PDF(Pubmed)
Abstract：
UNASSIGNED: The design of delivery tools that efficiently transport drugs into cells remains a major challenge in drug development for most pathological conditions. Triple-negative breast cancer (TNBC) is a very aggressive subtype of breast cancer with poor prognosis and limited effective therapeutic options.
UNASSIGNED: In TNBC treatment, chemotherapy remains the milestone, and doxorubicin (Dox) represents the first-line systemic treatment; however, its non-selective distribution causes a cascade of side effects. To address these problems, we developed a delivery platform based on the self-assembly of amphiphilic peptides carrying several moieties on their surfaces, aimed at targeting, enhancing penetration, and therapy.
UNASSIGNED: Through a single-step self-assembly process, we used amphiphilic peptides to obtain nanofibers decorated on their surfaces with the selected moieties. The surface of the nanofiber was decorated with a cell-penetrating peptide (gH625), an EGFR-targeting peptide (P22), and Dox bound to the cleavage sequence selectively recognized and cleaved by MMP-9 to obtain on-demand drug release. Detailed physicochemical and cellular analyses were performed.
UNASSIGNED: The obtained nanofiber (NF-Dox) had a length of 250 nm and a diameter of 10 nm, and it was stable under dilution, ionic strength, and different pH environments. The biological results showed that the presence of gH625 favored the complete internalization of NF-Dox after 1h in MDA-MB 231 cells, mainly through a translocation mechanism. Interestingly, we observed the absence of toxicity of the carrier (NF) on both healthy cells such as HaCaT and TNBC cancer lines, while a similar antiproliferative effect was observed on TNBC cells after the treatment with the free-Dox at 50 µM and NF-Dox carrying 7.5 µM of Dox.
UNASSIGNED: We envision that this platform is extremely versatile and can be used to efficiently carry and deliver diverse moieties. The knowledge acquired from this study will provide important guidelines for applications in basic research and biomedicine.
UNASSIGNED: In TNBC treatment, chemotherapy remains the milestone, and doxorubicin (Dox) represents the first-line systemic treatment; however, its non-selective distribution causes a cascade of side effects. To address these problems, we developed a delivery platform based on the self-assembly of amphiphilic peptides carrying several moieties on their surfaces, aimed at targeting, enhancing penetration, and therapy.
UNASSIGNED: Through a single-step self-assembly process, we used amphiphilic peptides to obtain nanofibers decorated on their surfaces with the selected moieties. The surface of the nanofiber was decorated with a cell-penetrating peptide (gH625), an EGFR-targeting peptide (P22), and Dox bound to the cleavage sequence selectively recognized and cleaved by MMP-9 to obtain on-demand drug release. Detailed physicochemical and cellular analyses were performed.
UNASSIGNED: The obtained nanofiber (NF-Dox) had a length of 250 nm and a diameter of 10 nm, and it was stable under dilution, ionic strength, and different pH environments. The biological results showed that the presence of gH625 favored the complete internalization of NF-Dox after 1h in MDA-MB 231 cells, mainly through a translocation mechanism. Interestingly, we observed the absence of toxicity of the carrier (NF) on both healthy cells such as HaCaT and TNBC cancer lines, while a similar antiproliferative effect was observed on TNBC cells after the treatment with the free-Dox at 50 µM and NF-Dox carrying 7.5 µM of Dox.
UNASSIGNED: We envision that this platform is extremely versatile and can be used to efficiently carry and deliver diverse moieties. The knowledge acquired from this study will provide important guidelines for applications in basic research and biomedicine.
摘要：
■有效地将药物运输到细胞中的输送工具的设计仍然是大多数病理状况下药物开发中的主要挑战。三阴性乳腺癌（TNBC）是一种侵袭性非常强的乳腺癌亚型，预后差，有效的治疗选择有限。
■在TNBC治疗中，化疗仍然是一个里程碑,多柔比星（Dox）代表一线全身治疗；然而，它的非选择性分布会导致一连串的副作用。为了解决这些问题,我们开发了一种基于两亲性肽在其表面携带几个部分的自组装的递送平台，旨在瞄准，增强穿透力，和治疗。
■通过单步自组装过程，我们使用两亲性肽来获得在其表面上装饰有选定部分的纳米纤维。纳米纤维的表面装饰有细胞穿透肽（gH625），EGFR靶向肽（P22），和Dox结合到被MMP-9选择性识别和切割的切割序列以获得按需药物释放。进行了详细的物理化学和细胞分析。
■所得纳米纤维(NF-Dox)的长度为250nm,直径为10nm,它在稀释下是稳定的，离子强度,和不同的pH环境。生物学结果表明，gH625的存在有利于NF-Dox在MDA-MB231细胞中1h后的完全内化。主要通过易位机制。有趣的是,我们观察到载体（NF）对健康细胞（如HaCaT和TNBC癌细胞系）没有毒性，而在用50µM的游离Dox和携带7.5µMDox的NF-Dox处理后，对TNBC细胞观察到类似的抗增殖作用。
■我们设想该平台是极其通用的，可用于有效地携带和递送不同的部分。从这项研究中获得的知识将为基础研究和生物医学应用提供重要的指导。
■在TNBC治疗中，化疗仍然是一个里程碑,多柔比星（Dox）代表一线全身治疗；然而，它的非选择性分布会导致一连串的副作用。为了解决这些问题,我们开发了一种基于两亲性肽在其表面携带几个部分的自组装的递送平台，旨在瞄准，增强穿透力，和治疗。
■通过单步自组装过程，我们使用两亲性肽来获得在其表面上装饰有选定部分的纳米纤维。纳米纤维的表面装饰有细胞穿透肽（gH625），EGFR靶向肽（P22），和Dox结合到被MMP-9选择性识别和切割的切割序列以获得按需药物释放。进行了详细的物理化学和细胞分析。
■所得纳米纤维(NF-Dox)的长度为250nm,直径为10nm,它在稀释下是稳定的，离子强度,和不同的pH环境。生物学结果表明，gH625的存在有利于NF-Dox在MDA-MB231细胞中1h后的完全内化。主要通过易位机制。有趣的是,我们观察到载体（NF）对健康细胞（如HaCaT和TNBC癌细胞系）没有毒性，而在用50µM的游离Dox和携带7.5µMDox的NF-Dox处理后，对TNBC细胞观察到类似的抗增殖作用。
■我们设想该平台是极其通用的，可用于有效地携带和递送不同的部分。从这项研究中获得的知识将为基础研究和生物医学应用提供重要的指导。
