An epirubicin-conjugated nanocarrier with MRI function to overcome lethal multidrug-resistant bladder cancer

Hung Wei Yang, Mu Yi Hua, Hao Li Liu, Rung Ywan Tsai, See Tong Pang, Po Hong Hsu, Hsiang Jun Tang, Tzu Chen Yen, Cheng Keng Chuang

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Multidrug resistance (MDR) presents a major obstacle to curing cancer. Chemotherapy failure can occur through both cell membrane drug resistance (CMDR) and nuclear drug resistance (NDR), and anticancer effectiveness of chemotherapeutic agents is especially reduced by their nuclear export. Here we report an exciting magnetically-targeted nanomedicine formed by conjugation of epirubicin (EPI) to non-toxic and high-magnetization nanocarrier (HMNC). Strikingly, HMNC-EPI overcomes both CMDR and NDR in human bladder cancer cell models, without using P-glycoprotein (P-gp) and nuclear pore inhibitors. Besides, the half-life of drug is prolonged ∼1.8-fold (from 45 h to 81 h) at 37 °C, with a ∼10-fold increase in concentration at the tumor site through magnetic targeting (MT). Moreover, malignant NDR bladder cancer can be effectively inhibited after 14 days in mice by just two injections and MT. We are the first to demonstrate the nanomedical strategy that can overcome the CMDR and NDR bladder cancers simultaneously, and proceed to the excellent MT therapy, significantly reducing the dosage and cardiotoxicity and holding great promise for incurable human MDR bladder cancer.

Original languageEnglish
Pages (from-to)3919-3930
Number of pages12
JournalBiomaterials
Volume33
Issue number15
DOIs
Publication statusPublished - 2012 May

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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