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It addressed the major challenges in drug delivery systems, i.e., monitoring real-time drug release, targeted, and on-demand drug delivery. To monitor real-time drug release, the fluorescence quenching of the cancer drug, doxorubicin (DOX), by in situ synthesized gold nanoparticles (AuNPs) through the Nanomaterial Surface Energy Transfer (NSET) mechanism was explored. Photoisomerization and size switching were characterized using UV\u2013vis spectroscopy and dynamic light scattering (DLS) techniques. The NSET process during in situ synthesis of AuNPs and drug release from nanocarrier after 365 nm UV light exposure was demonstrated by steady-state and time-resolved fluorescence of DOX. The mPEG-PLA-Spiropyran-DOX (3:1:1) formulation exhibited \u223c 73.16% encapsulation efficiency and \u223c 6.45% DOX-loading with proven kinetic stability. Sustained DOX release over 50 h was validated through in vitro studies at pH 5.5, 6.5, and 7.4, showing enhanced DOX release at acidic pH 5.5, representative of cancer cell organelles with prolonged UV exposure. Cell internalization, intracellular phototriggered drug release, and fluorescence cell imaging in mouse breast adenocarcinoma cells (4T1) were investigated. The results demonstrated that the micellar nanocarrier, after 365 nm UV light exposure, was highly efficient in inducing apoptosis, significant cytotoxicity, and mitochondrial membrane depolarization. Furthermore, in vivo studies were conducted in both oral and breast cancer-bearing mice to assess tumor growth inhibition, changes in body weight, tumor weight, and immunohistochemical analysis. Notably, the therapeutic response was more pronounced in oral cancer, allowing for enhanced UV penetration and efficient activation of the micellar system. Overall, this study highlighted the potential of the dual-responsive micellar drug delivery system for targeted, on-demand cancer therapy with real-time monitoring. The enhanced efficacy in treating superficial malignancies underscores its promise for future clinical applications.<\/jats:p>","DOI":"10.1021\/acsabm.5c00770","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T17:21:27Z","timestamp":1760635287000},"page":"9680-9695","source":"Crossref","is-referenced-by-count":5,"title":["Targeted Phototriggered and pH-Responsive Micellar\nCancer Drug Delivery System with Real-Time Monitoring through the\nNSET Mechanism"],"prefix":"10.1021","volume":"8","author":[{"given":"Shalini","family":"Dyagala","sequence":"first","affiliation":[{"name":"Birla Institute of Technology and Science , , Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District , , ,","place":["Hyderabad, Telangana, India, 500078"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Paul","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science , , Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District , , ,","place":["Hyderabad, Telangana, India, 500078"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha","family":"Das","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science , , Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District , , ,","place":["Hyderabad, Telangana, India, 500078"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayantan","family":"Halder","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science , , Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District , , ,","place":["Hyderabad, Telangana, India, 500078"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1575-4206","authenticated-orcid":true,"given":"Swati","family":"Biswas","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science , , Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District , , ,","place":["Hyderabad, Telangana, India, 500078"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8278-2912","authenticated-orcid":true,"given":"Subit K.","family":"Saha","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science , , Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District , , ,","place":["Hyderabad, Telangana, India, 500078"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"2026072914070223900_cit1","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1021\/nn9018587","article-title":"Stimuli-Responsive Liposome Fusion\nMediated by Gold Nanoparticles","volume":"4","author":"Pornpattananangkul","year":"2010","journal-title":"ACS Nano"},{"key":"2026072914070223900_cit2","doi-asserted-by":"publisher","first-page":"467","DOI":"10.2147\/IJN.S36654","article-title":"Targeted Therapy\nUsing Nanotechnology:\nFocus on Cancer","author":"Sechi","year":"2014","journal-title":"IJN"},{"key":"2026072914070223900_cit3","doi-asserted-by":"publisher","first-page":"7554","DOI":"10.1021\/am5009002","article-title":"Spiropyran-Modified Gold Nanoparticles: Reversible Size Control of\nAggregates by UV and Visible Light Irradiations","volume":"6","author":"Shiraishi","year":"2014","journal-title":"ACS Appl. 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