Abhijit De

Mitochondrial metabolism plays a crucial role in cancer progression and is associated with effective channeling of electrons through Complex I. The ability to adapt this electron flow as per cellular demands is critical for energy homeostasis. Our observations suggest that proliferating cells regulate the electron entry point through alterations in the levels of Methylation-Controlled J-protein (MCJ). Elevated MCJ levels were found to promote aggressive proliferative and migratory phenotypes, leading to increased primary tumor burden. The phenotype was attributed to MCJ-mediated regulation of mitochondrial bioenergetic plasticity, enabling a preferential rerouting of electron flux through succinate dehydrogenase complex (Complex II). Consequently, cells exhibited suppressed glycolysis and a metabolic shift toward lipid-fueled mitochondrial respiration, marked by increased lipid accumulation and its oxidation. Despite Complex I uncoupling, these cells maintained better respiratory output and preserved NADH levels to support an increased redox potential. These findings decouple the reliance on Complex I for effective mitochondrial respiration and underscore the significance of Complex II-driven metabolism in tumor growth, an important consideration for development of future therapeutics, particularly when current strategies predominantly target Complex I-dependent respiration.

*Corresponding Author: Abhijit De, PhD (ade@actrec.gov.in). ^#Presenting Author: Anuradha Gupta, (anuradha.gupta@actrec.gov.in) Keywords biomimetic nanoformulation photothermal agents homotypic interaction Background: Photothermal therapy (PTT) is an emerging cancer nanomedicine. Our group focuses on developing tumor-targeted theranostic photothermal agents (PTAs) using organic near-infrared fluorescent (NIRF) imaging-compatible FF-BSC- L, L-diphenylalanine-conjugated BF2-oxasmaragdyrin and IR820 dyes. Integrating biomimetic principles into PTAs facilitates enhanced homing through active nanomaterial uptake within tumors. We aim to design a biomimetic PTA nanomaterial that enables homotypic binding interactions for cancer theranostic applications. Materials and Methods: The synthesis of cancer cell ghost membranes (CCGMs) was optimized for EpCAM-overexpressing radioresistant breast cancer cells, with encapsulation of PTAs achieved via electroporation. Physical characterization of CCGMs was performed using dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta potential analysis to evaluate hydrodynamic size, morphology, and surface charge, respectively. Immunoblotting confirmed cancer cell-specific markers on CCGM-NIR dye nanoconjugates, and in vitro efficacy was assessed using the MTT assay. Results: The optimized CCGM protocol produced an enriched membrane fraction with retained membrane-anchored proteins (EpCAM, Cadherin) while depleting significant mitochondrial and cytoplasmic components. DLS and TEM analyses revealed a biconcave cup-shaped structure with a mean diameter of 120 ± 20 nm, while zeta potential measurements indicated a surface charge of –13.1 ± 3 mV. PTA uptake was assessed via fluorescence confocal microscopy, and in vitro PTT efficacy was evaluated using both EpCAM-positive and -negative cancer cells. Conclusion: The NIRF PTA dye-encapsulated biomimetic nanoformulation enables active tumor targeting via homotypic binding to the EpCAM moiety on cell surfaces, potentially broadening the application of PTT therapy for deep-seated tumors. Article published online: 15 December 2025 © 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

*Corresponding Author: Dr. Abhijit De, PhD (ade@actrec.gov.in). ^#Presenting Author: Shaonlee Ghosh (shaonleeghosh@gmail.com) Keywords drug resistance EZH2 feedback regulation HER2 STAT3 TRIM-ing Background: HER2 positive breast cancer (BC) accounts for 20 to 25% BC cases worldwide. The personalized treatment strategy has improved disease outcomes significantly but the clinical challenge of drug resistance continues. In this context of drug resistance, our study focuses on regulatory roles of downstream signaling molecules driven by HER family receptors. Materials and Methods: Trastuzumab (R.I.-80) and neratinib (R.I.-10) drug-resistant HER2+ve BC cell models were established. Immunoblot and immunofluorescence was performed to check differentially expressed proteins of HER2-STAT3 signaling axis. TRIM-ing of candidate proteins led us to the validation of preliminary observations. Bioinformatics analyses were performed to delineate the role of STAT3, driving HER2 drug resistance. Results: In resistant cell models, heregulin-β1 ligand-driven phospho-STAT3 activation and HER2 TRIM-ing-mediated p-ERK, p-Akt, and p-STAT3 inhibition suggested STAT3 as a downstream target of HER2-HER3 signaling axis. STAT3 TRIM-ing showed significant (p < 0.05) abrogation of upstream kinases, indicating STAT3-driven positive feedback loop. Bioinformatic analysis of STAT3 interaction network revealed enhancer of zeste homologue 2(EZH2) as a lead interactor, which was overexpressed and constitutively activated in resistant cell model. EZH2's relevance in HER2-STAT3 axis was verified by inhibiting Akt. Also, STAT3 binding motifs in EZH2 and HER2 promoter region suggested their transcriptional regulation by STAT3, imparting the positive feedback loop. Conclusion: Our results underscores STAT3-mediated HER family receptor regulation, where EZH2's significant role was also realized. Thereby, the study highlights a STAT3-driven positive feedback loop, impacting HER2 drug resistance. Article published online: 15 December 2025 © 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

Experimental cancer therapeutics are rapidly advancing, with novel approaches emerging to reduce global cancer burden. This review focuses on challenges hindering the clinical integration of photothermal therapy (PTT), despite its therapeutic potential. Key PTT considerations include photothermal agent (PTA), laser properties and strategies for better application, efficacy and precision. Common parameters for PTA evaluation demonstrate biocompatibility, biodistribution and efficacy assessments. However, for clinical emphasis, targeting efficiency and post-therapy fate determination of PTA, sophisticated engineering of photonic devices, precision assessments as well as pain mitigation are critical. Directed future endeavours, keeping these insights, may facilitate application of PTT as a viable cancer treatment in clinical settings.

Multimodal imaging-guided evaluation of novel Au-SLN-mediated photothermal application showed precisive elimination of primary tumour mass in an orthotopic breast murine model, significantly enhancing life expectancy.

Psoriasis is a recurring autoimmune-driven inflammatory skin disorder characterised by red, scaly, dry skin patches, keratinocyte hyperproliferation and infiltration of inflammatory cells, impacting millions globally. Patients with psoriasis often require repeated treatments with corticosteroids, which are often associated with significant side effects and comorbidities. Therefore, there is a growing need for advanced nanomedicine-based therapeutic approaches. Resveratrol (RSV), a plant-derived polyphenol, has shown promising anti-inflammatory and antioxidant properties for the treatment and management of psoriasis. However, its therapeutic potential is limited due to its poor solubility, low stability, and reduced skin penetration. To overcome these challenges, we have developed dual-carrier conjugated nanoparticles (RSVNPL) composed of soya lecithin and poly(lactic-co-glycolic acid) (PLGA). To further enhance its ease of application and prolong skin residence time, RSVNPL was incorporated into a carbomer 974P-based hydrogel system, forming RSVNPGel. Our formulation demonstrated improved physicochemical properties, including enhanced spreadability, superior skin adhesiveness and stability. Ex vivo skin permeation studies confirmed a significantly higher accumulation of RSV in the epidermis and dermis compared to free drugs. In vivo, efficacy was investigated using imiquimod (IMQ)-induced psoriatic mouse model, where RSVNPGel treatment led to a notable reduction in epidermal thickness, inflammatory cell infiltration, and key histopathological features associated with psoriasis. Additionally, serum biochemical analysis and organ histology established the biocompatibility and safety of the formulation. Overall, RSVNPGel presents a promising nanocarrier-based strategy for the effective topical management of psoriasis, enhancing RSV delivery and therapeutic efficacy while minimizing systemic exposure. Research Highlights: Hybrid nanoparticles composite of soya lecithin and PLGA were developed for RSV delivery. The formulation enhanced skin penetration, retention and created a better skin adhesive profile in psoriatic lesions. Significant anti-psoriatic effects were achieved in a preclinical model. The system showed excellent safety and biocompatibility. Graphical