A near infrared light activated phenothiazine based cancer cell specific phototherapeutic system: a synergistic approach to chemo-photothermal therapy†

Abstract

In the pursuit of more effective cancer therapies, phototherapy has emerged as a promising approach due to its non-invasive nature and high precision. This study presents the development of a near-infrared (NIR) light-responsive phenothiazine (PTZ) based phototherapeutic system designed for targeted cancer treatment. This phototherapeutic system integrates four crucial elements for enhanced therapeutic efficacy: cancer cell-specific activity, mitochondrial targeting, photothermal conversion, and controlled drug release. The PTZ system utilizes the acidochromic 1,3-oxazine ring, which opens in the acidic tumor microenvironment, forming a positive iminium ion (CN⁺). This ionic species targets cancer cell mitochondria, ensuring precise localization. Under NIR light irradiation (640 nm), the phototherapeutic system undergoes a red shift in the absorption and reduction in the fluorescence intensity, demonstrating a significant photothermal effect that converts light to heat, thereby inducing tumor cell apoptosis. Furthermore, NIR light triggers the controlled release of the anticancer drug chlorambucil, enabling precise spatiotemporal drug delivery. The closed form of the phototherapeutic system also facilitates drug release upon visible light irradiation (≥410 nm) with high photochemical efficiency. This dual-mode photothermal and photocontrolled drug delivery offers a synergistic approach to cancer therapy, maximizing therapeutic outcomes while minimizing side effects. Our findings underscore the potential of this innovative phototherapeutic system to advance cancer treatment through targeted, controlled, and effective drug delivery.