Synergistic photothermal cancer immunotherapy by Cas9 ribonucleoprotein-based copper sulfide nanotherapeutic platform targeting PTPN2

Yan, Tao; Yang, Kaiyong; Chen, Chao; Zhou, Zhiruo; Shen, Pengfei; Jia, Yuanyuan; Yu, Xue; Zhang, Zhenyu; Shen, Xu; Han, Xin

doi:10.1016/j.biomaterials.2021.121233

Cited by 52 publications

(36 citation statements)

References 45 publications

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“…2d-f and S12, † HDHF exhibited typical concentration-and power-dependent photothermal conversion performance, which was consistent with HCuS. 49,50 The temperature of HDHF (80 ppm) could increase from 24.2 °C to 65.4 °C after 6 minutes of 808 nm laser irradiation (1.25 W cm −2 ), higher than that of HCuS under the same conditions (Fig. 2d, e and S13 †).…”

Section: Synthesis and Characterization Of The Nanoreactorsupporting

confidence: 64%

A dual gate-controlled intelligent nanoreactor enables collaborative precise treatment for cancer nanotherapy

et al. 2022

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Section: Synthesis and Characterization Of The Nanoreactorsupporting

confidence: 64%

A dual gate-controlled intelligent nanoreactor enables collaborative precise treatment for cancer nanotherapy

et al. 2022

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“…First, photothermal conversion is a commonly utilized light-triggered phenomenon in biomedical applications, such as photothermal therapy [185,186]. Photothermal agents, including organic (e.g., indocyanine green and polydopamine) and inorganic ones (e.g., gold NPs, CuS NPs and graphene), can convert light into heat energy, leading to temperature increases [187][188][189][190][191][192]. Notably, it has been validated that photothermal effects can also facilitate endo/lysosomal escape and cleavage of thermal-sensitive chemical bonds to achieve on-demand payload release and activation [193,194].…”

Section: Light-responsive Crispr-cas9 Deliverymentioning

confidence: 99%

Stimuli-responsive nanoformulations for CRISPR-Cas9 genome editing

et al. 2022

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The CRISPR-Cas9 technology has changed the landscape of genome editing and has demonstrated extraordinary potential for treating otherwise incurable diseases. Engineering strategies to enable efficient intracellular delivery of CRISPR-Cas9 components has been a central theme for broadening the impact of the CRISPR-Cas9 technology. Various non-viral delivery systems for CRISPR-Cas9 have been investigated given their favorable safety profiles over viral systems. Many recent efforts have been focused on the development of stimuli-responsive non-viral CRISPR-Cas9 delivery systems, with the goal of achieving efficient and precise genome editing. Stimuli-responsive nanoplatforms are capable of sensing and responding to particular triggers, such as innate biological cues and external stimuli, for controlled CRISPR-Cas9 genome editing. In this Review, we overview the recent advances in stimuli-responsive nanoformulations for CRISPR-Cas9 delivery, highlight the rationale of stimuli and formulation designs, and summarize their biomedical applications.

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“…In one study, PTPN2 was targeted by a compound composed of copper-sulfate nano-photothermal materials carrying Cas9 and oligonucleotides to generate a mutation in PTPN2. Its use in mice caused tumor hyperthermia, PTPN2 depletion, increased T cell infiltration into the tumor, and higher intratumoral IFN-γ and TNF-α levels ( 91 ). Controlled enhancement of PTPN2 function may be beneficial in autoimmune disease, while targeted inhibition of PTPN2 may help enhance the immune response to cancer.…”

Section: Ptpn2mentioning

confidence: 99%

Combination Approaches to Target PD-1 Signaling in Cancer

2022

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Cancer remains the second leading cause of death in the US, accounting for 25% of all deaths nationwide. Immunotherapy techniques bolster the immune cells’ ability to target malignant cancer cells and have brought immense improvements in the field of cancer treatments. One important inhibitory protein in T cells, programmed cell death protein 1 (PD-1), has become an invaluable target for cancer immunotherapy. While anti-PD-1 antibody therapy is extremely successful in some patients, in others it fails or even causes further complications, including cancer hyper-progression and immune-related adverse events. Along with countless translational studies of the PD-1 signaling pathway, there are currently close to 5,000 clinical trials for antibodies against PD-1 and its ligand, PD-L1, around 80% of which investigate combinations with other therapies. Nevertheless, more work is needed to better understand the PD-1 signaling pathway and to facilitate new and improved evidence-based combination strategies. In this work, we consolidate recent discoveries of PD-1 signaling mediators and their therapeutic potential in combination with anti-PD-1/PD-L1 agents. We focus on the phosphatases SHP2 and PTPN2; the kinases ITK, VRK2, GSK-3, and CDK4/6; and the signaling adaptor protein PAG. We discuss their biology both in cancer cells and T cells, with a focus on their role in relation to PD-1 to determine their potential in therapeutic combinations. The literature discussed here was obtained from a search of the published literature and ClinicalTrials.gov with the following key terms: checkpoint inhibition, cancer immunotherapy, PD-1, PD-L1, SHP2, PTPN2, ITK, VRK2, CDK4/6, GSK-3, and PAG. Together, we find that all of these proteins are logical and promising targets for combination therapy, and that with a deeper mechanistic understanding they have potential to improve the response rate and decrease adverse events when thoughtfully used in combination with checkpoint inhibitors.

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Synergistic photothermal cancer immunotherapy by Cas9 ribonucleoprotein-based copper sulfide nanotherapeutic platform targeting PTPN2

Cited by 52 publications

References 45 publications

A dual gate-controlled intelligent nanoreactor enables collaborative precise treatment for cancer nanotherapy

A dual gate-controlled intelligent nanoreactor enables collaborative precise treatment for cancer nanotherapy

Stimuli-responsive nanoformulations for CRISPR-Cas9 genome editing

Combination Approaches to Target PD-1 Signaling in Cancer

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