GFP Plasmid and Chemoreagent Conjugated with Graphene Quantum Dots as a Novel Gene Delivery Platform for Colon Cancer Inhibition in Vitro and in Vivo

Pei Ying Lo, Guang Yu Lee, Jia Huei Zheng, Jen Hsien Huang, Er Chieh Cho, Kuen Chan Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Scientists have studied intensively the gene delivery carriers for treating genetic diseases. However, there are challenges that impede the application of naked gene-based therapy at the clinical level, such as quick elimination of the circulation, lack of membrane penetrability, and poor endosome trapping. Herein, we develop graphene quantum dots (GQDs)-derivative nanocarriers and introduce polyethylenimine (PEI) to equip the system with enhanced biocompatibility and abundant functional groups for modification. In addition to carrying green fluorescent protein (GFP) as an example of gene delivery, this system covalently binds colon cancer cells targeted antibody and epidermal growth factor receptor (EGFR) to enhance cell membrane penetrability and cell uptake of nanocarriers. To achieve multistrategy cancer therapy, the anticancer drug doxorubicin (Dox) is noncovalently encapsulated to achieve pH-induced drug release at tumor sites and leaves space for further functional gene modification. This nanoparticle serves as a multifunctional gene delivery system, which facilitates improved cytotoxicity and longer-sustained inhibition capacity compared to free Dox treatments in colon cancer cells. Moreover, our GQD composites display compatible tumor suppression ability compared with the free Dox treatment group in xenograft mice experiment with significantly less toxicity. This GQD nanoplatform was demonstrated as a multifunctional gene delivery system that could contribute to treating other genetic diseases in the future.

Original languageEnglish
Pages (from-to)5948-5956
Number of pages9
JournalACS Applied Bio Materials
Volume3
Issue number9
DOIs
Publication statusPublished - Sep 21 2020

Keywords

  • colon cancer
  • epidermal growth factor receptor (EGFR)
  • gene delivery system
  • graphene quantum dots
  • tumor suppression

ASJC Scopus subject areas

  • Biomaterials
  • Chemistry(all)
  • Biomedical Engineering
  • Biochemistry, medical

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