Advanced Nanoplatform Mediated by CRISPR-Cas9 and Aggregation-Induced Emission Photosensitizers to Boost Cancer Theranostics

Immunotherapy combined with phototherapy is emerging as a promising strategy to treat omnipotent cancers. In this study, a clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) system, aggregation-induced emission (AIE) photosensitizer (PS) and surface coatin...

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Bibliographic Details
Published in:ACS nano 2024-12, Vol.18 (48), p.33168-33180
Main Authors: Wang, Yuanwei, Chen, Penghang, Wen, Haifei, Gui, Yixiong, Yan, Dingyuan, Huang, Di, Wang, Dong, Tang, Ben Zhong, Tan, Hui
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Line, Tumor
Cell Proliferation - drug effects
CRISPR-Cas Systems - genetics
Drug Screening Assays, Antitumor
Humans
Immunotherapy
Mice
Mice, Inbred BALB C
Nanoparticles - chemistry
Neoplasms - diagnostic imaging
Neoplasms - genetics
Neoplasms - pathology
Neoplasms - therapy
Photosensitizing Agents - chemistry
Photosensitizing Agents - pharmacology
Reactive Oxygen Species - metabolism
Theranostic Nanomedicine
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Summary:Immunotherapy combined with phototherapy is emerging as a promising strategy to treat omnipotent cancers. In this study, a clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) system, aggregation-induced emission (AIE) photosensitizer (PS) and surface coating of polyethylene imine/hyaluronic acid were combined to construct a multifunctional nanoplatform, denoted as TCPH nanoparticles (NPs), for comprehensive cancer theranostics. TCPH NPs are featured by intrinsic functions including efficient reactive oxygen species (ROS) production, good photothermal conversion, programmed death-ligand 1 (PD-L1)-eliminating capability, and effective intracellular transport. The generated ROS and hyperthermia do not only achieve primary tumor elimination but also regulate the tumor immune microenvironment. Genomic disruption of PD-L1 conspicuously augments its therapeutic efficacy, especially in tumor metastasis and recurrence. Exceptional multimodal imaging navigation has also been developed. Excellent theranostics performance was substantiated in diverse tumor models, implying that this synergistic strategy of phototheranostics and immunotherapy provides a paradigm shift in emerging CRISPR-mediated nanomedicines.
ISSN:1936-0851
1936-086X
1936-086X
DOI:10.1021/acsnano.4c11757