Research Projects

Rationale of Research: Photothermal therapy (PTT) is a highly effective and non-invasive treatment modality for cancer. PTT employs photothermal (PT) agents, which can be either organic or inorganic materials that kill cancer cells by raising the local temperature of tissues. This heating occurs due to the release of energy during the relaxation of the photoexcited state via non-radiative decay. Near-infrared (NIR) absorbing dyes, particularly those in the NIR-III region (1500–2500 nm), are especially advantageous because NIR-III light photons can penetrate deeper into tissues with fewer detrimental effects compared to ultraviolet and visible light, owing to their lower energy. Thus, this proposal aims to synthesize NIR-III absorbing dyes by constructing narrow band-gap metalla-carbaporphyrinoid structures. Unlike traditional strategies for lowering the optical gap of organic dyes, our design strategy relies on unique dπ–pπ orbital mixing between a late transition metal ion (Pt) and the π-orbitals of the ligand backbone. Specifically, we propose the synthesis of unique Pt(II)-carbaporphyrinoid macrocycles as NIR-III dyes, which will be further transformed into zwitterions to enhance their bioavailability by improving water solubility.Objective: The principal objectives of this research proposal are: (a) to develop the first generation of NIR-III absorbing metalla-carbaporphyrinoid macrocycles, (b) to achieve superior photothermal conversion efficiency (η), and (c) to improve their bioavailability by converting them into a zwitterionic form.Experiments: This research involves several work packages (WPs): WP1: Design, synthesis, and chemical characterization of NIR-III absorbing carbaporphyrinoid dyes. WP2: Computational modeling of these dyes to understand their electronic structure using DFT. WP3: Comprehensive photophysical and electrochemical characterization of the dyes to assess their suitability as PT agents for PTT. WP4: Investigation of the in-vitro PT conversion efficiency and photostability of the NIR-III dyes. At a later stage of the project, based on the in-vitro findings, the therapeutic efficacy of these dyes for PTT will be evaluated in collaboration with experts in in-vivo experimentation. Significance: While various NIR-I and NIR-II (700–1500 nm) dyes have been explored for PTT, transitioning to the NIR-III region offers significant advantages for deep tissue treatment—a persistent challenge in PTT due to the lack of advanced materials capable of absorbing in this region. Additionally, organic dyes present advantages over inorganic nanoparticles and polymer-based PT agents, which often suffer from toxicity and accumulation issues. Therefore, the development of NIR-III absorbing organic dyes as efficient PT agents for PTT represents a significant advancement in the field.