A Near-Infrared Organoplatinum(II) Metallacycle Conjugated with Heptamethine Cyanine for Trimodal Cancer Therapy

Abstract

Discrete Pt(II) metallacycles have attracted particular attention for the chemotherapeutic treatment of cancer. However, a single chemotherapy cannot simultaneously balance efficiency and safety because the continuous administration throughout the entire therapy period will lead to inefficient therapy and potentially long-term systemic toxicity. Therefore, the development of a novel organoplatinum(II) metallacycle with multimodal treatment capabilities is urgently needed to overcome these issues. Herein, a discrete Pt(II) metallacycle (SCY) bearing the near-infrared (NIR) photosensitizer heptamethine cyanine was fabricated and further encapsulated by amphiphilic 1,2-distearoyl-sn-glycero-3-phosphoetha-nolamine-N-methoxy(polyethyleneglycol) (DSPE-mPEG) to form P@SCY nanoparticles. Heptamethine cyanine, which has excellent photoconversion efficiency, can generate reactive oxygen species (ROS) and heat simultaneously, and the cyanine moiety can target mitochondria in cancer cells due to their quaternary ammonium salt cations, which improve the effect of phototherapy. Due to its excellent phototherapy and chemotherapy properties, P@SCY exhibited remarkable trimodal therapeutic effects [chemo-/ photodynamic therapy (PDT)/photothermal therapy (PTT)] against cancer cells (HepG2 cells, MCF-7 cells, and 4T1 cells) in vitro. Furthermore, in vivo results also confirmed that P@SCY had superior antitumor properties with minimal side effects in the 4T1 tumor model. This work presents a practicable approach to develop a multifunctional organoplatinum(II) metallacycle for multimodal tumor therapy.