Mannose-conjugated layered double hydroxide nanocomposite for targeted siRNA delivery to enhance cancer therapy

Nanomedicine. 2018 Oct;14(7):2355-2364. doi: 10.1016/j.nano.2017.06.006. Epub 2017 Jun 22.

Abstract

Sheet-like layered double hydroxide nanoparticles (LDH NPs) have showed great potentials in biomedical applications such as nanocarriers for drug and gene delivery, biosensors and imaging agents. However, target delivery of drugs and genes using LDH NPs to the desired tumor sites is a major challenge in cancer therapy. The aim of this study is to develop a functional LDH-based nanocomposite for target delivery of siRNA to cancer cells. Mannose as a targeting moiety was firstly conjugated onto SiO2-coated LDH nanocomposite. Cellular uptake data have demonstrated that siRNA is more efficiently delivered to osteosarcoma (U2OS) cells by mannose-conjugated SiO2 coated LDH nanocomposite (Man-SiO2@LDH) compared to unmodified LDH NP. A commercial cell death-siRNA (CD-siRNA) delivered by Man-SiO2@LDH can kill cancer cells more effectively. These results reveal that the Man-SiO2@LDH nanocomposite is capable of target-delivering siRNA or drugs to tumor cells for more effective cancer treatment, which provides great potentials in cancer therapy.

Keywords: Hierarchical nanocomposites; Layered double hydroxide nanoparticles; Mannose-directed target delivery; siRNA therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Bone Neoplasms / therapy*
  • Cell Death
  • Drug Delivery Systems*
  • Humans
  • Hydroxides / chemistry*
  • Mannose / chemistry*
  • Nanocomposites / administration & dosage*
  • Nanocomposites / chemistry
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology
  • Osteosarcoma / therapy*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics
  • Tumor Cells, Cultured

Substances

  • Hydroxides
  • RNA, Small Interfering
  • hydroxide ion
  • Mannose