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Research advancements in nanoparticles and cell-based drug delivery systems for the targeted killing of cancer cells

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Oncology Research 2025年第1期33卷 27-44页

作者： MERYEM A.ABDESSALEM SIRIN A.ADHAM Department of Biology College of ScienceSultan Qaboos UniversityMuscat123Oman

Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized *** smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal *** nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs *** these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle ***-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer *** review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer *** covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer *** detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.

关键词： Drug delivery Cancer Nanoparticles Liposomes Micelles combination therapies Targeted therapy Precision medicine Tumor microenvironment(TME)

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Non-apoptotic cell death-based cancer therapy:Molecular mechanism,pharmacological modulators,and nanomedicine

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3567-3593页

作者： Xuan Wang Peng Hua Chengwei He Meiwan Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoSAR 999078China

As an emerging cancer therapeutic target,non-apoptotic cell death such as ferroptosis,necroptosis and pyroptosis,etc.,has revealed significant potential in cancer treatment for bypassing apoptosis to enhance the undermined therapeutic efficacy triggered by apoptosis resistance.A variety of anticancer drugs,synthesized compounds and natural products have been proven recently to induce non-apoptotic cell death and exhibit excellent anti-tumor ***,the convergence of nanotechnology with functional materials and biomedicine science has provided tremendous opportunities to construct non-apoptotic cell death-based nanomedicine for innovative cancer *** are not only employed in targeted delivery of non-apoptotic inducers,but also used as therapeutic components to induce non-apoptotic cell death to achieve efficient tumor *** review first introduces the main characteristics,the mechanism and various pharmacological modulators of different non-apoptotic cell death forms,including ferroptosis,necroptosis,pyroptosis,autophagy,paraptosis,lysosomal-dependent cell death,and ***,we comprehensively review the latest progresses of nanomedicine that induces various forms of non-apoptotic cell death and focus on the nanomedicine targeting different pathways and ***,the combination therapies of non-apoptotic cell death with photothermal therapy,photodynamic therapy,immunotherapy and other modalities are ***,the challenges and future perspectives in this regard are also discussed.

关键词： Non-apoptotic cell death Ferroptosis Necroptosis Pyroptosis Autophagy Nanomedicine combination therapies Anticancer

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Immunotherapy for hepatocellular carcinoma:Current status and future perspectives

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World Journal of Gastroenterology 2023年第6期29卷 1054-1075页

作者： Deepa S Mandlik Satish K Mandlik Heena B Choudhary Department of Pharmacology BVDUPoona College of PharmacyPune 411038MaharashtraIndia Department of Pharmaceutics BVDUPoona College of PharmacyPune 411038MaharashtraIndia

Hepatocellular carcinoma(HCC)is one of the world’s deadliest and fastestgrowing tumors,with a poor *** develops in the context of chronic liver *** resection,surgery(liver transplantation),trans-arterial chemoembolization,radioembolization,radiofrequency ablation and chemotherapy are common treatment options for HCC,however,they will only assist a limited percentage of *** treatments for advanced HCC are ineffective and aggravate the underlying liver *** promising preclinical and early-phase clinical trials for some drugs,existing systemic therapeutic methods for advanced tumor stages remain limited,underlining an unmet clinical *** current years,cancer immunotherapy has made significant progress,opening up new treatment options for ***,on the other hand,has a variety of causes and can affects the body’s immune system via a variety of *** the speedy advancement of synthetic biology and genetic engineering,a range of innovative immunotherapies,such as immune checkpoint inhibitors[anti-programmed cell death-1(PD-1),anti-cytotoxic T lymphocyte antigen-4,and anti-PD ligand 1 cell death antibodies],therapeutic cancer vaccines,engineered cytokines,and adoptive cell therapy have all been used for the treatment of advanced *** this review,we summarize the present clinical and preclinical landscape of immunotherapies in HCC,critically discuss recent clinical trial outcomes,and address future perspectives in the field of liver cancer.

关键词： Hepatocellular carcinoma Immunotherapy Immune checkpoint inhibitors Alpha-fetoprotein Cancer vaccine combination therapies

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Crosstalk between the B7/CD28 and EGFR pathways:Mechanisms and therapeutic opportunities

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Genes & Diseases 2022年第5期9卷 1181-1193页

作者： Xiaoxin Ren Yixian Li Christopher Nishimura Xingxing Zang Department of Microbiology and Immunology Albert Einstein College of MedicineNew YorkNY 10461USA Division of Pediatric Hematology/Oncology/Transplant and Cellular Therapy Children's Hospital at MontefioreBronxNY 10467USA Department of Medicine Albert Einstein College of MedicineNew YorkNY 10461USA Department of Urology Albert Einstein College of MedicineNew YorkNY 10461USA

Somatic activating mutations in the epidermal growth factor receptor(EGFR)are one of the most common oncogenic drivers in cancers such as non-small-cell lung cancer(NSCLC),metastatic colorectal cancer,glioblastoma,head and neck cancer,pancreatic cancer,and breast ***-targeted agents against EGFR signaling pathways have shown robust clinical efficacy,but patients inevitably experience acquired *** immune checkpoint inhibitors(ICIs)targeting PD-1/PD-L1 have exhibited durable anti-tumor responses in a subset of patients across multiple cancer types,their efficacy is limited in cancers harboring activating gene alterations of *** studies have demonstrated that upregulation of new B7/CD28 family members such as B7-H3,B7x and HHLA2,is associated with EGFR signaling and may contribute to resistance to EGFR-targeted therapies by creating an immunosuppressive tumor microenvironment(TME).In this review,we discuss the regulatory effect of EGFR signaling on the PD-1/PD-L1 pathway and new B7/CD28 family member *** these interactions may inform combination therapeutic strategies and potentially overcome the current challenge of resistance to EGFR-targeted *** also summarize clinical data of anti-PD-1/PD-L1 therapies in EGFR-mutated cancers,as well as ongoing clinical trials of combination of EGFR-targeted therapies and anti-PD-1/PD-L1 immunotherapies.

关键词： combination therapies EGFR Immune checkpoint blockade New B7/CD28 members PD-1/PD-L1 pathway

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Update of latest data for combined therapy for esophageal cancer using radiotherapy and immunotherapy:A focus on efficacy,safety,and biomarkers

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Chinese Journal of Cancer Research 2023年第5期35卷 483-500页

作者： Shuping Cheng Butuo Li Jinming Yu Linlin Wang Department of Radiation Oncology Shandong Cancer Hospital Affiliated to Shandong First Medical UniversityJinan 250117China Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China Research Unit of Radiation Oncology Chinese Academy of Medical SciencesJinan 250117China

Esophageal cancer usually has a poor *** the significant breakthrough with tumor immunotherapy,an increasing number of clinical studies have demonstrated that the combination of radiotherapy and immune checkpoint inhibitors(ICIs)may have a synergistic effect and good outcome in esophageal *** studies of immunoradiotherapy(iRT)for esophageal cancer have proliferated enormously from 2021 to the ***,a summary of the efficacy and toxicity of combined therapy to guide esophageal cancer treatment in clinical practice is *** this review,we integrate the latest data to analyze and assess the efficacy and safety of iRT for esophageal *** addition,we discuss better predictive biomarkers,therapeutic options for specific populations,and other challenges to identify directions for future research design.

关键词： Esophageal cancer immunoradiotherapy combination therapies

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Six-year analysis of key monitoring for bacterial strain distribution and antibiotic sensitivity in a hospital

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World Journal of Clinical Cases 2023年第30期11卷 7294-7301页

作者： Zong-Ying Li Dong Yang Chong-Hua Hao Clinical Laboratory Changzhi People’s HospitalChangzhi 046000Shanxi ProvinceChina Clinical Laboratory Shanxi Provincial People’s Hospital(The Fifth Clinical Medical College of Shanxi Medical University)Taiyuan 030001Shanxi ProvinceChina

BACKGROUND With the widespread use of antimicrobial drugs,bacterial resistance has become a significant problem,posing a serious threat to public *** prevalence of clinical infection strains in hospitals and their drug sensitivities are key to the appropriate use of antibiotics in clinical *** To identify prevalent bacteria and their antibiotic resistance profiles in a hospital setting,thereby guiding effective antibiotic usage by *** Specimens from across the institution were collected by the microbiology *** VITEK 2 compact fully automatic analyzer was used for bacterial identification and antibiotic sensitivity testing,and the WHONET5.6 software was utilized for statistical *** A total of 12062 bacterial strains of key monitoring significance were *** aureus demonstrated widespread resistance to penicillin,but none of the strains were resistant to vancomycin or ***,219 strains of methicillin-resistant coagulase-negative staphylococci and 110 strains of methicillin-resistant Staphylococcus aureus were *** faecalis showed moderate resistance to the third-generation quinolones ciprofloxacin and levofloxacin,but its resistance to nitrofurantoin and tetracycline was *** faecium displayed significantly lower resistance to third-and fourthgeneration quinolones than Enterococcus *** resistance of two key monitoring strains,Escherichia coli and Klebsiella pneumoniae,to piperacillin/tazobactam was 5%-8%.However,none of the Escherichia coli and Klebsiella pneumoniae strains were resistant to *** resistance of Acinetobacter baumannii to piperacillin/sulbactam was nearly 90%.Nonetheless,the resistance to tigecycline was low,and Pseudomonas aeruginosa demonstrated minimal resistance in the antibiotic sensitivity test,maintaining a resistance of<10%to the cephalosporin antibiotics cefotetan and cefoperazone over the last 6 *** resista

关键词： Antibiotic sensitivity test Monitoring bacterial antibiotic resistance Antimicrobial drugs Antimicrobial stewardship combination therapies Antibiotic stewardship

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Developing immunotherapy strategies in the treatment of prostate cancer

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Asian Journal of Urology 2016年第4期3卷 278-285页

作者： James L.Gulley Ravi A.Madan Genitourinary Malignancies Branch National Cancer InstituteNational Institutes of HealthBethesdaMDUSA

The clinical development of immunotherapy has gained significant impetus in recent years across the field of medical *** preclinical and clinical data have demonstrated the potential of immune-based treatments to augment anti-tumor immune *** one of the first modern immunotherapies approved in prostate cancer and multiple others in late stage development,immune treatment strategies need to be optimized to ensure the best clinical *** strategies with androgen deprivation therapy,anti-androgen therapy,radiation and chemotherapy have demonstrated the potential maximize immune response in prostate cancer *** combinations are currently being evaluated in clinical trials at every stage of prostate cancer from the newly diagnosed to the most advanced *** from these studies will provide guidance for the future clinical implementation of immunotherapy in prostate cancer.

关键词： Prostate cancer Immunotherapy combination therapies

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Novel anti-androgen receptor signaling agents:Understanding the mechanisms of resistance

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Asian Journal of Urology 2014年第1期1卷 30-39页

作者： Styliani Karanika Theodoros Karantanos Jianhua Yin Likun Li Timothy C.Thompson Department of Genitourinary Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA Department of Epidemiology Second Military Medical UniversityShanghaiChina

Prostate cancer remains an intractable threat to the lives of men *** deaths from prostate cancer(PCa)in the United States have declined in recent years,in other parts of the world Pca mortality is *** introduction of 2nd generation antiandrogen receptor agents into the therapeutic armamentarium for metastatic castrationresistant prostate cancer(mCRPC)has resulted in modestly increased survival advantages as demonstrated by initial clinical ***,analysis of the molecular pathways affected by these agents may lead to new insight into mechanisms of resistance that drive mCRPC,including proliferation and survival signaling pathways that are derepressed by maximum repression of androgen *** therapies that involve anti-AR signaling agents together with agents that target these pathways establish a paradigm for the development of more effective treatment of *** this review,we briefly summarize the current clinical trial literature with regard to novel anti-AR signaling agents such as abiraterone acetate and *** discuss observational data that point to mechanisms of resistance that emerged from these *** further present and discuss recent experimental studies that address the mechanisms of resistance to these ***,we discuss novel and rational therapeutic approaches,including combination therapy,for patients with mCRPC.

关键词： Prostate cancer Castration-resistant prostate cancer Anti-androgen receptor agents combination therapies

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combination therapy in cancer:effects of angiogenesis inhibitors on drug pharmacokinetics and pharmacodynamics

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Chinese Journal of Cancer 2016年第12期35卷 647-656页

作者： Ilaria Fuso Nerini Marta Cesca Francesca Bizzaro Raffaella Giavazzi Department of Oncology IRCCS-Mario Negri Institute for Pharmacological ResearchVia La Masa 1920156 MilanItaly

Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor(VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far from clear. The most widespread explanation is enhanced delivery of therapeutics due to vascular remodeling, lower interstitial pressure, and increased blood flow. While the antiangiogenic efects on vascular morphology have been fairly consistent in both preclinical and clinical settings, the improvement of tumor vessel function is debated. This review focuses on the efect of anti-VEGF therapy on tumor microenvironment morphology and functions, and its therapeutic beneits when combined with other therapies. The uptake and spatial distribution of chemotherapeutic agents into the tumor after anti-VEGF are examined.

关键词： combination therapies Angiogenesis inhibitors Drug delivery Tumor microenvironment

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Is combined lipid-regulating therapy safe and feasible for the very old patients with mixed dyslipidemia?

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Journal of Geriatric Cardiology 2013年第4期10卷 349-354页

作者： Xiao Zou Quan-Jin Si The First Department of the Geriatric Cardiology Chinese PLA General Hospital NO.28 Fuxing Road Beijing 100853 China

OBJECTIVES: To detect the efficacy and safety of combined lipid-regulating therapies in the very old patients with mixed dyslipidemia and determine an appropriate therapy for them。 METHODS: Four hundred and fifty patients aged over 75 with mixed dyslipidemia were divided into five groups according to different combination therapies。 Lipid levels and drug related adverse events were tested during the study。 RESULTS: Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were reduced in every group compared to baseline: statin + ezetimibe: -30.0% and -55.5%; statin + policosanol: -31.1% and -51.2%; statin + fibrates: -23.7% and -44.6%; statin + niacin: -25.2% and -43.0%; and niacin + fibrates: -11。3% and -23.5%。 The target achievement rates of LDL-C all exceeded 50%, except in niacin + fibrates (42.0%); statin + ezetimibe: 57.0%; statin + policosanol: 56.0%; statin + niacin: 52.0%; and statin + fibrates: 50.0%。 However, overall, the niacin + fibrates group was the most effective in decreasing triglyceride (TG) and increasing high-density lipoprotein cholesterol (HDL-C) as follows: niacin + fibrates: -39.3% and 28.6%; statin + fibrates: -29.3% and 18.4%; statin + niacin: -18.5% and 16.7%; statin + ezetimibe: -17.1% and 7.1%; and statin + policosanol: -15.6% and 9.5%。 The achievement rates of TG and HDL-C levels in niacin + fibrates (58.0% and 39.0%) were better than the other four groups: statin + niacin (34.0% and 34.0%), statin + fibrates (43.0% and 28.0%), statin + policosanol (30.0% and 24.0%) and statin + ezetimibe (28.0% and 25.0%)。 Patients in all five groups experiencing drug adverse events were only 2% and no severe adverse events occurred。 CONCLUSIONS: Statin + ezetimibe was the most effective group in lowering TC and LDL-C levels, while niacin + fibrates was the most effective in decreasing TG and increasing HDL-C levels。 The commonly used combined lipid-regulating therapies with common dosages in this study were all quite safe and fea

关键词： Elderly patients Mixed dyslipidemia combination therapies Safety

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