An Acceptor-Donor-Acceptor Structured Small Molecule for Effective NIR Triggered Dual Phototherapy of Cancer

Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is regarded as a more effective method for cancer treatment than single PDT or PTT. However, development of single component and near-infrared (NIR) triggered agents for efficient dual phototherapy remains a challenge. Herein, a simple strategy to develop dual-functional small-molecules-based photosensitizers for combined PDT and PTT treatment is proposed through: 1) finely modulating HOMO-LUMO energy levels to regulate the intersystem crossing (ISC) process for effective singlet oxygen (O-1(2)) generation for PDT; 2) effectively inhibiting fluorescence via strong intramolecular charge transfer (ICT) to maximize the conversion of photo energy to heat for PTT or ISC process for PDT. An acceptor-donor-acceptor (A-D-A) structured small molecule (CPDT) is designed and synthesized. The biocompatible nanoparticles, FA-CNPs, prepared by encapsulating CPDT directly with a folate functionalized amphipathic copolymer, present strong NIR absorption, robust photostability, cancer cell targeting, high photothermal conversion efficiency as well as efficient O-1(2) generation under single 808 nm laser irradiation. Furthermore, synergistic PDT and PTT effects of FA-CNPs in vivo are demonstrated by significant inhibition of tumor growth. The proposed strategy may provide a new approach to reasonably design and develop safe and efficient photosensitizers for dual phototherapy against cancer.