All-in-One Heptamethine Cyanine Amphiphiles for Dual Imaging-Guided Chemo-Photodynamic-Photothermal Therapy of Breast Cancer

Developing a theranostic system that integrates multimodal imaging, synergistic therapeutic, and formulation entities is a promising strategy for efficient cancer treatment. However, the complexity and safety concerns of multiple functional entities hinder their clinical translation. Herein, versatile all-in-one heptamethine cyanine amphiphiles (PEG-Cy-Fs) with multiple favorable capabilities, including fluorine-19 magnetic resonance imaging (F-19 MRI), near-infrared fluorescence imaging (NIR FLI), photodynamic therapy (PDT), photothermal therapy (PTT), polyethylene glycolation (PEGylation) and high biocompatibility, are developed for the convenient construction of theranostic platforms. Amphiphiles PEG-Cy-Fs are synthesized on a multi-hundred-milligram scale with high efficacy, which self-assembled with a chemotherapy drug tamoxifen (TAM) into monodisperse and stable nanoparticles (SoFoTm/PEG-Cy-F-18) with turned on FLI, sensitive F-19 MRI, mitochondria-targeting ability, high PDT and PTT efficacy, and PEGylation-optimized pharmacokinetics. The selective accumulation of SoFoTm/PEG-Cy-F-18 in xenograft MCF-7 tumor with a long retention time (>10 days) enabled F-19 MRI-NIR FLI-guided chemo-photodynamic-photothermal therapy (chemo-PDT-PTT) of breast cancer with high therapeutical index in mice. The all-in-one heptamethine cyanine amphiphile may facilitate the convenient and standardized preparation of high-performance theranostics systems for clinical translation.

Automated summary

Developing a theranostic system that integrates multimodal imaging, synergistic therapeutic, and formulation entities is a promising strategy for efficient cancer treatment. In this study, versatile all-in-one heptamethine cyanine amphiphiles (PEG-Cy-Fs) were developed for the convenient construction of theranostic platforms. These amphiphiles self-assembled with a chemotherapy drug tamoxifen (TAM) into stable nanoparticles (SoFoTm/PEG-Cy-F-18) with multiple capabilities, enabling the targeted chemo-photodynamic-photothermal therapy of breast cancer with high therapeutic index in mice.