TY - JOUR
T1 - Deep-penetrating photodynamic therapy with KillerRed mediated by upconversion nanoparticles
AU - Liang, Liuen
AU - Lu, Yiqing
AU - Zhang, Run
AU - Care, Andrew
AU - Ortega, Tiago A.
AU - Deyev, Sergey M.
AU - Qian, Yi
AU - Zvyagin, Andrei V.
PY - 2017
Y1 - 2017
N2 - The fluorescent protein KillerRed, a new type of biological photosensitizer, is considered as a promising substitute for current synthetic photosensitizes used in photodynamic therapy (PDT). However, broad application of this photosensitiser in treating deep-seated lesions is challenging due to the limited tissue penetration of the excitation light with the wavelength falling in the visible spectral range. To overcome this challenge, we employ upconversion nanoparticles (UCNPs) that are able to convert deep-penetrating near infrared (NIR) light to green light to excite KillerRed locally, followed by the generation of reactive oxygen species (ROS) to kill tumour cells under centimetre-thick tissue. The photosensitizing bio-nanohybrids, KillerRed-UCNPs, are fabricated through covalent conjugation of KillerRed and UCNPs. The resulting KillerRed-UCNPs exhibit excellent colloidal stability in biological buffers and low cytotoxicity in the dark. Cross-comparison between the conventional KillerRed and UCNP-mediated KillerRed PDT demonstrated superiority of KillerRed-UCNPs photosensitizing by NIR irradiation, manifested by the fact that ∼70% PDT efficacy was achieved at 1-cm tissue depth, whereas that of the conventional KillerRed dropped to ∼7%. Statement of Significance KillerRed is a protein photosensitizer that holds promise as an alternative for the existing hydrophobic photosensitizers that are widely used in clinical photodynamic therapy (PDT). However, applications of KillerRed to deep-seated tumours are limited by the insufficient penetration depth of the excitation light in highly scattering and absorbing biological tissues. Herein, we reported the deployment of upconversion nanoparticles (UCNPs) to enhance the treatment depth of KillerRed by converting the deep-penetrating near-infrared (NIR) light to upconversion photoluminescence and activating the PDT effect of KillerRed under deep tissues. This work demonstrated clear potential of UCNPs as the NIR-to-visible light converter to overcome the light penetration limit that has plagued PDT application for many years.
AB - The fluorescent protein KillerRed, a new type of biological photosensitizer, is considered as a promising substitute for current synthetic photosensitizes used in photodynamic therapy (PDT). However, broad application of this photosensitiser in treating deep-seated lesions is challenging due to the limited tissue penetration of the excitation light with the wavelength falling in the visible spectral range. To overcome this challenge, we employ upconversion nanoparticles (UCNPs) that are able to convert deep-penetrating near infrared (NIR) light to green light to excite KillerRed locally, followed by the generation of reactive oxygen species (ROS) to kill tumour cells under centimetre-thick tissue. The photosensitizing bio-nanohybrids, KillerRed-UCNPs, are fabricated through covalent conjugation of KillerRed and UCNPs. The resulting KillerRed-UCNPs exhibit excellent colloidal stability in biological buffers and low cytotoxicity in the dark. Cross-comparison between the conventional KillerRed and UCNP-mediated KillerRed PDT demonstrated superiority of KillerRed-UCNPs photosensitizing by NIR irradiation, manifested by the fact that ∼70% PDT efficacy was achieved at 1-cm tissue depth, whereas that of the conventional KillerRed dropped to ∼7%. Statement of Significance KillerRed is a protein photosensitizer that holds promise as an alternative for the existing hydrophobic photosensitizers that are widely used in clinical photodynamic therapy (PDT). However, applications of KillerRed to deep-seated tumours are limited by the insufficient penetration depth of the excitation light in highly scattering and absorbing biological tissues. Herein, we reported the deployment of upconversion nanoparticles (UCNPs) to enhance the treatment depth of KillerRed by converting the deep-penetrating near-infrared (NIR) light to upconversion photoluminescence and activating the PDT effect of KillerRed under deep tissues. This work demonstrated clear potential of UCNPs as the NIR-to-visible light converter to overcome the light penetration limit that has plagued PDT application for many years.
KW - Photodynamic therapy
KW - Photosensitizing protein
KW - Upconversion nanoparticles
KW - Energy transfer
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85010425294&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2017.01.004
DO - 10.1016/j.actbio.2017.01.004
M3 - Article
C2 - 28063989
AN - SCOPUS:85010425294
SN - 1742-7061
VL - 51
SP - 461
EP - 470
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -