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• W4380450093 abstract "Redox heterogeneity of tumor cells has become one of the key factors leading to the failure of conventional photodynamic therapy (PDT). Exploration of a distinctive therapeutic strategy addressing heterogeneous predicaments is an appealing yet highly challenging task. Herein, a multiple stimuli-responsive nanoCRISPR (Must-nano) with spatial arrangement peculiarities in nanostructure and intracellular delivery is fabricated to overcome redox heterogeneity at both genetic and phenotypic levels for tumor-specific activatable PDT. Must-nano consists of a redox-sensitive core loading CRISPR/Cas9 targeting hypoxia-inducible factors-1α (HIF-1α) and a rationally designed multiple-responsive shell anchored by chlorin e6 (Ce6). Benefiting from the perfect coordination of structure and function, Must-nano avoids enzyme/photodegradation of the CRISPR/Cas9 system and exerts prolonged circulation, precise tumor recognition, and cascade-responsive performances to surmount tumor extra/intracellular barriers. After internalization into tumor cells, Must-nano could undergo hyaluronidase-triggered self-disassembly with charge reversal and rapid endosomal escape, followed by site-specific release and spatially asynchronous delivery of Ce6 and CRISPR/Cas9 under stimulations of redox signals, which not only improves tumor vulnerability to oxidative stress by complete HIF-1α disruption but also destroys the intrinsic antioxidant mechanism through glutathione depletion, thereby homogenizing redox-heterogeneous cells into oxidative stress-sensitive cell subsets. Under laser irradiation, Must-nano eventually exhibits optimal potency to amplify oxidative damage, effectively inhibiting the growth and hypoxia survival of redox-heterogeneous tumor in vitro and in vivo. Overall, our redox homogenization tactic significantly maximizes PDT efficacy and offers a promising strategy to overcome tumor redox heterogeneity in the development of antitumor therapies." @default.
• W4380450093 created "2023-06-14" @default.
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• W4380450093 date "2023-06-13" @default.
• W4380450093 modified "2023-10-18" @default.
• W4380450093 title "A Multiple Stimuli-Responsive NanoCRISPR Overcomes Tumor Redox Heterogeneity to Augment Photodynamic Therapy" @default.
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• W4380450093 doi "https://doi.org/10.1021/acsnano.3c00940" @default.
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• W4380450093 hasPublicationYear "2023" @default.
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