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GRP75-driven, cell-...
GRP75-driven, cell-cycle-dependent macropinocytosis of Tat/pDNA-Ca2+ nanoparticles underlies distinct gene therapy effect in ovarian cancer
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- Su, Linjia (författare)
- Nankai Univ, Sch Med, Dept Cell Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China.
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- Sun, Zhe (författare)
- Tianjin Univ, Sch Life Sci, Weijin Rd 92, Tianjin 300072, Peoples R China.
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- Qi, Fangzheng (författare)
- Nankai Univ, Sch Med, Dept Cell Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China.
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- Su, Huishan (författare)
- Nankai Univ, Sch Med, Dept Cell Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China.
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- Qian, Luomeng (författare)
- Nankai Univ, Sch Med, Dept Cell Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China.
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- Li, Jing (författare)
- Nankai Univ, Sch Med, Dept Cell Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China.
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- Zuo, Liang (författare)
- Nankai Univ, Sch Med, Dept Cell Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China.
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- Huang, Jinhai (författare)
- Tianjin Univ, Sch Life Sci, Weijin Rd 92, Tianjin 300072, Peoples R China.
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- Yu, Zhilin (författare)
- Nankai Univ, Coll Chem, State Key Lab Med Chem Biol, Weijin Rd 94, Tianjin 300071, Peoples R China.
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- Li, Jin-Ping (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Chen, Zhinan (författare)
- Fourth Mil Med Univ, Natl Translat Sci Ctr Mol Med, Dept Cell Biol, State Key Lab Canc Biol, Xian 710032, Peoples R China.
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- Zhang, Sihe (författare)
- Nankai Univ, Sch Med, Dept Cell Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China.
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Nankai Univ, Sch Med, Dept Cell Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China Tianjin Univ, Sch Life Sci, Weijin Rd 92, Tianjin 300072, Peoples R China. (creator_code:org_t)
- 2022-07-20
- 2022
- Engelska.
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Ingår i: Journal of Nanobiotechnology. - : Springer Nature. - 1477-3155. ; 20:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Practice of tumor-targeted suicide gene therapy is hampered by unsafe and low efficient delivery of plasmid DNA (pDNA). Using HIV-Tat-derived peptide (Tat) to non-covalently form Tat/pDNA complexes advances the delivery performance. However, this innovative approach is still limited by intracellular delivery efficiency and cell-cycle status. In this study, Tat/pDNA complexes were further condensed into smaller, nontoxic nanoparticles by Ca2+ addition. Formulated Tat/pDNA-Ca2+ nanoparticles mainly use macropinocytosis for intercellular delivery, and their macropinocytic uptake was persisted in mitosis (M-) phase and highly activated in DNA synthesis (S-) phase of cell-cycle. Over-expression or phosphorylation of a mitochondrial chaperone, 75-kDa glucose-regulated protein (GRP75), promoted monopolar spindle kinase 1 (MPS1)-controlled centrosome duplication and cell-cycle progress, but also driven cell-cycle-dependent macropinocytosis of Tat/pDNA-Ca2+ nanoparticles. Further in vivo molecular imaging based on DF (Fluc-eGFP)-TF (RFP-Rluc-HSV-ttk) system showed that Tat/pDNA-Ca2+ nanoparticles exhibited highly suicide gene therapy efficiency in mouse model xenografted with human ovarian cancer. Furthermore, arresting cell-cycle at S-phase markedly enhanced delivery performance of Tat/pDNA-Ca2+ nanoparticles, whereas targeting GRP75 reduced their macropinocytic delivery. More importantly, in vivo targeting GRP75 combined with cell-cycle or macropinocytosis inhibitors exhibited distinct suicide gene therapy efficiency. In summary, our data highlight that mitochondrial chaperone GRP75 moonlights as a biphasic driver underlying cell-cycle-dependent macropinocytosis of Tat/pDNA-Ca2+ nanoparticles in ovarian cancer.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Nyckelord
- Macropinocytosis
- Cell-cycle
- Glucose-regulated protein
- Tat/pDNA-Ca2+ nanoparticle
- Suicide gene therapy
- Ovarian cancer
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Su, Linjia
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Sun, Zhe
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Qi, Fangzheng
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Su, Huishan
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Qian, Luomeng
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Li, Jing
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visa fler...
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Zuo, Liang
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Huang, Jinhai
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Yu, Zhilin
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Li, Jin-Ping
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Chen, Zhinan
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Zhang, Sihe
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Cellbiologi
- Artiklar i publikationen
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Journal of Nanob ...
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Uppsala universitet