Amphiphilic mannose-6-phosphate glycopolypeptide-based bioactive and responsive self-assembled nanostructures for controlled and targeted lysosomal cargo delivery,Biomaterials Science

当前位置： X-MOL 学术 › Biomater. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Amphiphilic mannose-6-phosphate glycopolypeptide-based bioactive and responsive self-assembled nanostructures for controlled and targeted lysosomal cargo delivery
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-09-16 , DOI: 10.1039/d0bm01469a
Basudeb Mondal _{1,

2,

3,

4} , Bhawana Pandey _{4,

5,

6,

7,

8} , Nimisha Parekh _{4,

5,

6,

7,

8} , Sidharth Panda _{1,

2,

3,

4} , Tahiti Dutta _{1,

2,

3,

4} , Abinash Padhy _{1,

2,

3,

4} , Sayam Sen Gupta _{1,

2,

3,

4}

Affiliation

Receptors of carbohydrate mannose-6-phosphate (M6P) are overexpressed in specific cancer cells (such as breast cancer) and are also involved in the trafficking of mannose-6-phosphate labeled proteins exclusively onto lysosomes via cell surface M6P receptor (CI-MPR) mediated endocytosis. Herein, for the first time, mannose-6-phosphate glycopolypeptide (^M6PGP)-based bioactive and stimuli-responsive nanocarriers are reported. They are selectively taken up via receptor-mediated endocytosis, and trafficked to lysosomes where they are subsequently degraded by pH or enzymes, leading to the release of the cargo inside the lysosomes. Two different amphiphilic M6P block copolymers ^M6PGP₁₅-^APPO₄₄ and ^M6PGP₁₅-(PCL₂₅)₂ were synthesized by click reaction of the alkyne end-functionalized ^M6PGP₁₅ with pH-responsive biocompatible azide end-functionalized acetal PPO and azide end-functionalized branched PCL, respectively. In water, the amphiphilic M6P-glycopolypeptide block copolymers self-assembled into micellar nanostructures, as was evidenced by DLS, TEM, AFM, and fluorescence spectroscopy techniques. These micellar systems were competent to encapsulate the hydrophobic dye rhodamine-B-octadecyl ester, which was used as the model drug. They were stable at physiological pH but were found to disassemble at acidic pH (for ^M6PGP₁₅-^APPO₄₄) or in the presence of esterase (for ^M6PGP₁₅-(PCL₂₅)₂). These ^M6PGP based micellar nanoparticles can selectively target lysosomes in cancerous cells such as MCF-7 and MDA-MB-231. Finally, we demonstrate the clathrin-mediated endocytic pathway of the native FL-^M6PGP polymer and RBOE loaded ^M6PGP micellar-nanocarriers, and selective trafficking of MCF-7 and MDA-MB-231 breast cancer cell lysosomes, demonstrating their potential applicability toward receptor-mediated lysosomal cargo delivery.

中文翻译：

基于两亲甘露糖6-磷酸糖多肽的生物活性和响应性自组装纳米结构，可控制和靶向溶酶体货物的输送

碳水化合物甘露糖6-磷酸（M6P）的受体在特定的癌细胞（如乳腺癌）中过表达，并且还参与了甘露糖6-磷酸标记的蛋白仅通过细胞表面M6P受体（CI-MPR ）的运输。）介导的内吞作用。在此，首次报道了基于甘露糖6磷酸糖多肽（^M6P GP）的生物活性和刺激响应性纳米载体。它们通过受体介导的内吞作用被选择性吸收，并运到溶酶体中，随后它们被pH或酶降解，导致货物释放到溶酶体内。两种不同的两亲性M6P嵌段共聚物^M6P GP ₁₅ - ^APPO ₄₄和^M6P GP _15-（PCL ₂₅）₂分别通过炔末端官能化的^M6P GP ₁₅与pH响应的生物相容性叠氮化物末端官能化的缩醛PPO和叠氮化物末端官能化的支链PCL的点击反应合成。在水中，两亲性M6P-糖多肽嵌段共聚物会自组装成胶束纳米结构，这通过DLS，TEM，AFM和荧光光谱技术得以证明。这些胶束系统能够封装用作模型药物的疏水染料若丹明-B-十八烷基酯。它们在生理pH下稳定，但在酸性pH下会分解（对于^M6PGP ₁₅ -^甲PPO ₄₄）或在酯酶的存在下（对于^M6P GP ₁₅ - （PCL ₂₅）₂）。这些基于^M6P GP的胶束纳米粒子可以选择性靶向癌细胞中的溶酶体，例如MCF-7和MDA-MB-231。最后，我们证明了天然FL- ^M6P GP聚合物和RBOE加载的^M6P GP胶束-纳米载体的网格蛋白介导的内吞途径，以及MCF-7和MDA-MB-231乳腺癌细胞溶酶体的选择性转运，证明了它们潜在的适用于受体介导的溶酶体货物递送。

更新日期：2020-11-03

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11