Self-Reporting Molecular Prodrug for In Situ Quantitative Sensing of Drug Release by Ratiometric Photoacoustic Imaging.

Understanding the pharmacokinetics of prodrugs in vivo necessitates quantitative, noninvasive, and real-time monitoring of drug release, despite its difficulty. Ratiometric photoacoustic (PA) imaging, a promising deep tissue imaging technology with a unique capacity for self-calibration, can aid in solving this problem. Here, for the first time, a methylamino-substituted Aza-BODIPY (BDP-N) and the chemotherapeutic drug camptothecin (CPT) are joined via a disulfide chain to produce the molecular theranostic prodrug (BSC) for real-time tumor mapping and quantitative visualization of intratumoral drug release using ratiometric PA imaging. Intact BSC has an extremely low toxicity, with a maximum absorption at ∼720 nm; however, endogenous glutathione (GSH), which is overexpressed in tumors, will cleave the disulfide bond and liberate CPT (with full toxicity) and BDP-N. This is accompanied by a significant redshift in absorption at ∼800 nm, resulting in the PA800/PA720 ratio. In vitro, a linear relationship is successfully established between PA800/PA720 values and CPT release rates, and subsequent experiments demonstrate that this relationship can also be applied to the quantitative detection of intratumoral CPT release in vivo. Notably, the novel ratiometric strategy eliminates nonresponsive interference and amplifies the multiples of the signal response to significantly improve the imaging contrast and detection precision. Therefore, this research offers a viable alternative for the design of molecular theranostic agents for the clinical diagnosis and treatment of tumors.

Mitochondria-Targeting Boron Dipyrromethene Based Photosensitizers for Enhanced Photodynamic Therapy: Synthesis, Optical Properties, and in†vitro Biological Activity.

Increasing Investigations show that photosensitizers (PSs) which target mitochondria are useful for enhancing photodynamic therapy (PDT) efficacy. Herein, we carefully designed and synthesized four triphenylphosphonium (TPP)-modified boron dipyrromethene (BDP)-based PSs through Cu(I)-assisted "3+2" cycloaddition reaction. All of them exhibit intense red light absorption with maxima between 659 and 663 nm, considerable fluorescence emission with quantum yields of 0.16-0.23, high singlet oxygen generation efficiency ranging from 0.22 to 0.34, excellent mitochondria-targeting ability, and good biocompatibility. Upon illumination, they induce significant cancer cell death through a mitochondria-related apoptosis pathway. The IC50 values of these BDP dyes against MCF-7 cells were determined to be as low as 0.046-0.113 µM under rather low dosage of light irradiation (1.5 J ⋅ cm-2 ).

Singlet Oxygen-Responsive Polymeric Nanomedicine for Light-Controlled Drug Release and Image-Guided Photodynamic-Chemo Combination Therapy.

Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen (1O2)-sensitive aminoacrylate linkers into amphiphilic mPEG-b-PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an 1O2-responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NPBDP/PTX nanodrug could generate bright fluorescent signals and high levels of 1O2, which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NPBDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NPBDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.

Strategies for maximizing photothermal conversion efficiency based on organic dyes.

Photothermal therapy (PTT) has emerged as a promising therapeutic approach for tumor control and ablation. Attention has focused on exploring advanced organic photothermal agents (OPTAs), with advantages of easy modification, adjustable photophysical and photochemical properties, good compatibility, and inherent biodegradability. However, few detailed studies on how to maximally channelize nonradiative heat generation from the viewpoint of the photothermal conversion mechanism have been reported. Thus, here we assimilate and elaborate on several available action mechanisms to maximize the photothermal conversion efficiency (PCE) of organic dyes. Moreover, we also propose several potential challenges that require substantial future work to address.