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A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer

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Acta Pharmaceutica Sinica B 2022年第1期12卷 378-393页

作者： Dandan Sun Yifang Zou Liu Song Shulan Han Hao Yang Di Chu Yun Dai Jie Ma Caitriona M.O’Driscoll Zhuo Yu Jianfeng Guo School of Pharmaceutical Sciences Jilin UniversityChangchun 130021China Laboratory of Cancer Precision Medicine The First Hospital of Jilin UniversityChangchun 130021China Pharmacodelivery Group School of PharmacyUniversity College CorkCork T12 YT20Ireland Department of Hepatopathy Shuguang HospitalAffiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer(CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment(TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death(ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3(Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin(QTN) that elicited reactive oxygen species(ROS). To amelioratein vivo delivery barriers associated with chemotherapeutic drugs, a folate(FA)-targeted polyethylene glycol(PEG)-modified amphiphilic cyclodextrin nanoparticle(NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation(***) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the *** achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

关键词： nano drug delivery system Chemotherapy Immunotherapy Combination therapy Immunogenic cell death Reactive oxygen species Tumor microenvironment Colorectal cancer

Intelligent lesion blood–brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1987-1999页

作者： Xueqin He Xiaorong Wang Lianyi Yang Zhihang Yang Wenqi Yu Yazhen Wang Rui Liu Meiwan Chen Huile Gao Key Laboratory of drug-Targeting and drug delivery system of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China

The treatment of Alzheimer's disease(AD)is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier(BBB)permeability and unsatisfactory intra-brain distribution of ***,we established an ibuprofen and FK506 encapsulated drug co-delivery system(Ibu&FK@RNPs),which can target the receptor of advanced glycation endproducts(RAGE)and response to the high level of reactive oxygen species(ROS)in *** is highly and specifically expressed on the lesion neurovascular unit of AD,this property helps to improve targeting specificity of the system and reduce unselective distribution in normal ***,these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of *** a result,the cognition of AD mice was significantly improved and the quantity of Aβplaques was *** was also alleviated with structural regeneration and functional recovery of ***,the neuroinflammation dominated by NF-κB pathway was significantly inhibited with decreased NF-κB and IL-1βin the ***,Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD *** it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection.

关键词： Receptor for advanced glycation end products ROS-responsive Blood‒brain barrier transcytosis Alzheimer’s disease drug combination Anti-neuroinflammation Neuroprotection nano drug delivery system

Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 49-68页

作者： Xumei Ouyang Yu Liu Ke Zheng Zhiqing Pang Shaojun Peng Zhuhai Institute of Translational Medicine Zhuhai Precision Medical CenterZhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Zhuhai 519000China Key Laboratory of Smart drug delivery Ministry of EducationDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China School of Materials Science and Engineering Dongguan University of TechnologyDongguan 523808China

nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side *** several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease *** glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological ***,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical *** polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and *** nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated *** impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical *** realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical ***,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their ***,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

关键词： Zwitterionic polymer nano drug delivery system Biological barrier Targeting delivery Disease treatment

Insights on drug and gene delivery systems in liver fibrosis

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Asian Journal of Pharmaceutical Sciences 2023年第2期18卷 4-27页

作者： Kunj Vyas Mayur M Patel Department of Pharmaceutics Institute of PharmacyNirma University SG HighwayGujarat 382481India

Complications of the liver are amongst the world’s worst *** fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to *** creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of *** breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in ***-based delivery systems are regarded to be effective but they have not been adequately researched for liver *** a result,the capability of nanoparticles in hepatic delivery was *** approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in *** genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are *** summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.

关键词： Liver fibrosis Gene delivery system nano drug delivery system Cirrhosis Targeted delivery system Vector

Enrichment of nano delivery platforms for mRNA-based nanotherapeutics

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Medical Review

Medical Review 2023年第4期3卷 356-361页

作者： Xiao Liu Xu Zhang Jiulong Li Huan Meng Department of Gastroenterology Beijing HospitalNational Center of GerontologyInstitute of Geriatrics MedicineChinese Academy of Medical SciencesBeijingChina CAS Key Laboratory for Biomedical Effects of nanomaterials and nanosafety and CAS Center for Excellence in nanoscience National Center for nanoscience and Technology BeijingChina University of Chinese Academy of Sciences BeijingChina CAS Key Laboratory for Biomedical Effects of nanomaterials and nanosafety and CAS Center for Excellence in nanoscience National Center for nanoscience and Technology 11 ZhongguancunbeiyitiaoHaidian DistrictBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Lipid-based nanoparticles(LNP)have shown significant progress in delivering mRNA for therapeutics,particularly with the success of coronavirus disease 2019(COVID-19)***,there are still challenges,such as organ-specific targeting,sustained protein expression,immunogenicity,and storage that need to be ***,there is interest in developing additional nano drug delivery systems(DDS)to complement LNP *** of these include polymer,lipid-polymer hybrid,organic/inorganic hybrid nanostructure,and inorganic *** our opinion,LNP technology may not be suitable for every disease scenario in categories such as infection disease,cancer,pulmonary disease,autoimmune disorders and genetic rare disease(among others).This is because different diseases may require distinct administration routes,doses,and treatment durations,as well as considerations for biological barriers that may lower the efficacy and/or exert safety *** this perspective,we will highlight the need and potential for enhancing the diversity of nano delivery platforms for mRNA-based nanotherapeutics.

关键词： high throughput screening mRNA nano/bio interface nano drug delivery system non-LNP nanocarrier nanosafety

Integrated combination delivery of IDO inhibitor and paclitaxel for cancer treatment

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Journal of Chinese Pharmaceutical Sciences 2021年第1期30卷 1-16页

作者： Dakuan Wang Bo Peng Mengmeng Qin Minghui Li Ge Song Bing He Hua Zhang Wenbing Dai Qiang Zhang Xiangbao Meng Huan Meng Xueqing Wang Beijing Key Laboratoiy of Molecular Pharmaceutics New Drug Delivefy SystemsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Chemical Biology School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

In order to realize the combination of chemotherapy and immunotherapy,a reduction-responsive paclitaxel(PTX)prodrug PEG-SS-PTX was synthesized and used as a carrier to encapsulate IDO inhibitor CY-1-4 for preparing PEG-SS-PTX/CY-1-4 ***-SS-PTX/CY-1-4 NPs were evaluated by cytotoxicity,immunogenic cell death(ICD)induction ability and anti-tumor *** light scattering(DLS)results showed that the size of PEG-SS-PTX/CY-1-4 NPs was about 149 *** vitro experiments indicated that its cytotoxicity was in a concentration-dependent manner,and it induced the ICD of B16-F10 *** vivo studies in melanoma mouse model indicated that PEG-SS-PTX/CY-1-4 NPs significantly inhibited the tumor growth and reduced the expression of IDO in tumor ***,it increased the rate of CD8+T cells in the *** summary,PEG-SS-PTX/CY-1-4 NPs achieved good anti-tumor effects and reduced the dose of chemotherapy drugs,which was a safe and effective combined delivery system.

关键词： Chemotherapy Immunotherapy Combination drug delivery nano drug delivery system IDO activity inhibition Immunogenic cell death