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International journal of nanomedicine
2022;17 1323-1341.

Two-Pronged Anti-Tumor Therapy by a New Polymer-Paclitaxel Conjugate Micelle with an Anti-Multidrug Resistance Effect.

Juan Du, Lanlan Zong, Mengmeng Li, Keke Yu, Yonghui Qiao, Qi Yuan, Xiaohui Pu
Author Information
  1. Juan Du: Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People's Republic of China.
  2. Lanlan Zong: Institute of Pharmacy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People's Republic of China.
  3. Mengmeng Li: Institute of Pharmacy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People's Republic of China.
  4. Keke Yu: Institute of Pharmacy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People's Republic of China.
  5. Yonghui Qiao: Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People's Republic of China.
  6. Qi Yuan: Institute of Pharmacy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People's Republic of China.
  7. Xiaohui Pu: Institute of Pharmacy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People's Republic of China.
PMID: 35345783 DOI: 10.2147/IJN.S348598

Abstract

Introduction: Cancerous tumors are still a major disease that threatens human life, with tumor multidrug resistance (MDR) being one of the main reasons for the failure of chemotherapy. Thus, reversing tumor MDR has become a research focus of medical scientists.
Methods: Here, a reduction-sensitive polymer prodrug micelle, mPEG-DCA-SS-PTX (PDSP), was manufactured with a new polymer inhibitor of drug resistance as a carrier to overcome MDR and improve the anti-tumor effect of PTX.
Results: The PDSP micelles display good stability, double-responsive drug release, and excellent biocompatibility. The PDSP micelles reduced the cytotoxicity of PTX to normal HL-7702 cells and enhanced that to SMMC-7721 and MCF-7 cells in vitro. Improved sensitivity of A549/ADR to PDSP was also observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of PTX to H22 subcutaneous tumor-bearing mice.
Conclusion: This work proves that the reduction-sensitive polymer prodrug micelles carried by the new polymer inhibitor can be used as an alternative delivery system to target tumors and reverse MDR for paclitaxel and other tumor-resistant drugs.

Keywords

anti-multidrug resistance liver targeting paclitaxel polymer prodrug micelles reduction sensitivity

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MeSH Term

Animals
Drug Delivery Systems
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Humans
Mice
Micelles
Paclitaxel
Polymers

Chemicals

Micelles
Polymers
Paclitaxel
Journal Article

Word Cloud

Created with Highcharts 10.0.0polymerMDRPDSPmicellesresistanceprodrugPTXtumorstumorreduction-sensitivenewinhibitordrugreducedcellsenhancedvitrosensitivitypaclitaxelIntroduction:CancerousstillmajordiseasethreatenshumanlifemultidrugonemainreasonsfailurechemotherapyThusreversingbecomeresearchfocusmedicalscientistsMethods:micellemPEG-DCA-SS-PTXmanufacturedcarrierovercomeimproveanti-tumoreffectResults:displaygoodstabilitydouble-responsivereleaseexcellentbiocompatibilitycytotoxicitynormalHL-7702SMMC-7721MCF-7ImprovedA549/ADRalsoobservedFurthermorevivoexperimentsshowsystemictoxicitytherapeuticefficacyH22subcutaneoustumor-bearingmiceConclusion:workprovescarriedcanusedalternativedeliverysystemtargetreversetumor-resistantdrugsTwo-ProngedAnti-TumorTherapyNewPolymer-PaclitaxelConjugateMicelleAnti-MultidrugResistanceEffectanti-multidruglivertargetingreduction

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