PDF(Pubmed)
Abstract：
UNASSIGNED: New treatment modalities for hepatocellular carcinoma (HCC) are desperately critically needed, given the lack of specificity, severe side effects, and drug resistance with single chemotherapy. Engineered bacteria can target and accumulate in tumor tissues, induce an immune response, and act as drug delivery vehicles. However, conventional bacterial therapy has limitations, such as drug loading capacity and difficult cargo release, resulting in inadequate therapeutic outcomes. Synthetic biotechnology can enhance the precision and efficacy of bacteria-based delivery systems. This enables the selective release of therapeutic payloads in vivo.
UNASSIGNED: In this study, we constructed a non-pathogenic Escherichia coli (E. coli) with a synchronized lysis circuit as both a drug/gene delivery vehicle and an in-situ (hepatitis B surface antigen) Ag (ASEc) producer. Polyethylene glycol (CHO-PEG2000-CHO)-poly(ethyleneimine) (PEI25k)-citraconic anhydride (CA)-doxorubicin (DOX) nanoparticles loaded with plasmid encoded human sulfatase 1 (hsulf-1) enzyme (PNPs) were anchored on the surface of ASEc (ASEc@PNPs). The composites were synthesized and characterized. The in vitro and in vivo anti-tumor effect of ASEc@PNPs was tested in HepG2 cell lines and a mouse subcutaneous tumor model.
UNASSIGNED: The results demonstrated that upon intravenous injection into tumor-bearing mice, ASEc can actively target and colonise tumor sites. The lytic genes to achieve blast and concentrated release of Ag significantly increased cytokine secretion and the intratumoral infiltration of CD4/CD8+T cells, initiated a specific immune response. Simultaneously, the PNPs system releases hsulf-1 and DOX into the tumor cell resulting in rapid tumor regression and metastasis prevention.
UNASSIGNED: The novel drug delivery system significantly suppressed HCC in vivo with reduced side effects, indicating a potential strategy for clinical HCC therapy.
UNASSIGNED: In this study, we constructed a non-pathogenic Escherichia coli (E. coli) with a synchronized lysis circuit as both a drug/gene delivery vehicle and an in-situ (hepatitis B surface antigen) Ag (ASEc) producer. Polyethylene glycol (CHO-PEG2000-CHO)-poly(ethyleneimine) (PEI25k)-citraconic anhydride (CA)-doxorubicin (DOX) nanoparticles loaded with plasmid encoded human sulfatase 1 (hsulf-1) enzyme (PNPs) were anchored on the surface of ASEc (ASEc@PNPs). The composites were synthesized and characterized. The in vitro and in vivo anti-tumor effect of ASEc@PNPs was tested in HepG2 cell lines and a mouse subcutaneous tumor model.
UNASSIGNED: The results demonstrated that upon intravenous injection into tumor-bearing mice, ASEc can actively target and colonise tumor sites. The lytic genes to achieve blast and concentrated release of Ag significantly increased cytokine secretion and the intratumoral infiltration of CD4/CD8+T cells, initiated a specific immune response. Simultaneously, the PNPs system releases hsulf-1 and DOX into the tumor cell resulting in rapid tumor regression and metastasis prevention.
UNASSIGNED: The novel drug delivery system significantly suppressed HCC in vivo with reduced side effects, indicating a potential strategy for clinical HCC therapy.
摘要：
■迫切需要肝细胞癌（HCC）的新治疗方式，鉴于缺乏特异性，严重的副作用,和单一化疗耐药。工程化细菌可以靶向并在肿瘤组织中积累，诱导免疫反应，充当药物输送工具。然而,传统的细菌疗法有局限性，如药物装载能力和货物释放困难，导致治疗结果不足。合成生物技术可以提高基于细菌的递送系统的精度和功效。这使得治疗有效负载在体内的选择性释放成为可能。
■在这项研究中，我们构建了一种非致病性大肠杆菌(E.大肠杆菌）与同步裂解回路作为药物/基因递送载体和原位（乙型肝炎表面抗原）Ag（ASEC）生产者。将负载有质粒编码的人硫酸酯酶1（hsulf-1）酶（PNP）的聚乙二醇（CHO-PEG2000-CHO）-聚（乙烯亚胺）（PEI25k）-柠康酸酐（CA）-多柔比星（DOX）纳米颗粒锚定在ASEC（ASEC@PNP）的表面。合成并表征了复合材料。在HepG2细胞系和小鼠皮下肿瘤模型中测试了ASEC@PNP的体外和体内抗肿瘤作用。
■结果表明，静脉注射荷瘤小鼠后，ASEC可以主动靶向和定植肿瘤部位。裂解基因实现Ag的爆发和集中释放显着增加了细胞因子的分泌和肿瘤内CD4/CD8T细胞的浸润，引发了特定的免疫反应。同时,PNP系统将hsulf-1和DOX释放到肿瘤细胞中，从而导致快速的肿瘤消退和预防转移。
■新型药物递送系统在体内显着抑制HCC，副作用减少，表明临床肝癌治疗的潜在策略。
■在这项研究中，我们构建了一种非致病性大肠杆菌(E.大肠杆菌）与同步裂解回路作为药物/基因递送载体和原位（乙型肝炎表面抗原）Ag（ASEC）生产者。将负载有质粒编码的人硫酸酯酶1（hsulf-1）酶（PNP）的聚乙二醇（CHO-PEG2000-CHO）-聚（乙烯亚胺）（PEI25k）-柠康酸酐（CA）-多柔比星（DOX）纳米颗粒锚定在ASEC（ASEC@PNP）的表面。合成并表征了复合材料。在HepG2细胞系和小鼠皮下肿瘤模型中测试了ASEC@PNP的体外和体内抗肿瘤作用。
■结果表明，静脉注射荷瘤小鼠后，ASEC可以主动靶向和定植肿瘤部位。裂解基因实现Ag的爆发和集中释放显着增加了细胞因子的分泌和肿瘤内CD4/CD8T细胞的浸润，引发了特定的免疫反应。同时,PNP系统将hsulf-1和DOX释放到肿瘤细胞中，从而导致快速的肿瘤消退和预防转移。
■新型药物递送系统在体内显着抑制HCC，副作用减少，表明临床肝癌治疗的潜在策略。
