Mitochondria-Targeting Polydopamine Nanoparticles to Deliver Doxorubicin for Overcoming Drug Resistance

Wen Qing Li, Zhigang Wang, Sijie Hao, Hongzhang He, Yuan Wan, Chuandong Zhu, Li Ping Sun, Gong Cheng, Si Yang Zheng

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

Mitochondria play a critical role in diverse cellular processes, such as energy production and apoptosis regulation. The mitochondria-targeted drug delivery is becoming a potential novel strategy for overcoming drug resistance in cancer therapy. Herein, we synthesize nature-inspired dopamine-derived polydopamine (PDA) nanoparticles. Using triphenylphosphonium (TPP) as the mitochondrial penetration molecule to improve the target efficiency, we synthesize poly(ethylene glycol) (PEG)-modified PDA (PDA-PEG) and TPP-functionalized PEG-modified PDA (PDA-PEG-TPP) nanoparticles. Then anticancer drug doxorubicin (DOX) was loaded on PDA-PEG and PDA-PEG-TPP (PDA-PEG-DOX and PDA-PEG-TPP-DOX) nanoparticles, which are apt to deliver DOX to cell nuclei and mitochondria, respectively. To mimic the repeated anticancer drug treatment in clinical cases, we repeatedly treated the MDA-MD-231 cancer cells for a long time using DOX-loaded nanoparticles and find that the mitochondria targeting PDA-PEG-TPP-DOX has higher potential to overcome the drug resistance than the regular delivery nanoparticles PDA-PEG-DOX. These results indicate the promising potential of applying PDA-PEG-TPP-DOX nanoparticles in mitochondria-targeted drug delivery to overcome the drug resistance in long-time anticancer chemotherapy.

Original languageEnglish (US)
Pages (from-to)16793-16802
Number of pages10
JournalACS Applied Materials and Interfaces
Volume9
Issue number20
DOIs
StatePublished - May 24 2017

All Science Journal Classification (ASJC) codes

  • General Materials Science

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