基于DNA界面的具有多层可转换结构的一体化生物计算纳米剂。

All-in-one Biocomputing Nanoagents with Multilayered Transformable Architecture based on DNA Interfaces.

作者信息

Cherkasov Vladimir R, Mochalova Elizaveta N, Babenyshev Andrey V, Nikitin Maxim P

机构信息

Moscow Center for Advanced Studies, 20 Kulakova St, 123592, Moscow, Russia.

Sirius University of Science and Technology, 1 Olimpiyskiy Ave, 354340, Sirius, Krasnodar region, Russia.

出版信息

Theranostics. 2025 Jul 25;15(16):8451-8472. doi: 10.7150/thno.113059. eCollection 2025.

Abstract

The pathogen diversity to infiltrate the host organism highlights the demand for equally sophisticated mechanisms for their prevention. The development of "intelligent" agents with molecular logic capabilities are of great hope, but their full theranostic potential has yet to be realized. The original concept of nanoagents based on "Biocomputing based on particle disassembly" technology has been extended to nucleic acids (NAs) interfaces and inputs. By exploiting the unique properties of NAs, we designed nanostructures that can implement all basic single- and dual-input logic gates on a unified nanoparticle platform through DNA strand displacement triggered by oligonucleotide inputs. Performance of nanostructures was investigated across various output signal detection formats including specific interaction with nanosized objects and targeting cells. Here, we demonstrate autonomous theranostic biocomputing agents based on nanoparticles and DNA interfaces ("DNA-transformers") capable of executing a functionally complete set of Boolean logic gates (YES, NOT, AND, and OR) within a single all-in-one particle structure. Each DNA-transformer is constructed through a multi-layered self-assembly of nanoparticles via DNA-interfaces. The route of the agent's disassembly induced by the particular combination of the specific ssDNA inputs determines the agents' ability to produce the programmed outputs compatible with theranostic applications such as specific targeting of HER2/neu-positive cancer cells. The developed all-in-one DNA-based nanoagents represent a significant advancement in molecular logic devices, establishing a versatile platform for smart nanoagents equally suitable for diagnostic and therapeutic applications.

摘要

病原体侵入宿主生物体的多样性凸显了对同样复杂的预防机制的需求。具有分子逻辑能力的“智能”试剂的开发前景广阔,但其完整的治疗诊断潜力尚未实现。基于“基于颗粒拆解的生物计算”技术的纳米试剂的最初概念已扩展到核酸(NA)界面和输入。通过利用核酸的独特性质,我们设计了纳米结构,该结构可以通过寡核苷酸输入触发的DNA链置换在统一的纳米颗粒平台上实现所有基本的单输入和双输入逻辑门。通过各种输出信号检测形式研究了纳米结构的性能,包括与纳米尺寸物体和靶向细胞的特异性相互作用。在这里,我们展示了基于纳米颗粒和DNA界面的自主治疗诊断生物计算试剂(“DNA变压器”),其能够在单个一体化颗粒结构内执行一组功能完整的布尔逻辑门(是、非、与和或)。每个DNA变压器通过纳米颗粒经由DNA界面的多层自组装构建而成。由特定单链DNA输入的特定组合诱导的试剂拆解途径决定了试剂产生与治疗诊断应用(如HER2/neu阳性癌细胞的特异性靶向)兼容的编程输出的能力。所开发的基于DNA的一体化纳米试剂代表了分子逻辑器件的重大进展,为同样适用于诊断和治疗应用的智能纳米试剂建立了一个通用平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/744d/12374668/de9546c1b614/thnov15p8451g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索