A NIR-controlled CRISPR-Cas9 RNP delivery platform for sensitized mPTT via HSP90α knockout. (A) Schematic illustration of stepwise synthesis of CuS-RNP/Dox@PEI and NIR-triggered Cas9-RNP targeting HSP90α delivery for gene editing enhanced mPTT; (B, C) The tumor volumes and weights after treatments of various formulations: (I) PBS (with NIR), (II) CuS-RNP/Dox@PEI (without NIR), (III) CuS NPs (with NIR), (IV) CuS-RNP@PEI (with NIR), and (V) CuS-RNP/Dox@PEI (with NIR); (D) T7 endonuclease 1 mismatch detection assay for indels frequency analysis of tumor regions with various administrations; (E) Off-target effects analysis of tumor tissues after treatment with (IV). Mismatched bases are shown in red. (F) HSP90α staining of tumor tissues. The mean value was analyzed using t-test (n = 4, **P < 0.01 and ***P < 0.001). Reproduced with permission from [46]. Copyright 2021 Wiley.