A Mitochondria-Targeted Cryptocyanine-Based Photothermogenic Photosensitizer

Abstract

Cryptocyanine-based probes exhibit highly efficient photothermal conversion and represent a new class of photothermal agents for use in photothermal therapy (PTT). With the thermal susceptibility of mitochondria in mind, we have prepared a mitochondria-targeted, NIR-absorbing cryptocyanine probe (Mito-CCy) and evaluated its photophysical properties, photothermal conversion efficiency, biological compatibility, cytotoxicity, and mitochondrial localization in HeLa cells. Upon subjecting 0.5 mL of a PBS buffer solution (10 mM, pH 7.4, containing 50% DMSO) of Mito-CCy (0.5 mM) to 730 nm laser irradiation at 2.3 W/cm2, the temperature of the solution increased by 13.5 °C within 5 min. In contrast, the corresponding cryptocyanine (CCy) lacking the triarylphosphonium group gave rise to only an ∼3.4 °C increase in solution temperature under otherwise identical conditions. Mito-CCy also exhibited high cytotoxicity in HeLa cells when subject to photoirradiation. This light-induced cytotoxicity is attributed to the endogenous production of reactive oxygen species (ROS) induced under conditions of local heating. ROS are known to interfere with the mitochondrial defense system and to trigger apoptosis. By targeting the mitochondria, the present sensitizer-based photothermogenic approach is rendered more effective. As such, the system reported here represents the vanguard of what might be a new generation of organelle-targeted photothermal therapeutics.

Boron Dipyrromethene Nano‐Photosensitizers for Anticancer Phototherapies

“…Compared with PDT, PTT has emerged as a potentially safe option because the off‐target sensitizing effects and irreversible oxidative damage by ROS are frequently observed during PDT . Furthermore, most PDT agents are oxygen dependent and are ineffective in tumors with hypoxic environments . On the other hand, photothermal agents normally require a high light density to generate heat, which may damage normal tissues during therapy .…”

“…Furthermore, most PDT agents are oxygen dependent and are ineffective in tumors with hypoxic environments . On the other hand, photothermal agents normally require a high light density to generate heat, which may damage normal tissues during therapy . Nevertheless, employing PTT alone may be inefficient for complete tumor ablation, and the remaining tumor cells can rapidly develop heat resistance, leading to the failure of PTT to cure cancer .…”

“…PTT is also a commonly used type of phototherapy for cancer treatment . Typically, PSs generate heat through nonradiative relaxation pathways from excited states to the ground state by absorbing photons produced by light irradiation, eventually leading to cancer cell death . Additionally, PTT requires PSs that exhibit low fluorescence and 1 O 2 quantum yield to ensure a high nonradiative relaxation probability …”

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

“…18,19 (iii) Imaging-guided PTT is facilitated by fluorescence imaging, magnetic resonance imaging, CT imaging, or photoacoustic imaging with theranostic nanoparticles. 26,27 The nuclear-targeting nanoparticles synthesized by Pan et al can exert PTT under an extremely low NIR laser of 0.2 W/cm 2 to destroy the nuclear DNA, inhibit the DNA repair process and triggering the apoptosis of tumor cells. 22 Advances in nanotechnology have led to continuous changes in its development, such as the transition of photothermal conversion nanomaterials from inorganic to organic, the shift from single PTT effect to multifunctional theranostics and the change in focus from sole heat production efficiency to placing equal emphasis on biosafety and efficacy.…”

A Dual‐Targeted Organic Photothermal Agent for Enhanced Photothermal Therapy

“…Much effort has gone into the development of efficient SOPs,a nd some SOPs exhibited good photothermal therapeutic outcomes. [17][18][19][20] However,t ot he best of our knowledge,most of the reported methods for cancer were based on passive targeting through intratumoral or intravenous injection. Inspired by the active-targeting delivery strategy, as pecific and efficient method for killing cancer cells in vivo, [21][22][23][24] we proposed an active tumor-a nd organelletargeted theranostic (ATOT) strategy for designing SOPs, which were named ATOT-SOPs,t or ealize the goal of selectively and efficiently killing cancer cells and minimizing damage to normal tissue (Scheme 1).…”