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Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors

Acta Pharmaceutica Sinica B 2022年第12期12卷 4501-4518页

作者： Yuling Mao Xiudan Wang Caishun Chen qinfu zhao Yanfeng Liu Jinghai Zhang Siling Wang Department of Pharmaceutics School of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Department of Biomedical Engineering School of Medical DevicesShenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Bio-pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China

Utilization of the intestinal lymphatic pathway will allow extraordinary gains in lymph and tumors cascade-targeted delivery of oral drugs and awakening the innate/adaptive immunity of the body and the lesion microenvironment,in addition to improving oral bioavailability relative to other means of delivery of oral ***,inspired by the specific invasion route of intestinal microorganisms,we pioneered an immune-awakening Saccharomyces-inspired mesoporous silicon nanoparticle(yMSN)for the ingenious cascade-targeted delivery of therapeutic cancer vaccines and antitumor drugs to lymph and tumors via the intestinal lymphatic ***,yMSN high-loaded tumor-specific antigens(OVA,11.9%)and anti-tumor drugs(Len,28.6%)with high stability,namely Len/OVA/yMSN,efficiently co-delivered OVA and Len to their desired target ***,yMSN concomitantly awakened the innate antitumor immunity of dendritic cells and macrophages,strengthening vaccine-induced adaptive immune responses and reversing macrophage-associated immunosuppression in the tumor ***,Len/OVA/yMSN treatment resulted in excellent synergistic antitumor efficacy and long-term antitumor memory in OVA-Hepa1-6-bearing *** high-performance nanocarrier provides a novel approach for lesion-targeting delivery of oral drugs accompanied with awakening of the innate/adaptive immunity of the lesion environment,and also represents a novel path for the oral delivery of diverse therapeutic agents targeting other lymph-mediated diseases.

关键词： Oral delivery Saccharomyces-inspired Immune-awakening nanoparticles Intestinal lymphatic pathway Vaccine delivery Cascade-targeted delivery Awakening the innate/adaptive immunity Co-delivery

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MSNCs and MgO-MSNCs as drug delivery systems to control the adsorption kinetics and release rate of indometacin

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Asian Journal of Pharmaceutical Sciences 2019年第3期14卷 275-286页

作者： Xin Zheng Shuang Feng Xiudan Wang Zhenning Shi Yuling Mao qinfu zhao Siling Wang Department of Pharmaceutics School of PharmacyShenyang Pharmaceutical UniversityShenyang110016China School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang110016China

Mesoporous silica cocoon materials(MSNCs) and MgO doped mesoporous silica cocoons(MgO-MSNCs) with the cocoon-like hierarchical morphology and different alkalinities were synthesized as carriers for acidic drugs. Indomethacin(IMC) was selected as a model drug and loaded into carriers. All materials and the drug-loaded samples were characterized by nitrogen adsorption, FTIR spectroscopy, transmission electron microscopy(TEM), powder X-Ray diffraction(XRD) and differential scanning calorimetry(DSC). The effect of the Mg/Si molar ratio on the kinetics and equilibrium of IMC adsorption on MgO-MSNCs was thoroughly examined, and it was found that the increase in the Mg/Si molar ratio resulted in an increasing IMC adsorption rate due to the increased affinity between alkaline MgO-MSNCs and weak acid IMC. The adsorption kinetics fitted a pseudo second-order model well. The Freundlich isotherm showed a better fit, indicating that the coverage of IMC on the surface of MgO-MSNCs was heterogeneous. The maximum adsorption capacity of adsorbent was calculated by the Langmuir isotherm equation. The Temkin equation provided further support that the IMC adsorption on MgO-MSNCs was dominated by a chemisorption process. MgO-MSNCs also have the advantage of allowing an adjustment of the drug release rate of weak acid drug. The cytotoxicity assay indicated good biocompatibility of MgO-MSNCs. Our research on MgO-MSNCs carriers demonstrated their potential therapeutic benefit for safe and effective management of IMC adsorption and in vitro release.

关键词： MSNCs MgO-MSNCs Indometacin Adsorption Release rate

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Author correction to“Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors”[Acta Pharmaceutica Sinica B 12(2022)4501-4518]

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1478-1482页

作者： Yuling Mao Xiudan Wang Caishun Chen qinfu zhao Yanfeng Liu Jinghai Zhang Siling Wang Department of Pharmaceutics School of PharmacyShenyang Pharmaceutical University103 Wenhua RoadShenyang110016China Department of Biomedical Engineering School of Medical DevicesShenyang Pharmaceutical University103 Wenhua RoadShenyang110016China School of Life Science and Bio-pharmaceutics Shenyang Pharmaceutical University103 Wenhua RoadShenyang110016China

The authors regret that there is an error in the article Fig.9D1 due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading,and also a mislabled error in the supp... 详细信息

关键词： correction supporting proof

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A bioactive nanocomposite integrated specific TAMs target and synergistic TAMs repolarization for effective cancer immunotherapy

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Bioactive Materials 2024年第8期38卷 472-485页

作者： Wei Gu Wen Guo Zhishuang Ren Yimeng Zhang Meiqi Han qinfu zhao Yikun Gao Yuling Mao Siling Wang Department of Pharmaceutics School of PharmacyShenyang Pharmaceutical University103 Wenhua RoadShenyangLiaoning Province110016China School of Life Sciences and Biopharmaceuticals Shenyang Pharmaceutical University103 Wenhua RoadShenyangLiaoning Province110016China

Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising cancer immunotherapy ***,their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of ***,a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer *** mesoporous silica nanoparticles(CMSN)are fabricated to encapsulate photosensitizer-Indocyanine Green(ICG)to improve their *** ginseng-derived exosome(GsE)was coated on the surface of ICG/CMSN for targeting TAMs,as well as repolarizing TAMs concurrently,named ICG/CMSN@*** expected,with the synergism of ICG and GsE,ICG/CMSN@GsE exhibited better stability,mild generation of ROS,favorable specificity toward M2-like macrophages,enhancing drug retention in tumors and superior TAMs repolarization potency,then exerted a potent antitumor *** vivo,experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor *** together,by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform,ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.

关键词： Ginseng-derived exosome Colloidal mesoporous silica nanoparticles Tumor-associated macrophages TAMs-specific targeting delivery Repolarizing TAMs

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Mesoporous carbon as a carrier for celecoxib:The improved inhibition effect on MDA-MB-231 cells migration and invasion

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Asian Journal of Pharmaceutical Sciences 2014年第2期9卷 82-91页

作者： Wenquan Zhu qinfu zhao Xin Zheng Zhiwen Zhang Tongying Jiang Yaping Li Siling Wang School of Pharmaceutics Shenyang Pharmaceutical UniversityNo.103 Wenhua RoadShenyangLiaoning Province 110016China Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesNo.501 Haike RoadShanghai 201203China

In the current study,mesoporous carbon(MC)with pore volume(1.53 cm3/g)and pore size(9.74 nm)was successfully prepared as a carrier for celecoxib(CEL).Celecoxib was loaded into the pore channels of MC using three different methods:solvent evaporation method,absorption method and physical mixing ***-state characterization methods,such as SEM,TEM,BET,DSC and XRD were used to systematically investigate the process of the drug loading *** tests were performed to examine the effects of MC on the release of ***,the cytotoxicity,wound healing,migration and invasion experiments were carried out to measure the contribution of MC to the anti-tumor metastasis ability of celecoxib on MDA-MB-231 *** results showed that CEL could be kept in a non-crystalline state when they were incorporated into the MC using the solvent evaporation method or absorption *** dissolution rate of CEL released from MCS(Mesoporous carbon e Celecoxib e Solvent evaporation method)and MCA(Mesoporous carbon e Celecoxib e Absorption evaporation method)was all significantly higher than that of pure *** cumulative release for MCS within the 5 min was up to 51.86%.MCS enhanced the inhibitory effect of CEL on the migration and invasion of MDAMB-231 cells.

关键词： Mesoporous carbon Carrier Dissolution Migration Invasion

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Development of phosphonate-terminated magnetic mesoporous silica nanoparticles for pH-controlled release of doxorubicin and improved tumor accumulation

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Asian Journal of Pharmaceutical Sciences 2014年第6期9卷 317-323页

作者： Erxi Che Long Wan Ying Zhang qinfu zhao Xiling Han Jia Li Jia Liu Siling Wang Department of Pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China

In this study,phosphonate-terminated magnetic mesoporous nanoparticles(pMMSNs)was designed by incorporation of MNPs in the center of mesoporous silica nanoparticles(MSNs)and followed by grafting phosphonate group on to the surface of *** carrier exhibited a typical superparamagnetic feature and the saturation magnetization was 4.89 emu/g measured by vibrating sample magnetometer(VSM).pMMSNs had a spherical morphology and a pore size of 2.2 ***2 adsorption-desorption analysis,pMMSNs had a surface area of 613.4 m^(2)/g and a pore volume of 0.78 cm^(3)/*** modification improved the colloidal stability of MMSNs,and the hydrodynamic diameter of pMMSNs was around 175 *** hydrophilic phosphonate group significantly enhanced the negative surface charge of MMSNs from -19.3 mV to -28.8 mV pMMSNs with more negative surface charge had a 2.3-fold higher drug loading capacity than that of *** addition,the rate and amount of release of doxorubicin(DOX)from DOX/pMMSNs was pH-dependent and increased with the decrease of *** pH 7.4,the release amount was quite low and only approximately 17wt%***5.0and3.0,the release rate increased significantly and the release amount achieved 31 wt%and 60 wt%in 48 h,*** evaluate the magnetic targeting performance ofpMMSNs,FITC labeledpMMSNswas injected into mice bearing S180 solid *** labeledpMMSNscontrolled by an external magnetic field showed higher tumor accumulation and lower normal tissue distribution.

关键词： Magnetic mesoporous silica nanoparticles Doxorubicin pH-depended release Tumor accumulation

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Recent advances in copper homeostasis-involved tumor theranostics

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Asian Journal of Pharmaceutical Sciences 2024年第5期19卷 54-87页

作者： Xinghua Ren Xinyi Luo Fuchang Wang Long Wan Xiaofan Wang Jinya Xiong Mengwei Ye Shiqiao Rui Zhu Liu Siling Wang qinfu zhao Department of Pharmaceutics School of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Wuya College of innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacy The First Hospital of China Medical UniversityShenyang 110001China Department of Pharmacy The Fourth Affiliated Hospital of China Medical UniversityShenyang 110001China School of Pharmacy China Medical UniversityShenyang 110122China

As the third essential trace element in the human body,copper plays a crucial role in various physiological processes,which lays the foundation for its broad applications in cancer *** overview of copper,including pharmacokinetics,signaling pathways,and homeostasis dysregulation,is hereby ***,cuproptosis,as a newly proposed cell death mechanism associated with copper accumulation,is analyzed and further developed for efficient cancer *** forms of Cu-based nanoparticles and their advantages,aswell as limiting factors,are ***,the unique characteristics of Cu-based nanoparticles give rise to their applications in various imaging *** addition,Cu-based nanomaterials are featured by their excellent photothermal property and ROS-associated tumor-killing potential,which are widely explored in diverse cancer therapies and combined *** the concentration of Cu^(2+)/Cu^(+)is another cancer-killing method,and chelators can meet this *** importantly,challenges and future prospects are identified for further research.

关键词： Copper homeostasis Tumor theranostics Cu-based nanoparticles Cuproptosis Chelators

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MnO2-Mesoporous Carbon Composites-based Nanoplatform Overcomes Hypoxia for The Combination of Photothermal and Photodynamic Therapy

MnO2-Mesoporous Carbon Composites-based Nanoplatform Overcom...

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2018年第十二届中国药物制剂大会

作者：李显 qinfu zhao Siling Wang School of Pharmacy Shenyang Pharmaceutical University

Photothermal therapy(PTT) and photodynamic therapy(PDT) are two main strategies of phototherapy. Since the effective uptake of photo-sensitizer agents by cancer cells is necessary for PDT and the elevated temperature mediated by PTT can increase the uptake of photosensitizer agents, the treatment efficacy might be enhanced by combining these two strategies. However, continuous oxygen consumption in inherent hypoxic tumor microenvironment would greatly hinder the efficacy of PDT. Hence, we presented a MnO-mesoporous carbon composites-based nanoplatform(Ce6/iPMC-MnO) overcomes hypoxia for the combination of photothermal and photodynamic therapy. The mesoporous carbon(MC) were used as the PTT agents and drug carriers with high loading capacity. The Chlorin e6(Ce6) was used as a photosensitizer agent to load into the mesoporous of the MC. The MnO was covered on the surface of the MC to overcome hypoxia of tumor. The PEG was grafted on the surface of the MC-MnO to improve the biocompatibility of the nanoparticle. The iRGD was used as targeting agent to target and penetrate into the tumor. As shown in TEM, the MC-COOH nanoparticles with a diameter of 100 nm were equally distributed. In vitro NIR-induced photothermal result suggested that the iPMC-MnO had good photothermal effect and excellent photothermal stability. With the increasing concentration of the HO, the fluorescence of RDPP was reduced owing to the generation of the oxygen. The result of CLSM showed that the cellular uptake of Ce6/iPMC-MnO could be enhanced compared to the free Ce6. Compared with Ce6/PMC-MnO, the Ce6/iPMC-MnO had a better tumor penetration ability. The appearance of the fluorescence signal of DCF indicated that the Ce6/iPMCMnO could generate ROS under the 660 nm laser. This work suggested that Ce6/iPMC-MnO could be explored as a nanoplatform for the combination of photothermal and photodynamic therapy.

关键词： mesoporous carbon MnO2 hypoxia photothermal photodynamic therapy

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Chylomicron-mimicked Bio-self-assembling MSNs to improve bioavailability of Oral Drugs via Promoting Lymphatic Transport

Chylomicron-mimicked Bio-self-assembling MSNs to improve bio...

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2018年第十二届中国药物制剂大会

作者：毛玉玲 qinfu zhao Da WANG Siling WANG Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University

Lymphatic transport of oral drugs allows extraordinary gains in bioavailability and efficacy through avoidance of first-pass hepatic metabolism and reservation drugs at lymphatic tissues against lymphmediated diseases. This drug absorption pathway plays a win-win role in both pharmacokinetics and pharmacodynamics for antiretroviral therapy to fully suppress HIV. Herein, with the inspiration of triglyceride digestion process in the daily diet, we engineered a triglyceride-mimicked mesoporous silica nanocarrier（namely TMCMS） to promote lymphatic transport of antiretroviral drugs. Taking lopinavir（LNV） as a model antiretroviral drug with hurdles of poor solubility, high first pass effect and off-target disposition, TMCMS vector exhibited several properties belonging to ideal nanocarriers of high drug load, amorphous dispersion and controlled release in gastrointestinal tract, and also a perfect hydrolysis performance similar to TG pre-uptake. Subsequently, TMCMS showed a serious of TG-mimetic transport features across intestinal epithelial cells: hydrolysis–re-esterification–chylomicron assembly, participating into such a biochemical process and self-assembling to a chylomicron-associated TMCMS（namely TMCMS@CM） in enterocytes. As a result, TMCMS brought 10.6 folds oral bioavailability through circumventing first-pass metabolism through lymphatic transport pathway. Our study provides evidences of using the bio-selfassembling TMCMS nanocarrier to facilitate bioavailability and efficacy via lymphatic transport of oral drugs.

关键词： lymphatic transport antiretroviral therapy oral bioavailability first-pass metabolism lymphatic target mesoporous silica nanocarrier lopinavir

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近红外和pH双重响应的介孔碳药物递送系统的制备与初步评价

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沈阳药科大学学报 2020年第6期37卷 481-487页

作者：沙天健林琳高源赵沛栩史馨语赵勤富沈阳药科大学药学院辽宁沈阳110016

目的为了提高药物疗效,降低毒副作用,研究制备了近红外(near-infrared,NIR)和pH双重响应型的介孔碳(mesoporous carbon,MCN)递送系统。方法首先以十六烷基三甲基氯化铵(cetyltrimethyl ammonium chloride,CTAC)为模板,正硅酸乙酯(ethyl orthosilicate,TEOS)为硅源,酚醛树脂为碳源制备介孔碳载体,然后用浓硫酸和过硫酸铵对载体进行羧基化修饰,最后将聚乙二醇(polyethylene glycol,PEG)修饰在MCN表面,增加载体的分散性和生物相容性。研究采用透射电镜、比表面积及孔径分布仪、Zeta电位测定等对载药体系进行表征。此外,阿霉素(adriamycin,DOX)作为模型药物,并对体系的NIR和pH响应性释放行为进行考察。结果体外升温效果显示体系具有浓度依赖性和功率依赖性。在pH 7.4磷酸盐缓冲液(PBS)中,药物释放量较低,而在pH 5.0 PBS中药物释放量增加。当在808 nm激光器照射下,药物释放呈现阶梯式增长,表现出明显的pH和NIR双重响应型释药特征。当PEG修饰在载体表面,体系的溶血百分率明显降低。结论研究构建的载药系统具有明显pH和NIR双重响应型药物释药特征,为化疗-热疗的联合应用提供了新的思路。

关键词：介孔碳阿霉素近红外响应 pH响应聚乙二醇

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