Cold-Responsive Hyaluronated Upconversion Nanoplatform for Transdermal Cryo-Photodynamic Cancer Therapy
발표자
Molkenova Anara (Pusan National University)
연구책임자
김기수 (부산대학교)
초록
내용
Upconversion photodynamic therapy (UPDT) has emerged as a novel localized therapeutic modality for treating various cancers through remote deep tissue photoactivation of ultraviolet and visible emissions of upconversion nanoparticles (UCNPs). However, further advances in UPDT are still restricted by the poor brightness of UCNPs to achieve sufficient therapeutic outcomes under skin-safe NIR laser power irradiation. Recently, it has been reported that the luminescence of UCNPs is greatly enhanced at cryogenic temperatures by suppressing thermal quenching. Therefore, in our study, we prepared 808-nm excitable UCNPs using a facile and accelerated synthetic protocol, which have been proven to exhibit a 2.5-fold photoluminescence intensity enhancement after exposure to low temperature conditions. Therefore, a new approach to combine cryotherapy and upconversion photodynamic therapy (Cryo-UPDT) is proposed in this study. We designed a therapeutic nanoplatform that integrates porous silica-coated UCNPs, chlorin e6 photosensitizer, and hyaluronic acid (UCNPs@SiO2-Ce6-HA), to treat skin cancer with exogenous 808 nm NIR laser excitation. An ex vivo study showed that a cryo-driven boost of upconversion brightness led to a 3.15-times increase of the cytotoxic 1O2 generation by photosensitized Ce6 in the nanoplatform. In vitro studies validated the biosafety, cancer targeting, and NIR-assisted cancer-cell killing properties of the UCNPs@SiO2-Ce6-HA nanoplatform. Moreover, excellent transdermal delivery capabilities were confirmed using porcine skin models. Thus, the developed nanoplatform can effectively penetrate deep into the cancerous tissue and produce a synergistic tumoricidal effect under consecutive freezing and NIR laser irradiation. As a result, the proposed Cryo-UPDT treatment demonstrated an impressive 1.44 times higher tumor eradication in melanoma-bearing mice than PDT treatment alone. In summary, this study proves that Cryo-UPDT represents a novel and valid therapeutic strategy.