National Nano Center Makes Progress in Upconversion Photodynamic Therapy

[ Instrument Network Instrument R & D ] Recently, Li Lele and Zhao Yuliang's group at the National Nanoscience Center of the Chinese Academy of Sciences have made new progress in upconversion-mediated photodynamic therapy. Related research results "Nd3 + -Sensitized Upconversion Metal-Organic Frameworks for Mitochondria-Targeted Amplified Photodynamic Therapy" were published in "German Applied Chemistry" (Angewandte Chemie International Edition, 2019, DOI: 10.1002 / anie.201911508).

Photodynamic therapy (PDT) is a photochemical reaction-based treatment technology with high controllability and low toxic and side effects. It has been used in the clinical treatment of tumors and other related diseases. However, clinically approved photosensitizers require visible light to excite them, and their limited tissue penetration capabilities limit the application of photodynamic therapy in deep tumor treatment; moreover, complex physiological and pathological barriers limit the space of photosensitizers at the subcellular level Specific distribution, can not effectively exert the toxicity of ROS. The team has been committed to the development of up-conversion luminescence-mediated "time-space" controllable nano-biotechnology and exploring its applications in precision biological detection and disease diagnosis and treatment (Nat. Commun. 2019, 10, 2839; J. Am. Chem. Soc. 2019, 141, 7056; Angew. Chem. Int. Ed. 2019, 58, 14877; J. Am. Chem. Soc. 2018. 140, 578; J. Am. Chem. Soc. 2017, 139, 13804). Recently, the team developed a photochromic up-conversion nano-photosensitive system by introducing light-opening photomolecules, and realized precise photodynamic therapy with dual-wavelength near-infrared light programming. The related results were published as cover articles in Chemical Science (2019, 10, 10231-10239).

Based on the previous work, they designed and constructed the Janus nanostructure of Nd3 + ion-sensitized up-conversion metal-organic framework, which realized near-infrared light-triggered and targeted mitochondrial amplification photodynamic therapy. The team used epitaxial growth to synthesize Nd3 + ion-doped upconverted nanoparticles (UCNPs) with core-shell structure as seeds, and then controlled the porphyrin-based metal-organic framework materials (MOFs) using an interface-induced self-assembly strategy. Its surface grows anisotropically, and a nanophotosensitizer with the structure of Janus (the name of the two-faced god in ancient Roman mythology) is prepared; the surface asymmetry is further utilized to give the target specificity for mitochondria. Sex. Under the excitation of near-infrared light at 808 nm, UCNP in Janus nanophotosensitizer captures low-energy photons, and then transfers energy to nearby MOF nanoparticles through resonance energy transfer, thereby specifically generating singlet oxygen in the mitochondria to realize photodynamics. treatment. Importantly, regulating the dynamic balance of ROS in mitochondria at the subcellular level can activate the cell death mechanism to amplify the effect of photodynamic therapy. In addition, the use of 808 nm excitation light can effectively avoid the thermal effects of conventional 980 nm excitation up-conversion luminescence and the problem of damage to normal tissues, which improves the safety of laser applications. This work provides a new idea for efficient photodynamic therapy of tumors. Combining near-infrared light activation technology and precise space control technology is a new direction for the development of next-generation PDT systems.

Liu Chang, PhD Liu Bei, and associate researcher Zhao Jian, the joint graduates of the National Center for Nanoscience and Technology, are the co-first authors of the dissertation. The research was supported by the National Talent Program and the National Natural Science Foundation.