Affiliation:
1. Frontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering (MOE) School of Chemical Engineering and Technology Tianjin University Tianjin 300350 P. R. China
2. State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer Institute Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 P. R. China
3. Department of Chemistry State Key Laboratory of Molecular Engineering of Polymers Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials College of Chemistry and Materials Fudan University Shanghai 200438 P. R. China
4. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China
Abstract
AbstractPhotodynamic therapy (PDT) depends on the light‐irradiated exciting of photosensitizer (PS) to generate reactive oxygen species (ROS), which faces challenges and limitations in hypoxia and antioxidant response of cancer cells, and limited tissue‐penetration of light. Herein, a multifunctional DNA/upconversion nanoparticles (UCNPs) complex is developed which enables controlled co‐delivery of CRISPR‐Cas9, hemin, and protoporphyrin (PP) for synergistic PDT. An ultralong single‐stranded DNA (ssDNA) is prepared via rolling circle amplification (RCA), which contains recognition sequences of single guide RNA (sgRNA) for loading Cas9 ribonucleoprotein (RNP), G‐quadruplex sequences for loading hemin and PP, and linker sequences for combining UCNP. Cas9 RNP cleaves the antioxidant regulator nuclear factor E2‐related factor 2 (Nrf2), improving the sensitivity of cancer cells to ROS, and enhancing the synergistic PDT effect. The G‐quadruplex/hemin DNAzyme mimicks horseradish peroxidase (HRP) to catalyze the endogenous H2O2 to O2, overcoming hypoxia condition in tumors. The introduced UCNP converts NIR irradiation with deep tissue penetration to light with shorter wavelength, exciting PP to transform the abundant O2 to 1O2. The integration of gene editing and PDT allows substantial accumulation of 1O2 in cancer cells for enhanced cell apoptosis, and this synergistic PDT has shown remarkable therapeutic efficacy in a breast cancer mouse model.
Funder
National Natural Science Foundation of China
Cited by
6 articles.
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