Lauryl-NrTP6 lipopeptide self-assembled nanorods for nuclear-targeted delivery of doxorubicin†

IF 5.8 3区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Nanoscale Pub Date : 2025-01-15 DOI:10.1039/D4NR04068F
Amanda Phungula, Sofia Zuffi, Sunisa Thongsom, Paolo Di Gianvincenzo, Santiago Gimenez Reyes, Ana Beatriz Caribé dos Santos Valle, Frederico Pittella, Fernando Albericio, Beatriz G. de la Torre and Sergio E. Moya
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引用次数: 0

Abstract

Targeted delivery offers solutions for more efficient therapies with fewer side effects. Here, lipopeptides (LPs) prepared by conjugation of the nuclear-targeting peptide analogue H-YKQSHKKGGKKGSG-NH2 (NrTP6) and two lauric acid chains are used to encapsulate the chemotherapeutic agent doxorubicin (DX) through a solvent-exchange protocol. LPs spontaneously form nanosized rod-like assemblies in phosphate buffer. DX is trapped in the peptide regions of the assemblies. Confocal laser scanning microscopy shows that the peptide assemblies translocate into the nucleus. Cytotoxicity studies over 72 h in A549 and HeLa cancer cell lines show less toxicity for the LP encapsulated DX than for free DX. In contrast, subtoxic doses of encapsulated DX are more effective than free DX in avoiding colony formation over 14 days, with a complete absence of colonies for the LP-encapsulated DX. The results show a more efficient and slow delivery of DX to the nucleus through LP encapsulation, paving the way for the use of lower DX doses as a chemotherapeutic agent.

Abstract Image

Abstract Image

用于核靶向递送阿霉素的月桂酰基nrtp6脂肽自组装纳米棒
靶向递送提供了更有效的治疗方案,副作用更少。在这里,通过溶剂交换协议,将核靶向肽类似物h - ykqshkkkggkkgsg - nh2 (NrTP6)和两条月桂酸链偶联制备的脂肽(LPs)用于包封化疗药物阿霉素(DX)。LPs在磷酸盐缓冲液中自发形成纳米棒状组件。DX被困在组装体的肽区。共聚焦激光扫描显微镜显示,肽组装转移到细胞核。对A549和HeLa癌细胞进行72小时的细胞毒性研究表明,LP包封DX的毒性低于游离DX。相比之下,在14天内,亚毒性剂量的封装DX比游离DX更有效地避免了菌落的形成,而lp封装的DX完全没有菌落。结果表明,通过LP包封,DX更有效、更缓慢地传递到细胞核,为使用较低剂量的DX作为化疗药物铺平了道路。
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来源期刊
Nanoscale
Nanoscale CHEMISTRY, MULTIDISCIPLINARY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
12.10
自引率
3.00%
发文量
1628
审稿时长
1.6 months
期刊介绍: Nanoscale is a high-impact international journal, publishing high-quality research across nanoscience and nanotechnology. Nanoscale publishes a full mix of research articles on experimental and theoretical work, including reviews, communications, and full papers.Highly interdisciplinary, this journal appeals to scientists, researchers and professionals interested in nanoscience and nanotechnology, quantum materials and quantum technology, including the areas of physics, chemistry, biology, medicine, materials, energy/environment, information technology, detection science, healthcare and drug discovery, and electronics.
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