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author：

Jiang, Yifan (Jiang, Yifan.) [1] | Liu, Yichang (Liu, Yichang.) [2] | Wang, Min (Wang, Min.) [3] | Li, Zhi (Li, Zhi.) [4] | Su, Lichao (Su, Lichao.) [5] | Xu, Xin (Xu, Xin.) [6] | Xing, Chao (Xing, Chao.) [7] | Li, Jinyu (Li, Jinyu.) [8] | Lin, Lisen (Lin, Lisen.) [9] | Lu, Chunhua (Lu, Chunhua.) [10] | Yang, Huanghao (Yang, Huanghao.) [11]

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EI

Abstract：

Multiple　drug-resistance　mechanisms　originate　from　defensive　pathways　in　cancer　and　are　associated　with　the　unsatisfied　efficacy　of　chemotherapy.　The　combination　of　small　interfering　RNA　(siRNA)　and　chemotherapeutics　provides　a　strategy　for　reducing　drug　efflux　but　requires　more　delivery　options　for　clinical　translation.　Herein,　multidrug　resistance　protein　1　(MDR1)　siRNA　is　used　as　the　skeleton　to　assemble　chemotherapeutic　cisplatin　(CDDP)　and　divalent　copper　ion　(Cu2+)　for　constructing　a　carrier-free　Cu-siMDR-CDDP　system.　Cu-siMDR-CDDP　specifically　responds　and　disassembles　in　the　acidic　tumor　microenvironment　(TME).　The　released　CDDP　activates　cascade　bioreactions　of　NADPH　oxidases　and　superoxide　dismutase　to　generate　hydrogen　peroxide　(H2O2).　Then　a　Cu2+-catalyzed　Fenton-like　reaction　transforms　H2O2　to　hydroxyl　radicals　(HO•)　and　causes　glutathione　(GSH)　depletion　to　disrupt　the　redox　adaptation　mechanism　of　drug-resistant　cancer　cells.　Besides,　delivery　of　MDR1　siRNA　is　facilitated　by　HO•-triggered　lysosome　destruction,　thus　inhibiting　P-glycoprotein　(P-gp)　expression　and　CDDP　efflux.　The　unique　design　of　Cu-siMDR-CDDP　is　to　exploit　siRNA　as　building　blocks　in　regulating　the　self-assembly　behavior,　and　integration　of　functional　units　simultaneously　alleviates　limitations　caused　by　drug-resistance　mechanisms.　Such　a　carrier-free　system　shows　synergistic　chemo/chemodynamic/RNA　interference　therapy　in　suppressing　tumor　growth　in　vivo　and　has　the　reference　value　for　overcoming　drug　resistance.　©

Keyword：

Chemotherapy Controlled drug delivery Copper compounds Diseases Enzymes Glycoproteins Metal ions Oxidation RNA Self assembly Targeted drug delivery Tumors

Community：

  • [ 1 ] [Jiang, Yifan]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou; 350108, China
  • [ 2 ] [Liu, Yichang]National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou; 350108, China
  • [ 3 ] [Wang, Min]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou; 350108, China
  • [ 4 ] [Li, Zhi]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou; 350108, China
  • [ 5 ] [Su, Lichao]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou; 350108, China
  • [ 6 ] [Xu, Xin]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou; 350108, China
  • [ 7 ] [Xing, Chao]Fujian Key Laboratory of Functional Marine Sensing Materials, Center for Advanced Marine Materials and Smart Sensors, Minjiang University, Fuzhou; 350108, China
  • [ 8 ] [Li, Jinyu]National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou; 350108, China
  • [ 9 ] [Lin, Lisen]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou; 350108, China
  • [ 10 ] [Lu, Chunhua]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou; 350108, China
  • [ 11 ] [Yang, Huanghao]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou; 350108, China

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Source ：

ACS Applied Materials and Interfaces

ISSN： 1944-8244

Year： 2022

Issue： 1

Volume： 14

Page： 361-372

9 . 5

JCR@2022

8 . 5 0 0

JCR@2023

ESI HC Threshold：91

JCR Journal Grade：1

CAS Journal Grade：2

Cited Count：

WoS CC Cited Count：

SCOPUS Cited Count： 20

ESI Highly Cited Papers on the List： 0 Unfold All

WanFang Cited Count：

Chinese Cited Count：

30 Days PV： 3

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