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author:

Zhang, Honglei (Zhang, Honglei.) [1] | Wu, Yanjuan (Wu, Yanjuan.) [2] | Xu, Xiao (Xu, Xiao.) [3] | Chen, Chen (Chen, Chen.) [4] | Xue, Xiukun (Xue, Xiukun.) [5] | Xu, Ben (Xu, Ben.) [6] | Li, Tianduo (Li, Tianduo.) [7] | Chen, Zhaowei (Chen, Zhaowei.) [8] (Scholars:陈兆委)

Indexed by:

EI SCIE

Abstract:

The conventional mono-chemotherapy still suffers from unsatisfied potency for cancer therapy due to tumor heterogeneity and the occurrence of drug resistance. Combination chemotherapy based on the nanosized drug delivery systems (nDDSs) has been developed as a promising platform to circumvent the limitations of mono-chemotherapy. In this work, starting from cisplatin and curcumin (Cur), we prepared a dual drug backboned shattering polymeric nDDS for synergistic chemotherapy. By in situ polymerization of the Cur, platinum (IV) complex-based prodrug monomer (DHP), L-lysine diisocyanate (LDI), and then conjugation with a hydrophilic poly (ethylene glycol) monomethyl ether (mPEG) derivative, a backbone-type platinum (IV) and Cur linkage containing mPEG-poly(platinum-co-Cur)-mPEG (PCPt) copolymer was synthesized. Notably, the platinum (IV) (Pt (IV)) and Cur were incorporated into the hydrophobic segment of PCPt with the fixed drugs loading ratio and high drugs loading content. The batch-to-batch variability could be decreased. The resulting prodrug copolymer then self-assembled into nanoparticles (PCPt NPs) with an average diameter around 100 nm, to formulate a synergetic nDDS. Importantly, PCPt NPs could greatly improve the solubility and stability of Cur. In vitro drug release profiles have demonstrated that PCPt NPs were stable in PBS 7.4, rapid burst release was greatly decreased, and the Pt and Cur release could be largely enhanced under reductive conditions due to the complete dissociation of the hydrophobic main chain of PCPt. In vitro cell viability test indicated that PCPt NPs were efficient synergistic chemotherapy units. Moreover, PCPt NPs were synergistic for cisplatin-resistant cell lines A549/DDP cells, and they exhibited excellent reversal ability of tumor resistance to cisplatin. This work provides a promising strategy for the design and synthesis of nDDS for combination chemotherapy.

Keyword:

backboned combination chemotherapy dual drug nanosized drug delivery system polyprodrug

Community:

  • [ 1 ] [Zhang, Honglei]Qilu Univ Technol, Shandong Acad Sci, Sch Chem & Chem Engn, Shandong Prov Key Lab Mol Engn, Jinan 250353, Peoples R China
  • [ 2 ] [Wu, Yanjuan]Qilu Univ Technol, Shandong Acad Sci, Sch Chem & Chem Engn, Shandong Prov Key Lab Mol Engn, Jinan 250353, Peoples R China
  • [ 3 ] [Xue, Xiukun]Qilu Univ Technol, Shandong Acad Sci, Sch Chem & Chem Engn, Shandong Prov Key Lab Mol Engn, Jinan 250353, Peoples R China
  • [ 4 ] [Xu, Ben]Qilu Univ Technol, Shandong Acad Sci, Sch Chem & Chem Engn, Shandong Prov Key Lab Mol Engn, Jinan 250353, Peoples R China
  • [ 5 ] [Li, Tianduo]Qilu Univ Technol, Shandong Acad Sci, Sch Chem & Chem Engn, Shandong Prov Key Lab Mol Engn, Jinan 250353, Peoples R China
  • [ 6 ] [Xu, Xiao]Fuzhou Univ, Inst Food Safety & Environm Monitoring, Coll Chem, Fuzhou 350108, Peoples R China
  • [ 7 ] [Chen, Chen]Fuzhou Univ, Inst Food Safety & Environm Monitoring, Coll Chem, Fuzhou 350108, Peoples R China
  • [ 8 ] [Chen, Zhaowei]Fuzhou Univ, Inst Food Safety & Environm Monitoring, Coll Chem, Fuzhou 350108, Peoples R China

Reprint 's Address:

  • 陈兆委

    [Wu, Yanjuan]Qilu Univ Technol, Shandong Acad Sci, Sch Chem & Chem Engn, Shandong Prov Key Lab Mol Engn, Jinan 250353, Peoples R China;;[Chen, Zhaowei]Fuzhou Univ, Inst Food Safety & Environm Monitoring, Coll Chem, Fuzhou 350108, Peoples R China

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Source :

POLYMERS

ISSN: 2073-4360

Year: 2021

Issue: 1

Volume: 13

4 . 9 6 7

JCR@2021

4 . 7 0 0

JCR@2023

ESI Discipline: CHEMISTRY;

ESI HC Threshold:117

JCR Journal Grade:1

CAS Journal Grade:2

Cited Count:

WoS CC Cited Count: 13

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 0

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