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首页> 外文期刊>Biomaterials Science >Collaborative assembly of doxorubicin and galactosyl diblock glycopolymers for targeted drug delivery of hepatocellular carcinoma
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Collaborative assembly of doxorubicin and galactosyl diblock glycopolymers for targeted drug delivery of hepatocellular carcinoma

机译：多柔比蛋白和半乳糖基二嵌段聚氨基聚合物的协同组装用于肝细胞癌的靶向药物递送

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摘要

Hepatocellular carcinoma (HCC) patients suffer from severe pain due to the serious systemic side effects and low efficiency of chemotherapeutic drugs, and it is important to develop novel drug delivery systems to circumvent these issues. In this study, a series of galactose-based glycopolymers, poly(N-(prop-2-enoyl)-beta-d-galactopyranosylamine)-b-poly(N-isopropyl acrylamide) (pGal(OH)-b-pNIPAA), were prepared through a sequential reversible addition-fragmentation chain transfer (RAFT) polymerization and tetrabutylammonium hydroxide (TBAOH)-mediated removal of acetyl groups. Hydrophilic doxorubicin hydrochloride was introduced to undergo collaborative assembly with poly(N-(prop-2-enoyl)-beta-d-peracetylated galactosamine)-b-poly(N-isopropyl acrylamide) (pGal(Ac)-b-pNIPAA) via TBAOH treatment. pGal-b-pNIPAA/doxorubicin (DOX) delivery nanoparticles (GND NPs) formed by collaborative assembly were fully characterized by NMR, TEM and FT-IR, indicating the well-controlled formation of particles with uniform size and high efficiency in terms of drug loading and encapsulation compared with conventional adsorption methods. Meanwhile, the GND NPs were observed to be rapidly disintegrated under acidic conditions and resulted in an increased release of DOX. Cellular experiments showed that pGal-b-pNIPAA/DOX is apparently an asialoglycoprotein receptor (ASGPR)-mediated target of HCC, resulting in enhanced cellular uptake to HepG2 cells and anti-tumor efficacy in vitro. Furthermore, GND NPs III exerted more sustainable and effective anti-tumor effects compared to free DOX on a transgenic zebrafish TO(Kras(G12V)) model in vivo. These results indicated that the biocompatible nanomaterials developed by collaborative assembly with galactosyl diblock glycopolymers and DOX may serve as a promising candidates for targeting therapy of HCC.
机译：肝细胞癌（HCC）患者由于严重的全身副作用和低化学治疗药物效率而患有严重的疼痛，并且重要的是开发新的药物递送系统以规避这些问题。在该研究中，一系列半乳糖基甘甘油聚合物，聚（N-（PROP-2-ENOYL）-Beta-D-半乳糖酰胺胺）-B-聚（N-异丙基丙烯酰胺）（PGAL（OH）-B-PNIPAA） ，通过顺序可逆添加 - 碎片链转移（筏）聚合和四丁基氢氧化铵（TBAOH）介导的除去乙酰基来制备。引入亲水性Doxorubi蛋白盐酸盐与聚（N-（PROP-2-ENOYL）-beta-d-peracetylated半乳糖胺）-b-聚（N-异丙基丙烯酰胺）（PGAL（AC）-B-PNIPAA）进行协同组装TBAOH治疗。通过协作组件形成的PGAL-B-PNIPAA /多柔比星（DOX）递送纳米颗粒（GND NPS）通过NMR，TEM和FT-IR完全表征，表明在药物方面具有均匀尺寸和高效率的颗粒良好控制的颗粒的形成加载和封装与常规吸附方法相比。同时，观察到GND NPS在酸性条件下快速崩解，导致DOX的释放增加。细胞实验表明，PGAL-B-PNIPAA / DOX显然是HCC的亚喹癌蛋白受体（ASGPR）介导的靶标，导致对HepG2细胞的细胞摄取和体外抗肿瘤疗效增强。此外，与在体内转基因斑马鱼（KRAS（G12V））模型中，GND NPS III施加了更可持续和有效的抗肿瘤作用，以在体内转基因斑马鱼（KRAS（G12V））模型。这些结果表明，通过与半乳糖基二嵌段甘糖聚合物和DOX开发的生物相容性纳米材料可以作为靶向HCC治疗的有希望的候选者。

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  • 来源
    《Biomaterials Science》 |2020年第1期|共12页
  • 作者

    Li Jianghua; Zhang Yang; Cai Chao; Rong Xiaozhi; Shao Meng; Li Jiarui; Yang Chendong; Yu Guangli;

  • 作者单位

    Ocean Univ China Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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