{"title":"胶体iscom的双重作用:一种使用Box-Behnken设计的乳腺癌管理优化方法","authors":"Drashti Desai, Pravin Shende","doi":"10.1007/s10544-022-00625-z","DOIUrl":null,"url":null,"abstract":"<div><p>Neuropeptide Y (NPY) occurs in G-protein-coupled receptors and offers targeted effects at the active sites for therapeutic action in various conditions like depression, stress, obesity and cancer. Immune stimulating complexes (ISCOMs) associate peptides with the lipid systems for enhancing antigen targeting to provide site-specific action and B-cell response. The present study focused on the encapsulation of NPY in ISCOMs to comprise dual action in the form of immunity modulation and management of breast cancer by arresting G0/G1 phase. The colloidal ISCOMs were prepared by coupling method and further optimized by Box-Behnken design of Design of Experiment (DoE) software. The NPY-loaded ISCOMs (formulation ISCN) were characterized by various parameters with higher % encapsulation efficiency of 87.99 ± 1.87% and <i>in-vitro</i> release of 84.16±3.2% of NPY for 24 h. The study of MTT assay on MCF-7 cell line for formulation ISCN exhibited a significant decrease in the cell growth of 66.41±4.7% at 10 µg/mL compared to plain NPY (52.21±0.04%). The MCF-7 cells showed a significant reduction in cytokine levels in the presence of formulation ISCN wherein T<sub>H</sub>1(TNF-α) and T<sub>H</sub>2(IL-10) levels were found to be 25.12±3.11 pg/mL and 35.76±4.23 pg/mL, respectively. The cell cycle study demonstrated that significant cells were blocked in the G0/G1 phase with 57.8±3.02% of cell apoptosis using formulation ISCN. The formulation ISCN was found to prolong t<sub>1/2</sub> and increase AUC than plain NPY via intravenous administration due to complex formation with phospholipid. Hence, ISCOMs-based NPY system will be a promising approach for dual action as immunomodulation and anticancer effects by controlling the release of NPY.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"24 3","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2022-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Dual-action of colloidal ISCOMs: an optimized approach using Box-Behnken design for the management of breast cancer\",\"authors\":\"Drashti Desai, Pravin Shende\",\"doi\":\"10.1007/s10544-022-00625-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Neuropeptide Y (NPY) occurs in G-protein-coupled receptors and offers targeted effects at the active sites for therapeutic action in various conditions like depression, stress, obesity and cancer. 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引用次数: 1
摘要
神经肽Y (NPY)发生在g蛋白偶联受体中，并在活性位点提供靶向作用，用于治疗各种疾病，如抑郁、压力、肥胖和癌症。免疫刺激复合物(ISCOMs)将多肽与脂质系统结合起来，增强抗原靶向性，提供位点特异性作用和b细胞应答。目前的研究重点是在ISCOMs中包封NPY，通过阻断G0/G1期来实现免疫调节和乳腺癌管理的双重作用。采用耦合法制备胶体iscom，并用实验设计软件Box-Behnken设计对其进行优化。不同参数表征了NPY负载ISCOMs(制剂ISCN)的包封率为87.99±1.87%，体外24 h NPY释放量为84.16±3.2%。在MCF-7细胞株的MTT试验中，制剂ISCN在10µg/mL浓度下的细胞生长比普通NPY(52.21±0.04%)显著降低66.41±4.7%。MCF-7细胞在配方ISCN的作用下，细胞因子水平显著降低，其中TH1(TNF-α)和TH2(IL-10)水平分别为25.12±3.11 pg/mL和35.76±4.23 pg/mL。细胞周期研究表明，在G0/G1期显著细胞被ISCN制剂阻断，细胞凋亡率为57.8±3.02%。由于与磷脂形成复合物，与静脉给药的普通NPY相比，ISCN配方延长了t1/2，增加了AUC。因此，基于iscoms的NPY系统将是一种很有前途的方法，通过控制NPY的释放来实现免疫调节和抗癌的双重作用。
Dual-action of colloidal ISCOMs: an optimized approach using Box-Behnken design for the management of breast cancer
Neuropeptide Y (NPY) occurs in G-protein-coupled receptors and offers targeted effects at the active sites for therapeutic action in various conditions like depression, stress, obesity and cancer. Immune stimulating complexes (ISCOMs) associate peptides with the lipid systems for enhancing antigen targeting to provide site-specific action and B-cell response. The present study focused on the encapsulation of NPY in ISCOMs to comprise dual action in the form of immunity modulation and management of breast cancer by arresting G0/G1 phase. The colloidal ISCOMs were prepared by coupling method and further optimized by Box-Behnken design of Design of Experiment (DoE) software. The NPY-loaded ISCOMs (formulation ISCN) were characterized by various parameters with higher % encapsulation efficiency of 87.99 ± 1.87% and in-vitro release of 84.16±3.2% of NPY for 24 h. The study of MTT assay on MCF-7 cell line for formulation ISCN exhibited a significant decrease in the cell growth of 66.41±4.7% at 10 µg/mL compared to plain NPY (52.21±0.04%). The MCF-7 cells showed a significant reduction in cytokine levels in the presence of formulation ISCN wherein TH1(TNF-α) and TH2(IL-10) levels were found to be 25.12±3.11 pg/mL and 35.76±4.23 pg/mL, respectively. The cell cycle study demonstrated that significant cells were blocked in the G0/G1 phase with 57.8±3.02% of cell apoptosis using formulation ISCN. The formulation ISCN was found to prolong t1/2 and increase AUC than plain NPY via intravenous administration due to complex formation with phospholipid. Hence, ISCOMs-based NPY system will be a promising approach for dual action as immunomodulation and anticancer effects by controlling the release of NPY.
期刊介绍：
Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology.
General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules.
Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.
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