Rationale Design of a Liposomal Formulated Phenanthro[9, 10-d]imidazole-Based ZnII Complex as a Targeted Anticancer Unit

Mallayasamy Siva; Anushree Lye; Debojit Talukdar; Nanjundan Raghul; Atanu Barik; Adele Stewart; Gaurav Das; Biswanath Maity; Priyadip Das

doi:10.1021/acsabm.6c01217

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Rationale Design of a Liposomal Formulated Phenanthro[9, 10-d]imidazole-Based ZnII Complex as a Targeted Anticancer Unit

Journal article

Peer reviewed

Rationale Design of a Liposomal Formulated Phenanthro[9, 10-d]imidazole-Based ZnII Complex as a Targeted Anticancer Unit

Mallayasamy Siva, Anushree Lye, Debojit Talukdar, Nanjundan Raghul, Atanu Barik, Adele Stewart, Gaurav Das, Biswanath Maity and Priyadip Das

ACS applied bio materials

10/06/2026

DOI: 10.1021/acsabm.6c01217

PMID: 42838528

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Abstract

The development of targeted and multifunctional anticancer nanoplatforms remains challenging due to limited selectivity, systemic toxicity, drug resistance, and off-target effects associated with conventional platinum-based chemotherapy. 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 μg mL-1 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.

Schiff base

folate receptor

cancer nanotherapy

drug delivery

liposomes

Details

Title: Subtitle: Rationale Design of a Liposomal Formulated Phenanthro[9, 10-d]imidazole-Based ZnII Complex as a Targeted Anticancer Unit
Creators: Mallayasamy Siva - Sengunthar Engineering College (Autonomous)
Anushree Lye - Department of Biological Sciences
Debojit Talukdar - Chittaranjan National Cancer Institute
Nanjundan Raghul - SRM Institute of Science and Technology
Atanu Barik - Bhabha Atomic Research Centre
Adele Stewart - University of Iowa
Gaurav Das - Chittaranjan National Cancer Institute
Biswanath Maity - Department of Biological Sciences
Priyadip Das - SRM Institute of Science and Technology
Resource Type: Journal article
Publication Details: ACS applied bio materials
DOI: 10.1021/acsabm.6c01217
PMID: 42838528
NLM abbreviation: ACS Appl Bio Mater
ISSN: 2576-6422
eISSN: 2576-6422
Publisher: American Chemical Society
Grant note: 58/14/14/2021-BRNS/37219 / Board of Research in Nuclear Sciences 5/4/1- 22/CVD/2022-NCD-I / Indian Council of Medical Research
Language: English
Electronic publication date: 10/06/2026
Academic Unit: Neuroscience and Pharmacology
Record Identifier: 9985243569502771

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