Singlet Oxygen Generation in Dark‐Hypoxia by Catalytic Microenvironment‐Tailored Nanoreactors for NIR‐II Fluorescence‐Monitored Chemodynamic Therapy

Abstract

Singlet oxygen (1O2) has a potent anticancer effect, but photosensitized generation of 1O2 is inhibited by tumor hypoxia and limited light penetration depth. Despite the potential of chemodynamic therapy (CDT) to circumvent these issues by exploration of 1O2‐producing catalysts, engineering efficient CDT agents is still a formidable challenge since most catalysts require specific pH to function and become inactivated upon chelation by glutathione (GSH). Herein, we present a catalytic microenvironment‐tailored nanoreactor (CMTN), constructed by encapsulating MoO42− catalyst and alkaline sodium carbonate within liposomes, which offers a favorable pH condition for MoO42−‐catalyzed generation of 1O2 from H2O2 and protects MoO42− from GSH chelation owing to the impermeability of liposomal lipid membrane to ions and GSH. H2O2 and 1O2 can freely cross the liposomal membrane, allowing CMTN with a built‐in NIR‐II ratiometric fluorescent 1O2 sensor to achieve monitored tumor CDT.

Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy

“…However, the most convenient and efficient way to generate this species is through the photosensitized excitation of ambient triplet oxygen. Only a few metal-based nanomaterials consisting of Mo [59,76] and Mn [77] active centers have the capability to generate 1 O 2 without the need for light irradiation. For example, Song et al have developed a high-efficiency chemodynamic and chemiluminescenct system comprising ultrathin MnO x nanosheet and semiconducting polymer nanoparticles.…”

“…However, the most convenient and efficient way to generate this species is through the photosensitized excitation of ambient triplet oxygen. Only a few metal‐based nanomaterials consisting of Mo [ 59 , 76 ] and Mn [ 77 ] active centers have the capability to generate 1 O 2 without the need for light irradiation. For example, Song et al.…”

Recent advances of cancer chemodynamic therapy based on Fenton/Fenton-like chemistry

“…14d ). 69 CMTN could not only provide a favorable pH range for MoO 4 2− induced generation of ROS but also protect MoO 4 2− from being removed by GSH because of the impermeability of liposomal lipid membrane to GSH. This work provides a new concept of “protection” instead of “depletion”, which may point out a new insight for designing antioxidant agents based on the concept of protection.…”

De Novo Synthesis of Acridone-Based Zn-Metal–Organic Framework (Zn-MOF) as a Photocatalyst: Application for Visible Light-Mediated Oxidation of Sulfides and Enaminones

“…Singlet oxygen ( 1 O 2 ), generated by activation of the ground-state triplet oxygen ( 3 O 2 ) by energy transfer from triplet-excited photosensitizers, is one of the most important reactive oxygen species (ROS). − It continues to be exploited in several applications, including photodynamic therapy, , wastewater treatment, , degradation of organic pollutants, , and diverse organic transformations. − As a mild, green, and inexpensive oxidant, 1 O 2 has gained much attention in organic photocatalysis. − The generation of 1 O 2 by photosensitization can be accomplished in a homogeneous medium by employing several organic photosensitizers − and in a heterogeneous phase by immobilizing the photosensitizers on solid supports. , Advantages with the latter approach include: (i) enhancement of photostability, (ii) efficient generation of 1 O 2 by obviating self-quenching through triplet–triplet annihilation, (iii) ease of separation of oxygenated products, and (iv) recyclability of the sensitizer. Among various systems known for the generation of 1 O 2 in a heterogeneous phase, porous materials such as metal–organic frameworks (MOFs), − covalent-organic frameworks (COFs) − and porous organic polymers (POPs) − have emerged as inextricable materials in recent times.…”