{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:30:27Z","timestamp":1778599827854,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chemotherapy using a nanoscaled drug delivery system is an effective cancer therapy, but its high drug concentration often causes drug resistance in cancer cells and normal cell damage. Combination therapy involving two or more different cell signaling pathways can be a powerful tool to overcome the limitations of chemotherapy. Herein, this article presents nanogel (NG)\u2010mediated co\u2010delivery of a chemodrug camptothecin (CPT) and mitochondria\u2010targeting monomer (MT monomer) for efficient activation of two modes of the programmed cell death pathway (apoptosis and necroptosis) and synergistic enhancement of cancer therapy. CPT and the monomer are incorporated together into the redox\u2010degradable polymeric NGs for release in response to the intracellular glutathione. The MT monomer is shown to undergo reactive oxygen species (ROS)\u2010triggered disulfide polymerization inside the cancerous mitochondria in cooperation with the chemotherapeutic CPT elevating the intracellular ROS level. The CPT\/monomer interconnection in cell death mechanisms for mitochondrial dysfunction and enhanced cell death is evidenced by a series of cell analyses showing ROS generation, mitochondria damage, impacts on (non)cancerous or drug\u2010resistant cells, and cell death modes. The presented work provides beneficial insights for utilizing combination therapy to facilitate a desired cell death mechanism and developing a novel nanosystem for more efficacious cancer treatment.<\/jats:p>","DOI":"10.1002\/smll.202308872","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T16:02:38Z","timestamp":1700755358000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Drug\u2010Loaded Nanogel for Efficient Orchestration of Cell Death Pathways by Intramitochondrial Disulfide Polymerization"],"prefix":"10.1002","volume":"20","author":[{"given":"Eun Seong","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Chemistry Ulsan National Institute of Science and Technology (UNIST)  Ulsan 44919 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangpil","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry Ulsan National Institute of Science and Technology (UNIST)  Ulsan 44919 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dohyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry Ulsan National Institute of Science and Technology (UNIST)  Ulsan 44919 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2437-5232","authenticated-orcid":false,"given":"Eunshil","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Chemistry Ulsan National Institute of Science and Technology (UNIST)  Ulsan 44919 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0252-0985","authenticated-orcid":false,"given":"Ja\u2010Hyoung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Ulsan National Institute of Science and Technology (UNIST)  Ulsan 44919 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-017-0004-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2007.387"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/185117a0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtchem.2018.02.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.02.002"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijch.201900160"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.1c13634"},{"key":"e_1_2_8_9_1","volume-title":"ACS Symposium Series","author":"Ratner B. 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