Ultra‐Small Nano‐Assemblies as Tumor‐Targeted and Renal Clearable Theranostic Agent for Photodynamic Therapy

Abstract

It is a challenge to design photosensitizers to balance between the tumor‐targeting enrichment for precise treatment and efficient clearance within a reasonable timescale for reducing side effects. Herein, an ultra‐small nano‐photosensitizer 1a with excellent tumor‐specific accumulation and renal clearance is reported. It is formed from the self‐assembly of compound 1 bearing three triethylene glycol (TEG) arms and two pyridinium groups in water. The positively charged surface with neutral TEG coating enables 1a to efficiently target the tumor, with the signal‐to‐background ratio reaching as high as 11.5 after tail intravenous injection. The ultra‐small size of 1a with an average diameter of 5.6 nm allows its fast clearance through kidney. Self‐assembly also endows 1a with an 18.2‐fold enhancement of reactive oxygygen species generation rate compared to compound 1 in organic solution. Nano‐PS 1a manifests an excellent photodynamic therapy efficacy on tumor‐bearing mouse models. This work provides a promising design strategy of photosensitizers with renal clearable and tumor‐targeting ability.

Development of organic photosensitizers for antimicrobial photodynamic therapy

“…123 Finally, systemic toxicity risk is a significant concern when applying photosensitizers to treat in vivo infections. 113,114 Despite these challenges, aPDT has shown promising preliminary results, and with further exploration and optimization, it is expected to play a more significant role in the clinical treatment of bacterial infections.…”

“…To address this challenge, Yang's group engineered a nanophotosensitizer featuring three hydrophilic triethylene glycol arms and two cationic pyridinium groups in an aqueous medium. 113 Notably, the nanophotosensitizer exhibited an ultra-small size, with an average diameter of 5.6 nm, facilitating its clearance via urinary excretion with reduced nonspecific accumulation. To further enhance the post-operative safety of aPDT, Liu's group designed a series of self-degradable D–A photosensitizers.…”

Regulating Photosensitizer Metabolism with DNAzyme-Loaded Nanoparticles for Amplified Mitochondria-Targeting Photodynamic Immunotherapy

“…Photodynamic therapy (PDT) is emerging as an attractive modality for cancer therapy owing to the high spatiotemporal selectivity, minimal invasiveness, and low systemic toxicity. − Mitochondria are highly sensitive to reactive oxygen species (ROS), and the mitochondrial apoptosis pathway plays an important role in most antitumor mechanisms. − Particularly, accumulating evidence has demonstrated that mitochondria-targeting PDT can activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway-based innate immunity by inducing mitochondrial DNA (mtDNA) damage and release. mtDNA contains inflammatory non-methylated CpG sequences, which is similar to bacterial DNA that can activate the cGAS-STING pathway. − Thus, efficient mitochondria-specific photosensitizer (PSs) accumulation is highly recommended to improve PDT and PDT-triggered innate immunity.…”

Engineering of a GSH activatable photosensitizer for enhanced photodynamic therapy through disrupting redox homeostasis

“…[1][2][3][4][5] ROS (e.g., anion superoxide, hydroxyl radical and singlet oxygen) are usually generated by intracellular oxidoreductase-catalyzed processes and exogenous light stimulation. [6][7][8][9] The elevated ROS could promote the proliferation of tumors, whereas an excessive amount of ROS would elicit cell death due to strengthened oxidative stress. 10,11 To equilibrate the high-level of oxidative stress, cancer cells would functionally enhance the endogenous antioxidant systems by producing glutathione (GSH), an important reducing agent enriched in tumor tissue.…”