eprintid: 10129248 rev_number: 14 eprint_status: archive userid: 608 dir: disk0/10/12/92/48 datestamp: 2021-06-07 16:21:27 lastmod: 2021-10-15 23:02:22 status_changed: 2021-06-07 16:21:27 type: article metadata_visibility: show creators_name: Kim, N creators_name: Kim, E creators_name: Kim, H creators_name: Thomas, MR creators_name: Najer, A creators_name: Stevens, MM title: Tumor-Targeting Cholesterol-Decorated DNA Nanoflowers for Intracellular Ratiometric Aptasensing ispublished: pub divisions: UCL divisions: B04 divisions: C06 divisions: F64 note: © 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. abstract: Probing endogenous molecular profiles is of fundamental importance to understand cellular function and processes. Despite the promise of programmable nucleic-acid-based aptasensors across the breadth of biomolecular detection, target-responsive aptasensors enabling intracellular detection are as of yet infrequently realized. Several challenges remain, including the difficulties in quantification/normalization of quencher-based intensiometric signals, stability issues of the probe architecture, and complex sensor operations often necessitating extensive structural modeling. Here, the biomimetic crystallization-empowered self-assembly of a tumor-targetable DNA–inorganic hybrid nanocomposite aptasensor is presented, which enables Förster resonance energy transfer (FRET)-based quantitative interpretation of changes in the cellular target abundance. Leveraging the design programmability and high-throughput fabrication of rolling circle amplification-driven DNA nanoarchitecture, this designer platform offers a method to self-assemble a robust nanosensor from a multifunctionality-encoded template that includes a cell-targeting aptamer, a ratiometric aptasensor, and a cholesterol-decorating element. Taking prostate cancer cells and intracellular adenosine triphosphate molecules as a model system, a synergistic effect in the targeted delivery by cholesterol and aptamers, and the feasibility of quantitative intracellular aptasensing are demonstrated. It is envisioned that this approach provides a highly generalizable strategy across wide-ranging target systems toward a biologically deliverable nanosensor that enables quantitative monitoring of the abundance of endogenous biomolecules. date: 2021-03-18 date_type: published publisher: WILEY-V C H VERLAG GMBH official_url: https://doi.org/10.1002/adma.202007738 oa_status: green full_text_type: pub primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_id: 1846697 doi: 10.1002/adma.202007738 language_elements: English lyricists_name: Thomas, Michael lyricists_id: MTHOA12 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: ADVANCED MATERIALS volume: 33 number: 11 article_number: 2007738 pages: 10 issn: 1521-4095 citation: Kim, N; Kim, E; Kim, H; Thomas, MR; Najer, A; Stevens, MM; (2021) Tumor-Targeting Cholesterol-Decorated DNA Nanoflowers for Intracellular Ratiometric Aptasensing. ADVANCED MATERIALS , 33 (11) , Article 2007738. 10.1002/adma.202007738 <https://doi.org/10.1002/adma.202007738>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10129248/1/adma.202007738.pdf