Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics

Shi, Changrong; Zhang, Qianyu; Yao, Yuying; Zeng, Fantian; Du, Chao; Nijiati, Sureya; Wen, Xiang; Zhang, Xinyi; Yang, Hongzhang; Chen, Haoting; Guo, Zhide; Zhang, Xianzhong; Gao, Jinhao; Guo, Weisheng; Chen, Xiaoyuan; Zhou, Zijian

doi:10.1038/s41565-022-01261-7

Cited by 47 publications

(44 citation statements)

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“…It is interesting to note that, recently, the thiol−disulfide redox state of T cell membranes has been utilized for regulating and imaging the activity of tumor-infiltrating T cells by liposomes. 53 We have then shown that PDS1-based nanoparticle coating can indeed generate a large enhancement in transfection efficiency of plasmid DNAs of fluorescent proteins in BMSCs, with the cell viability maintained. Further improvement in transfection efficiency is expected from further optimization of the delivery method, to get closer to the transfection efficiency level of viral vectors in MSCs (∼90%).…”

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confidence: 89%

“…It is worth mentioning that in the literature PDS has not been previously tested on BMSCs. It is interesting to note that, recently, the thiol–disulfide redox state of T cell membranes has been utilized for regulating and imaging the activity of tumor-infiltrating T cells by liposomes . We have then shown that PDS1-based nanoparticle coating can indeed generate a large enhancement in transfection efficiency of plasmid DNAs of fluorescent proteins in BMSCs, with the cell viability maintained.…”

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confidence: 93%

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Mechanism-Driven Technology Development for Solving the Intracellular Delivery Problem of Hard-To-Transfect Cells

et al. 2023

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The so-called “hard-to-transfect cells” are well-known to present great challenges to intracellular delivery, but detailed understandings of the delivery behaviors are lacking. Recently, we discovered that vesicle trapping is a likely bottleneck of delivery into a type of hard-to-transfect cells, namely, bone-marrow-derived mesenchymal stem cells (BMSCs). Driven by this insight, herein, we screened various vesicle trapping–reducing methods on BMSCs. Most of these methods failed in BMSCs, although they worked well in HeLa cells. In stark contrast, coating nanoparticles with a specific form of poly(disulfide) (called PDS1) nearly completely circumvented vesicle trapping in BMSCs, by direct cell membrane penetration mediated by thiol–disulfide exchange. Further, in BMSCs, PDS1-coated nanoparticles dramatically enhanced the transfection efficiency of plasmids of fluorescent proteins and substantially improved osteoblastic differentiation. In addition, mechanistic studies suggested that higher cholesterol content in plasma membranes of BMSCs might be a molecular-level reason for the greater difficulty of vesicle escape in BMSCs.

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confidence: 89%

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confidence: 93%

Mechanism-Driven Technology Development for Solving the Intracellular Delivery Problem of Hard-To-Transfect Cells

et al. 2023

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“…A major goal of cancer theranostic NPs is to deliver the required amount of therapeutic/imaging payloads at the tumor action sites, so as to achieve optimal treatment outcomes without unwanted side effects. , The NPs can achieve targeted delivery to tumor tissues by utilizing a passive targeting strategy mediated by the enhanced permeability and retention (EPR) effect and an active targeting strategy mediated by cell specific ligands. We have extensively investigated RGD, , octreotate (TATE), ERBITUX, lactose, and fibroblast activation protein inhibitor (FAPI) as surface ligands to promote targeted delivery of NPs and achieve effective cancer therapy and imaging.…”

Section: Aims Of Np Surface Engineeringmentioning

confidence: 99%

Surface Engineering of Nanoparticles toward Cancer Theranostics

et al. 2023

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Metrics & MoreArticle Recommendations CONSPECTUS: Development of multifunctional nanoparticles (NPs) with desired properties is a significant topic in the field of nanotechnology and has been anticipated to revolutionize cancer diagnosis and treatment modalities. The surface character is one of the most important parameters of NPs that can directly affect their in vivo fate, bioavailability, and final theranostic outcomes and thus should be carefully tuned to maximize the diagnosis and treatment effects while minimizing unwanted side effects. Surface engineered NPs have utilized various surface functionality types and approaches to meet the requirements of cancer therapy and imaging. Despite the various strategies, these surface modifications generally serve similar purposes, namely, introducing therapeutic/imaging modules, improving stability and circulation, enhancing targeting ability, and achieving controlled functions. These surface engineered NPs hence could be applied in various cancer diagnosis and treatment scenarios and continuously contribute to the clinical translation of the next-generation NP-based platforms toward cancer theranostics.In this Account, we present recent advances and research efforts on the development of NP surface engineering toward cancer theranostics. First, we summarize the general strategies for NP surface engineering. Various types of surface functionalities have been applied including inorganic material-based functionality, organic material-based functionality like small molecules, polymers, nucleic acids, peptides, proteins, carbohydrates, antibodies, etc., and biomembrane-based functionality. These surface modifications can be realized by prefabrication or postfabrication functionalization, driven by covalent conjugations or noncovalent interactions. Second, we highlight the general aims of these different NPs surface functionalities. Different therapeutic and diagnostic modules, such as nanozymes, antibodies, and imaging contrast agents, have been modified on the surface of NPs to achieve theranostic function. Surface modification also can improve stability and circulation of NPs by protecting the NPs from immune recognition and clearance. In addition, to achieve targeted therapy and imaging, various targeting moieties have been attached on the NP surface to enhance active targeting ability to tissues or cells of interest. Furthermore, the NP surfaces can be tailored to achieve controlled functions which only respond to specific internal (e.g., pH, thermal, redox, enzyme, hypoxia) or external (e.g., light, ultrasound) triggers at the precise action sites. Finally, we present our perspective on the remaining challenges and future developments in this significant and rapidly evolving field. We hope this Account can offer an insightful overlook on the recent progress and an illuminating prospect on the advanced strategies, promoting more attention in this area and adoption by more scientists in various research fields, accelerating the development of NP surface engineering wit...

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“…86 Shi et al designed a fusogenic liposome to fuse with T cells to modulate and measure their activity by utilizing their surface redox degree as a chemical target. 87 These liposomes consisted of 1,2-dioleoyl- sn-glycero -3-phosphoethanolamine (DOPE), DSPE-PEG, and DOTAP. The maximized fusion efficiency was obtained when the DOTAP content reached 50%.…”

Section: Intracellular Deliverymentioning

confidence: 99%

Structural and componential design: new strategies regulating the behavior of lipid-based nanoparticlesin vivo

Zhong

Zheng

et al. 2023

Biomater. Sci.

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Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics

Cited by 47 publications

References 50 publications

Mechanism-Driven Technology Development for Solving the Intracellular Delivery Problem of Hard-To-Transfect Cells

Mechanism-Driven Technology Development for Solving the Intracellular Delivery Problem of Hard-To-Transfect Cells

Surface Engineering of Nanoparticles toward Cancer Theranostics

Structural and componential design: new strategies regulating the behavior of lipid-based nanoparticlesin vivo

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