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Zn(II) complexes have emerged as promising low-toxicity metal-based alternatives, exhibiting enhanced cytotoxicity toward cancer cells compared to healthy cells. In this study, a Schiff base ligand (K) was synthesized via condensation of 4-(1H-phenanthro[9,10-d]imidazol-2-yl)aniline and salicylaldehyde followed by complexation with Zn(II) to form a Zn(II) complex (S1). To enhance site-specific cellular uptake, Zn(II) complex S1 was encapsulated within folic acid-functionalized 10,12-pentacosadiynoic acid (FA-PCDA) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based liposomes via molecular co-assembly, significantly improving stability and targeting capability. The resulting liposomal formulation of Zn(II) complex S1 (Lip-S1) exhibited characteristic fluorescence properties, enabling potential imaging applications. Lip-S1 selectively targeted folate receptor-expressing cervical cancer (HeLa) cells, demonstrating enhanced anticancer efficacy with a half maximal inhibitory concentration (IC50) of 143.8 \u03bcg mL\u20131 compared to free S1 and bare liposomes. Functional assays revealed that Lip-S1 inhibited cell proliferation, migration, and tumor spheroid growth while inducing apoptosis through mitochondrial membrane depolarization, elevated intracellular reactive oxygen species (ROS), caspase 3\/7 activation, and modulation of apoptotic proteins (Bax upregulation, Bcl-2 downregulation). ROS scavenging studies confirmed that apoptosis is primarily mediated by oxidative stress linked to the PI3K\/AKT (phosphatidylinositol 3 kinase\/protein kinase B) signaling pathway. Enhanced cellular internalization of Lip-S1 relative to controls was also observed. These results highlight Lip-S1 as a targeted, fluorescence-trackable nanoplatform for ROS-mediated anticancer therapy.<\/jats:p>","DOI":"10.1021\/acsabm.6c01217","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:01:26Z","timestamp":1791331286000},"page":"9701-9716","source":"Crossref","is-referenced-by-count":0,"title":["Rationale Design of a Liposomal Formulated Phenanthro[9, 10-d]imidazole-Based ZnII Complex as a Targeted Anticancer Unit"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-1076","authenticated-orcid":true,"given":"Mallayasamy","family":"Siva","sequence":"first","affiliation":[{"name":"SRM Institute of Science and Technology , , SRM Nagar, Potheri , , ,","place":["Kattankulathur, Tamil Nadu, India, 603203"]},{"name":"Erode Sengunthar Engineering College , , , ,","place":["Perundhurai, Erode, Tamil Nadu, India, 638057"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushree","family":"Lye","sequence":"additional","affiliation":[{"name":"Bose Institute, Unified Academic Campus , , EN80, Sector V, Bidhan Nagar , , ,","place":["Kolkata, West Bengal, India, 700091"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debojit","family":"Talukdar","sequence":"additional","affiliation":[{"name":"Chittaranajan National Cancer Institute 37 , , S.P. Mukherjee Road , ,","place":["Kolkata, India, 700 026"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanjundan","family":"Raghul","sequence":"additional","affiliation":[{"name":"SRM Institute of Science and Technology , , SRM Nagar, Potheri , , ,","place":["Kattankulathur, Tamil Nadu, India, 603203"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-843X","authenticated-orcid":true,"given":"Atanu","family":"Barik","sequence":"additional","affiliation":[{"name":"Bhabha Atomic Research Centre , , , ,","place":["Mumbai, Maharashtra, India, 400085"]},{"name":"Homi Bhabha National Institute , ,","place":["Mumbai, India, 400094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Stewart","sequence":"additional","affiliation":[{"name":"University of Iowa , , , ,","place":["Iowa City, Iowa, United States, 52242"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8432-5384","authenticated-orcid":true,"given":"Gaurav","family":"Das","sequence":"additional","affiliation":[{"name":"Chittaranajan National Cancer Institute 37 , , S.P. 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