Cellular and Mitochondrial Dual‐Targeted Organic Dots with Aggregation‐Induced Emission Characteristics for Image‐Guided Photodynamic Therapy

Abstract

Targeted delivery of drugs toward mitochondria of specific cancer cells dramatically improves therapy efficiencies especially for photodynamic therapy (PDT), as reactive oxygen species (ROS) are short in lifetime and small in radius of action. Different from chemical modification, nanotechnology has been serving as a simple and nonchemical approach to deliver drugs to cells of interest or specific organelles, such as mitochondria, but there have been limited examples of dual-targeted delivery for both cells and mitochondria. Here, cellular and mitochondrial dual-targeted organic dots for image-guided PDT are reported based on a fluorogen with aggregation-induced emission (AIEgen) characteristics. The AIEgen possesses enhanced red fluorescence and efficient ROS production in aggregated states. The AIE dot surfaces are functionalized with folate and triphenylphosphine, which can selectively internalize into folate-receptor (FR) positive cancer cells, and subsequently accumulate at mitochondria. The direct ROS generation at mitochondria sites is found to depolarize mitochondrial membrane, affect cell migration, and lead to cell apoptosis and death with enhanced PDT effects as compared to ROS generated randomly in cytoplasm. This report demonstrates a simple and general nanocarrier approach for cellular and mitochondrial dual-targeted PDT, which opens new opportunities for dual-targeted delivery and therapy.

Unity Makes Strength: How Aggregation‐Induced Emission Luminogens Advance the Biomedical Field

“…C) Confocal images of MCF‐7 cancer cells (upper) and NIH‐3T3 cells (lower) after incubation with A14 dots (red, 20 µg mL −1 ) and MitoTracker Green (green, 200 × 10 −6 m ). Adapted with permission . Copyright 2015, Wiley‐VCH.…”

Nanoparticles-based photosensitizers with effect of aggregation-induced emission

“…The fluorescent probe systems DPBA-TPE with the AIE characteristics, which emit strong red fluorescence and can efficiently generate rOS in the state of aggregates are presented in [53]. DPBA-TPE in THF showed an absorption maximum at 480 nm and weak orange-red fluorescence with the emission maximum at 619 nm.…”

“…Schematic illustration of T-TTD NPs formation minutes, indicating the DPBA-TPE aggregates to be capable of efficient generation of the singlet oxygen species. Based on DPBA-TPE and the PEG derivatives with a folic acid (FA) fragment, the nano-sized dots with bright red fluorescence and high ROS generation were fabricated for cellular and mitochondrial dualtargeting [53]. To deliver AIE dots to mitochondria, the cationic TPP, which are able to accumulate in mitochondria in response to high mitochondrial membrane potential, reacted with the AIE dot suspension to yield FA-AIE-TPP dots.…”

The nanolight revolution is coming

“…AIE-dots have been used to stain various tissues, from blood vessels to cancer cells to intracellular organelles such as mitochondria. Last year, Liu, Tang and their colleagues reported an AIE-dot that could be useful in a type of light-activated treatment known as photodynamic therapy 5 . It carries two molecules on its surface: one to get the dot into a cancer cell, and another to make it stick to the mitochondria.…”