Reduction-Responsive Codelivery System Based on a Metal-Organic Framework for Eliciting Potent Cellular Immune Response

Yong Yang, Qanqian Chen, Jian-Ping Wu, Thomas Brett Kirk, Jiake Xu, Zonghua Liu, Wei Xue

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Utilizing nanopartides to deliver subunit vaccines can be viewed as a promising strategy for enhancing the immune response, especially with regard to cellular immunity to fight against infectious viruses and malignant cancer. Nevertheless, its applications are still far from practicality because of some limitations such as high cost, non-biocompatibility, non-biodegradability, and the inefficient stimulation of cytotoxic T lymphocyte (CTL) response. In this study, we use metal-organic framework (MOF) MIL-101-Fe-NH2 nanoparticles as carriers to fabricate an innovative reduction-responsive antigen delivery system for cotransporting the antigen model ovalbumin (OVA) and an immune adjuvant, unmethylated cytosine-phosphate guanine (CpG) oligonucleotide. In vitro cellular tests show that the MOF nanopartides can not only greatly improve the uptake of OVA by the antigen-presenting cells but also smartly deliver both OVA and CpG into the same cell. By feat of the reductively controllable release of OVA and the promoting function of CpG, the delivery system can elicit strong cellular immunity and CTL response in mice. Moreover, the increased frequencies of effector memory T cells inspired by the delivery system indicate that it can induce a potent immune memory response. These results demonstrate that MOF nanoparticles are excellent vehicles for codelivering antigen and immune adjuvant and may find wider applications in biomedical fields.

Original languageEnglish
Pages (from-to)12463-12473
Number of pages11
JournalACS applied materials & interfaces
Volume10
Issue number15
DOIs
Publication statusPublished - 18 Apr 2018

Keywords

  • ANTIGEN-DELIVERY-SYSTEM
  • ANTITUMOR RESPONSES
  • CANCER-IMMUNOTHERAPY
  • DESIGN
  • DRUG-DELIVERY
  • IMMUNOSTIMULATORY OLIGONUCLEOTIDES
  • NANOGELS
  • NANOPARTICLE VACCINES
  • PLATFORMS
  • antigen delivery
  • cellular immunity
  • cytotoxic T lymphocyte
  • metal-organic framework
  • reduction-responsive

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