Light-Promoted Lysosomal Escape of a Phthalocyanine and Antisense Oligonucleotide-Complexed G-Quadruplex for Dual Photodynamic and Antisense Therapy

• DOI: 10.1021/acsptsci.4c00384
• Publication Date: 2024-09-25T16:24:19Z
• Authors: Dick Yan Tam; Wendy K. M. Lau; Yosephine Tania L...; Dennis K. P. Ng
• Keywords: G-quadruplex

Combination therapy has been proven as an effective strategy for cancer treatment. To this end, we report herein a self-assembled nucleic acid-based complex dual photodynamic and antisense therapy. It contains nucleolin-targeting As1411-based G-quadruplex platform, partially hybridized oligonucleotide 4625, which can inhibit the antiapoptotic protein B cell lymphoma-xL inducing apoptotic death, zinc(II) phthalocyanine (ZnPc)-based photosensitizer held by noncovalent interactions. Through series of in vitro experiments, have demonstrated that DNA be internalized selectively to nucleolin-overexpressed MCF-7 A549 cells through receptor-mediated endocytosis is localized lysosomes. Upon light irradiation, photosensitization ZnPc triggers formation reactive oxygen species killing promotes lysosomal escape 4625 The combined therapeutic effect eliminate effectively with half maximal inhibitory concentration ca. 0.5 μM.