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Mertansine (DM1), a potent cytotoxic agent with poor selectivity, dose-limiting toxicity, and a narrow therapeutic window, demands targeted delivery and precise concentration regulation for safety and efficacy. Herein, we constructed two Janus DNA triangular prism-based molecular buffers (3A-JTP-3S2 and A-MTP-3S2) for targeted DM1 delivery and concentration regulation. Both of the buffers integrate nucleolin-targeting aptamer (Apt-AS1411) for cancer cell recognition and DM1-specific aptamer (Apt-Seq2-X) for regulating DM1 concentration within a desired therapeutic range. When we evaluated their endocytic behaviors, 3A-JTP-3S2 was prone to lysosomal degradation via clathrin-mediated endocytosis. In contrast, A-MTP-3S2, a higher-order multivalent assembly built from 3A-JTP-3S2 units, forms an endocytosis-resistant DNA network that anchors onto cell membranes due to its enlarged size. We thus prioritized the latter for subsequent studies. A-MTP-3S2 delivered DM1 with favorable tumor-targeting ability across a total DM1 concentration (CDM1) range of 50\u20131000 nM, significantly killing A549 cancer cells (viability: 55.7 \u00b1 8.15% \u2212 50.84 \u00b1 2.27%) while showing less impact on BEAS-2B normal cells (viability: 91.21 \u00b1 2.72% \u2212 76.31 \u00b1 5.97%). Notably, even as CDM1 varied from 50 to 1000 nM, A-MTP-3S2 still maintained free DM1 at a relatively constant level (1\u201355 nM), confirming its great buffering capacity. Our work offers a facile strategy for simultaneous targeted delivery and precise concentration regulation of low-specific and high-toxic drugs.<\/jats:p>","DOI":"10.1021\/acsabm.6c00958","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:01:15Z","timestamp":1789023675000},"page":"8593-8606","source":"Crossref","is-referenced-by-count":0,"title":["Aptamer-Functionalized DNA Frameworks as Targeted Drug Buffers for Concentration Regulation of Maytansine"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4424-4814","authenticated-orcid":true,"given":"Dan","family":"Jiang","sequence":"first","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xiong","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Luan","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Luo","sequence":"additional","affiliation":[{"name":"Changsha Normal University , , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7337-0999","authenticated-orcid":true,"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2890-682X","authenticated-orcid":true,"given":"Jin","family":"Huang","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8122-7140","authenticated-orcid":true,"given":"Xiaohai","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9390-4938","authenticated-orcid":true,"given":"Kemin","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"2026092100085414000_cit1","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41568-025-00801-2","article-title":"Cancer Treatments Accelerate Ageing","volume":"25","author":"Demaria","year":"2025","journal-title":"Nat. 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