Gold nanorod enhanced conjugated polymer/photosensitizer composite nanoparticles for simultaneous two-photon excitation fluorescence imaging and photodynamic therapy

Two-photon photodynamic therapy (2P-PDT) is a novel minimal invasive cancer treatment method with advantages of deep penetration and intrinsic three-dimensionally localized activation to precisely target cancerous tissues. However, the therapeutic efficacy of 2P-PDT is limited by small two-photon absorption cross sections of conventional organic photosensitizers. In addition, traditional photosensitizers generally exhibit weak emission and lack imaging modality. In this work, conjugated polymers and gold nanorods (Au NRs) were integrated to fabricate nano-sized photosensitizers to improve the performance of molecular photosensitizers for 2P-PDT. A molecular photosensitizer, tetraphenylporphyrin, was encapsulated into the conjugated polymer PFV to form conjugated polymer nanoparticles (CPNs), which were then covalently linked to silica coated Au NRs. In these integrated nanoparticles, the two-photon optical properties of tetraphenylporphyrin were first enhanced by fluorescence resonance energy transfer from PFV, then further enhanced by Au NRs through plasmon resonance. A silica shell was utilized as the spacer between Au NRs and CPNs to optimize the enhancement effects. Through the combined enhancement effects of energy transfer and plasmon resonance, two-photon excitation fluorescence and two-photon induced singlet oxygen generation of tetraphenylporphyrin were enhanced by up to 980- and 792-fold, respectively, at a silica spacer thickness of 9 nm. The application of these nanoparticles as photosensitizers for simultaneous two-photon imaging and 2P-PDT treatment have been demonstrated on HeLa cancer cells with high brightness and significantly enhanced cancer cell killing efficiency. These nanoparticles can act as promising nano-photosensitizers for 2P-PDT with simultaneous imaging modality.