, this polymer-based nanomaterial holds immense potential for clinical applications in mRNA-based vaccines.
研究领域:
药学科学
·
分子生物学
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药物递送系统
·
基因治疗
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2024
·
IF 4.4
Siyuan Yu,Xian Shao,Tong Wu,Zheng Liu,Pei Yu,Jinfeng Xing
In order to achieve long-term and controllable release of anti-tumor drugs at specific sites, temperature/pH responsive nanoparticles encapsulating 5-fluorouracil and methotrexate in situ are prepared through dispersion photopolymerization under green LED irradiation. The physicochemical properties of nanoparticles are characterized by scanning electron microscopy, Fourier transform infrared, dynamic light scattering, thermogravimetric/differential scanning calorimetry, and X-ray diffraction. In vitro drug release at different temperatures and pH values is examined to ascertain the release pattern of two drugs, which can be well described by Korsmeyer–Peppas kinetic model. The cytotoxicity evaluation illustrates that the tumor cells could be more effectively killed by the drug-loaded nanoparticles, and the improved therapeutic effect is attributed to the controllable and sustainable drug release as well as the enhanced cellular uptake. The blood safety and good biocompatibility of nanoparticles are further confirmed by hemolysis assay, indicating the prepared nanoparticles are potential candidates for effective tumor treatment.
研究领域:
纳米技术
·
药学
·
材料科学
·
生物医学工程
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2016
·
IF 1.733
Tingting Xu,Fang Peng,Tao Zhang,Bo Chi,Hong Xu,Chun Mao,Shuaihui Feng
Poly(γ-glutamic acid) (γ-PGA) powder was usually used as hemostatic agent because of its excellent physical properties of water-absorption and water-locking. However, if γ-PGA absorbs enough water, how about its blood compatibility? Here, the other side of the coin was investigated. The anticoagulant properties of γ-PGA were characterized by in vitro coagulation tests, hemolytic assay, platelet adhesion, and platelet activation. Moreover, cytotoxicity experiments of γ-PGA were also carried out by MTT assay. Results indicated that the sufficient water-absorbed γ-PGA has good anticoagulant property and non-cytotoxicity. It means γ-PGA has good anticoagulant property, non-cytotoxicity. If γ-PGA has absorbed enough water, it can be used as an anticoagulation biomaterial. With double effects (coagulation and anticoagulation), the γ-PGA with desirable bioproperties can be readily tailored to cater to various biomedical applications.
研究领域:
生物材料
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止血
·
抗凝
·
生物相容性
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2024
·Vol. 19
·期 3
·035013
·
IF 3.9
Jieqiong Ding,Jie Tan,Xiaohang Peng,Liyuan Cheng,Weiling Huang,Binhua Luo
A novel biodegradable amphiphilic triblock copolymer, polyphosphate, polyethylene glycol, and polylactic acid (PAEEP-PEG-PLLA), was synthesized by twice ring-opening polymerization and triphenylphosphine (TPP) was grafted onto the block copolymer to synthesize a carrier material TPP-PAEEP-PEG-PLLA, which was identified by 1H-nuclear magnetic resonance (1H-NMR) spectroscopy. The TPP-PAEEP-PEG-PLLA nanoparticles encapsulated with ursolic acid (UA) were prepared by the emulsion-solvent evaporation method and characterized by dynamic light scattering. The mitochondrial targeting ability of fluorescently labeled nanoparticles was evaluated by laser confocal microscopy. The average particle size and surface charge of the UA -loaded nanoparticle solution were 180.07 ± 1.67 nm and +15.57 ± 1.33 mV, respectively. The biocompatibility of nanoparticles was briefly evaluated by erythrocyte hemolysis assay. In vitro cell proliferation assay and scratch migration assay were performed to compare the difference in anti-tumor effect between UA and UA nanoparticles. The results showed that TPP-modified triblock copolymers had good mitochondrial targeting and improved the low bioavailability of UA, and UA nanoparticles exhibited more pronounced anti-tumor capabilities. In summary, the results suggested that our UA nanoparticles were a promising drug-targeted delivery system for the treatment of tumors.
研究领域:
药学
·
纳米技术
·
癌症研究
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2013
·
IF 4.093
Wen-Wen Yue,Hui-Juan Li,Tao Xiang,Hui Qin,Shu-Dong Sun,Chang-Sheng Zhao
Zwitterionic polymer of poly(sulfobetaine methacrylate) (PSBMA) was grafted from polysulfone (PSf) membrane via surface-initiated atom transfer radical polymerization (SI-ATRP). The polysulfone- graft -poly(sulfobetaine methacrylate) (PSf- g -PSBMA) membrane was characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), attenuated total reflectance-Fourier transform infrared spectra (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and static water contact angle (WCA) measurement. The membrane showed excellent protein antifouling property though the water flux decreased to some content; nevertheless, the protein rejection ratio of the modified membrane was not change. The biocompatibility of the membrane was characterized by protein adsorption, hemolysis assay, platelet adhesion, plasma recalcification time, activated partial thromboplastin time (APTT), thrombin time (TT) and cytotoxicity experiments, and the results indicated that the modified PSf membrane had good blood compatibility and cytocompatibility.
研究领域:
材料科学
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生物医学工程
·
高分子化学
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膜技术
✓ 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）