Furin-mediated intracellular self-assembly of olsalazine nanoparticles for enhanced magnetic resonance imaging and tumour therapy

Yue Yuan, Jia Zhang, Xiaoliang Qi, Shuoguo Li, Guanshu Liu, Soumik Siddhanta, Ishan Barman, Xiaolei Song, Michael T. McMahon, Jeff W.M. Bulte

Research output: Contribution to journalArticle

Abstract

Among the strategies used for enhancement of tumour retention of imaging agents or anticancer drugs is the rational design of probes that undergo a tumour-specific enzymatic reaction preventing them from being pumped out of the cell. Here, the anticancer agent olsalazine (Olsa) was conjugated to the cell-penetrating peptide RVRR. Taking advantage of a biologically compatible condensation reaction, single Olsa-RVRR molecules were self-assembled into large intracellular nanoparticles by the tumour-associated enzyme furin. Both Olsa-RVRR and Olsa nanoparticles were readily detected with chemical exchange saturation transfer magnetic resonance imaging by virtue of exchangeable Olsa hydroxyl protons. In vivo studies using HCT116 and LoVo murine xenografts showed that the OlsaCEST signal and anti-tumour therapeutic effect were 6.5- and 5.2-fold increased, respectively, compared to Olsa without RVRR, with an excellent ‘theranostic correlation’ (R2 = 0.97) between the imaging signal and therapeutic response (normalized tumour size). This furin-targeted, magnetic resonance imaging-detectable platform has potential for imaging tumour aggressiveness, drug accumulation and therapeutic response.

Original languageEnglish (US)
JournalNature Materials
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Furin
Magnetic resonance
Self assembly
magnetic resonance
self assembly
Tumors
therapy
tumors
Nanoparticles
Imaging techniques
nanoparticles
drugs
Cell-Penetrating Peptides
Condensation reactions
cells
Heterografts
Pharmaceutical Preparations
Hydroxyl Radical
Antineoplastic Agents
Peptides

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

Cite this

Furin-mediated intracellular self-assembly of olsalazine nanoparticles for enhanced magnetic resonance imaging and tumour therapy. / Yuan, Yue; Zhang, Jia; Qi, Xiaoliang; Li, Shuoguo; Liu, Guanshu; Siddhanta, Soumik; Barman, Ishan; Song, Xiaolei; McMahon, Michael T.; Bulte, Jeff W.M.

In: Nature Materials, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Liu, Guanshu

AU - Siddhanta, Soumik

AU - Barman, Ishan

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AU - McMahon, Michael T.

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