LASERS IN MEDICAL SCIENCE
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2025
·Vol. 40
·期 1
·1-11
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IF 2.4
Ma Dan,Lu Huixiang,Zhang Hai,Liao Anru,Peng Qianrong,Yang Min
Hypoxia poses a significant challenge to the efficacy of photodynamic therapy (PDT) for cancer treatment. This study aims to design and synthesize PEGylated liposomes encapsulating MnO₂, indocyanine green (ICG), and H-chain ferritin (HFn) to potentially address hypoxia and enhance the therapeutic outcomes of PDT. PEGylated liposomes (ICG/MnO₂-HFn-mPEG-DSPE-Lip) were constructed with a rod-like structure, incorporating MnO₂ as a hypoxia-modulating agent and ICG as a photosensitizer. The drug loading capacity, stability and safety of liposomes were characterized. Singlet oxygen quantum yield (Φ Δ ) was measured under simulated tumor microenvironment conditions. In vitro phototoxicity was evaluated using A549 human lung adenocarcinoma cells. Liposomes have a high drug loading capacity, good biocompatibility and good long-term stability. Under tumor-simulated conditions, Φ Δ was significantly improved, increasing from 0.210 for free ICG to 0.507. The liposomes demonstrated remarkable phototoxic effects on A549 cells (90.5% cell death under combined PDT/PTT vs. 15% for free ICG). This nanoplatform proposes a novel strategy to overcome hypoxia-induced PDT resistance, and the enhanced efficacy may be attributed to the increased oxygen supply mediated by MnO 2 carried by HFn. These findings provide important insights for the development of next-generation therapeutic systems targeting tumor hypoxia.
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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产品关联
DOI
PubMed
高影响因子
Drug Research
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2017
·Vol. 68
·期 05
·270-279
·
IF 0
Shuoye Yang
Long-circulating liposomal delivery systems of encapsulated Coenzyme Q10 (CoQ10), a ubiquinone anti-cataract agent, were developed with different molar ratios of PEGylated lipids and/or cholesterol. The resulting samples were contrasted through observation of morphology, analysis of particle size and Zeta potential, and in vivo pharmacokinetics. A protamine aggregation method with high selectivity was developed to determine the encapsulation efficiency (EE), after which the liposome formulation was further optimized by applying a Box Behnken design (BBD) using EE as the evaluation index. The results showed that liposomes had a large, unilamellar structure, and that particle sizes of cholesterol-containing liposomes increased along with the increase of cholesterol molar percentage, while the size of PEGylated vesicles decreased slightly as PEG-lipid contents increasing. The optimum formulation and optimal values of each influencing factor were quantitatively obtained, and the measured value was highly consistent with the predicted results. In vivo evaluation performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) demonstrated that liposomal encapsulation largely prolonged half-lives and improved bioavailability for vectors prepared with either lipid component, and the liposomes composed of both cholesterol and PEG-lipid possessed the best pharmacokinetic properties. The results suggest that incorporating high contents of cholesterol and PEG modification could be a potentially useful method for enhancing the length of circulation and the sustained release effect for liposome-encapsulated chemicals.
研究领域:
药剂学
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生物医学工程
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药物代谢动力学
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DOI
PubMed
ACS Nano
·
2025
·
IF 16
Menghua Gao,Jiafeng Zhong,Xinxin Liu,Yanjun Zhao,Dingcheng Zhu,Xiaohuo Shi,Xuehan Xu,Qin Zhou,Wenjing Xuan,Yue Zhang,Yaofeng Zhou,Jianjun Cheng
Organ- and cell-specific delivery of mRNA via modular lipid nanoparticles (LNPs) is promising in treating various diseases, but targeted cargo delivery is still very challenging. Most previous work focuses on screening ionizable and helper lipids to address the above issues. Here, we report the multifacial role of PEGylated lipids in manipulating LNP-mediated delivery of mRNA to the liver. We employed the typical excipients in LNP products, including DLin-MC3-DMA, DPSC, and cholesterol. Five types of PEGylated lipids were selected, and their molar ratio was fixed at 1.5% with a constant PEG molecular weight of 2000 Da. The architecture of steric lipids dramatically affected the in vitro gene transfection, in vivo blood clearance, liver deposition, and targeting of specific cells, all of which were closely linked to the de-PEGylation rate. The fast de-PEGylation resulted in short blood circulation and high accumulation in the liver. However, the ultrafast de-PEGylation enabled the deposition of more LNPs in Kupffer cells other than hepatocytes. Surprisingly, simply changing the terminal groups of PEGylated lipids from methoxyl to carboxyl or amine could dramatically increase the liver delivery of LNPs, which might be associated with the accelerated de-PEGylation rate and enhanced LNP–cell interaction. The current work highlights the importance of manipulating steric lipids in promoting mRNA delivery, offering an alternative approach for formulating and optimizing mRNA LNPs.
研究领域:
分子生物学
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药物递送
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2020
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IF 2.734
Ning Ding,Yaxi Wang,Xiaolin Wang,Wei Chu,Tian Yin,Jingxin Gou,Haibing He,Yu Zhang,Yanjiao Wang,Xing Tang
Gemcitabine , as a nucleoside analog , has been used as first-line chemotherapy drug for many years. However, the treatment dose of gemcitabine in the clinic has been usually extremely high due to its rapid metabolism. The aim of this study was to achieve successful chemotherapy at low doses by a PEGylated liposomal delivery system. The liposomes were prepared with Lipoid S-100, Cholesterol and DSPE-PEG2000 (at a molar ratio of 9:2:0.07) by the film dispersion-extrusion-ammonium sulfate gradient method. The entrapment efficiency (EE, %) and drug loading (DL, %) of the liposomes (117.8 ± 16.85 nm) were 68.83% and 2.52%, respectively. The in vitro release study and plasma stability experiments showed the gemcitabine liposomes (GEM-Lip) was more stable than gemcitabine solutions (GEM-Sol) at pH 7.4 and in the plasma. AUC and C max of GEM-Lip were shown to be 6.20 and 16.44-fold higher than that of the solutions. The pharmacodynamics (PD) experiment in Kunming mice bearing a H22 cancer cell model showed that the tumor inhibition rate (TIR) of GEM-Lip was 6.25-fold as that of GEM-Sol when administrated intravenously. Our findings demonstrated that the preparation of GEM-Lip could effectively enhance the pharmacokinetic properties , the plasma stability and antitumor effect of gemcitabine.
研究领域:
药学
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肿瘤学
·
生物医学工程
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2017
·
IF 3.649
Jiahao Lin,Qiang Cai,Yinian Tang,Yanjun Xu,Qian Wang,Tingting Li,Huihao Xu,Shuaiyu Wang,Kai Fan,Zhongjie Liu,Yipeng Jin,Degui Lin
Highly ordered mesoporous silica nanoparticles (MSNs) with pore diameter of 2.754 nm and particle size of 115 ± 15 nm were prepared with etching method. Homogeneous PEGylated lipid bilayer with 10–15 nm thickness was coated around the surface of MSNs using film hydration method. Systematic optimization and characterization of co-encapsulation process of paclitaxel (Tax) and curcumin (Cur) into PEGylated lipid bilayer coated mesoporous silica nanoparticles (PLMSNs) were performed carrying out single factor test, associated with Box-Behnken Design. The concentration of encapsulated drugs was measured by reversed phase high performance liquid chromatography (RP-HPLC) method. Optimal factor settings were as follows: 50 mg MSNs, ratio of MSNs to lipid (w/w) = 1:1.11, and ratio of lipid to CHO (w/w) = 3.93:1. The average experimental EE Tax , EE Cur and stability score value were (77.48 ± 2.73) %, (30.70 ± 3.56) % and 4 point respectively based on the conditions mentioned above. Morphology determination of Tax-Cur-PLMSNs revealed that the composite nanoparticles were spherical particals with uniform dispersion. In vitro release experiment indicated that PLMSNs improved dissolution of Tax compared to Tax powder suspension and exhibited sustained release property. Tax-Cur-PLMSNs manifested definite and persistently promoted cytotoxic effect against canine breast cancer cells. This prolonged and enhanced activity of Tax-Cur-PLMSNs might contribute to its sustained release effect.
研究领域:
药剂学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2021
·
IF 6.598
Xianyan Qin,Liming He,Donghao Fan,Wenlang Liang,Qin Wang,Jiyu Fang
Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint inflammation and immune dysfunction. Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications, the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems. Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation. Ac2–26, a 25-amino acid peptide derived from Annexin A (a pro-resolving mediator), has shown good efficacy in the treatment of inflammatory disorders. However, the low bioavailability of Ac2–26 peptides hinders their efficacy in vivo . In this paper, we formed PEGylated lipid nanoparticles (LDNPs) by the co-assembly of l -ascorbyl palmitate (L-AP) and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE-PEG 2k ) to encapsulate and deliver Ac2–26 peptides to the arthritic rats. They showed good stability and biocompatibility. After being intravenously administrated, Ac2–26 peptide-loaded PEGylated lipid nanoparticles (ADNPs) showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites. In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology. Therefore, the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.
研究领域:
免疫学
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纳米医学
·
药理学
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Liming He,Donghao Fan,Wenlang Liang,Qin Wang,Jiyu Fang
Rheumatoid arthritis (RA) is an autoimmune disorder. It causes inflammation, swelling, and pain in the joints of the human body. Overexpressed matrix metalloproteinases (MMPs) at the inflammatory sites of RA are a target in the construction of inflammation-responsive drug delivery vehicles for enhancing the therapeutic effect of anti-inflammatory drugs in the treatment of RA. In this paper, we report MMP-responsive PEGylated lipid nanoparticles through the co-assembly of triglycerol monostearate (TGMS) and 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-poly(ethyleneglycol) (DSPE-PEG2000) in which the ester bond of TGMS is cleavable by MMPs and the PEG chain provides a stealth layer. The lipid nanoparticles show high biocompatibility, extended blood circulation, and preferential distribution in the inflammatory joints of RA. The loaded dexamethasone (Dex) can be rapidly released from the lipid nanoparticles in response to MMPs. After being intravenously administered to arthritic rats, Dex-loaded MMP-responsive PEGylated lipid nanoparticles significantly reduce the degree of joint swelling and inhibit the production of TNF-α and IL-1β in joint tissues. These results demonstrate that MMP-responsive PEGylated lipid nanoparticles are a smart drug vehicle for the treatment of RA with improved therapeutic efficacy.
研究领域:
药剂学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
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