Multifunctional Conjugated Polymeric Nanomaterials for Real-Time Biosensing and Phototheranostics of Bacterial Infection
Implementing Organization
Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR)
Principal Investigator
Dr. Moirangthem Anita Chanu
Jawaharlal Nehru Centre For Advanced Scientific Research (Jncasr), Bengaluru
manitachanu@gmail.com
Project Overview
The rapid emergence of antibiotic-resistant bacteria in recent years poses a significant global concern due to the failure of antibiotic treatment in various infections caused by different bacterial strains.¹ To solve this alarming situation, it is urgent to develop a simple, cost-effective and efficient strategy for simultaneous detection and therapy beyond conventional antibiotic based pharmacology.
Phototheranostics offers a promising antimicrobial strategy due to its non-invasiveness, spatial-temporal precision, and potent bactericidal ability.² The selective detection of bacteria through differential binding to bacterial membranes³ combined with phototherapies viz photo thermal therapy (PTT) and photodynamic therapy (PDT) has gathered significant attention from researchers worldwide.⁴-⁵ In PDT, a light-activatable photosensitizer generates reactive oxygen species (ROS) upon irradiation with a specific wavelength, leading to oxidative damage and bacterial eradication. Whereas, PTT employs a photothermal agent that converts light energy into heat, inducing localized hyperthermia to kill bacteria. The integration of both therapies represents a powerful approach for the effective treatment of bacterial infections.
Various materials have been reported for bacterial detection,⁶ differentiations,⁷ phototherapies (PDT and PTT). However, there is limited literature on conjugated polymer nanomaterials (CPNs) for sensing-guided synergistic PDT and PTT, which enable dual-mode early pathogen detection and simultaneous phototherapeutic treatment. Several studies have demonstrated that polyfluorene-based conjugated polymers can generate ROS under light irradiation, making them effective for PDT⁸-¹⁰, but PTT remains less explored. This can be addressed by incorporating molecular rotors that dissipate excited-state energy as heat.
The proposal aims to rationally design polyfluorene-based conjugated polymers by incorporating various acceptor units into the polymer backbone to enhance reactive oxygen species (ROS) generation and photothermal heat conversion, through modulation of intersystem crossing and non-radiative decay pathways. Herein, enhanced electron-accepting ability induces a red shift in the polymer’s excitation and emission wavelengths, which facilitates deeper tissue penetration with low photodamage, while also increasing triplet exiton generation for improved PDT efficacy. Additionally, the incorporation of a rotor moiety acts as a molecular rotor to promote efficient heat release for PTT. The motivation comes from my PhD work where I synthesized a polyfluorene-thiophine based copolymer, which demonstrated good antibacterial activity against bacteria via membrane disruption while exhibiting low cytotoxicity towards HEK 293 cell lines.¹¹ It also tries to address the key challenges of real-time pathogen detection and clinical translation such as biocompatibility, applicability at various physiological conditions and complex bio-systems etc.
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