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Tytuł:
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A DNA damage nanoamplifier for the chemotherapy of triple-negative breast cancer via DNA damage induction and repair blocking.
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Autorzy:
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Huang Y; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Dai X; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Guan Z; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Liu D; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Ren L; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Chen M; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Zeng Z; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Jiang J; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Luo Y; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
He Y; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Huang M; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Zhao C; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China. Electronic address: .
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Źródło:
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International journal of pharmaceutics [Int J Pharm] 2022 Jun 25; Vol. 622, pp. 121897. Date of Electronic Publication: 2022 Jun 08.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
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MeSH Terms:
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Triple Negative Breast Neoplasms*/drug therapy
Triple Negative Breast Neoplasms*/genetics
Triple Negative Breast Neoplasms*/pathology
Cell Line, Tumor ; DNA Damage ; Humans ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Poly(ADP-ribose) Polymerases
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Contributed Indexing:
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Keywords: DNA damage repair; Liposome; Niraparib; PARP inhibitor; Platinum(IV) prodrug; Triple-negative breast cancer
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Substance Nomenclature:
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0 (Poly(ADP-ribose) Polymerase Inhibitors)
EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
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Entry Date(s):
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Date Created: 20220611 Date Completed: 20220621 Latest Revision: 20220621
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Update Code:
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20240105
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DOI:
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10.1016/j.ijpharm.2022.121897
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PMID:
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35690308
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Due to a powerful DNA damage repair system and a lack of surface markers, there is currently no effective chemotherapy or tailored targeted therapies available for triple-negative breast cancer (TNBC) treatment. Herein, a tailored DNA damage nanoamplifier (Lipo@Nir/Pt(IV) C18 ) was engineered to simultaneously induce DNA damage and inhibit DNA reparation for highly efficient TNBC treatment. A newly synthesized Pt(IV) C18 prodrug, the DNA damaging inducer, and the hydrophobic poly(ADP-ribose) polymerases (PARPs) inhibitor niraparib, which is used as the DNA repair blocker, were concurrently encapsulated in highly biocompatible PEGylated liposomes to prepare Lipo@Nir/Pt(IV) C18 , for enhanced cancer therapy and future clinical translation. Lipo@Nir/Pt(IV) C18 with an appropriate size and excellent stability, effectively accumulated at the tumor site. After internalization by tumor cells, niraparib, a highly-selective hydrophobic PARP1 inhibitor, could exacerbate the accumulation of platinum-induced DNA lesions to induce excessive genome damage for synergistic cell apoptosis, which was evidenced by the upregulated γ-H 2 AX and cleaved-PARP levels. Importantly, Lipo@Nir/Pt(IV) C18 exhibited remarkable antitumor efficacy on TNBC without BRCA mutants in vivo with little systemic toxicity. Inspired by the concept of "synthetic lethality", this study provides an inspirational and clinically transformable nanobased DNA damaging amplification strategy for the expansion of TNBC beneficiaries and highly efficient TNBC treatment via DNA damage induction and DNA repair blocking.
(Copyright © 2022 Elsevier B.V. All rights reserved.)