A novel89zr-labeled dds device utilizing human igg variant (Scfv): “lactosome” nanoparticle-based theranostics for pet imaging and targeted therapy

Melissa Siaw Han Lim, Takashi Ohtsuki, Fumiaki Takenaka, Kazuko Kobayashi, Masaru Akehi, Hirotaka Uji, Hirotsugu Kobuchi, Takanori Sasaki, Eiichi Ozeki, Eiji Matsuura

Research output: Contribution to journalReview articlepeer-review

Abstract

“Theranostics,” a new concept of medical advances featuring a fusion of therapeutic and diagnostic systems, provides promising prospects in personalized medicine, especially cancer. The theranostics system comprises a novel89Zr-labeled drug delivery system (DDS), derived from the novel biodegradable polymeric micelle, “Lactosome” nanoparticles conjugated with specific short-ened IgG variant, and aims to successfully deliver therapeutically effective molecules, such as the apoptosis-inducing small interfering RNA (siRNA) intracellularly while offering simultaneous tumor visualization via PET imaging. A 27 kDa-human single chain variable fragment (scFv) of IgG to establish clinically applicable PET imaging and theranostics in cancer medicine was fabricated to target mesothelin (MSLN), a 40 kDa-differentiation-related cell surface glycoprotein antigen, which is frequently and highly expressed by malignant tumors. This system coupled with the cell penetrating peptide (CPP)-modified and photosensitizer (e.g., 5, 10, 15, 20-tetrakis (4-aminophenyl) por-phyrin (TPP))-loaded Lactosome particles for photochemical internalized (PCI) driven intracellular siRNA delivery and the combination of 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) offers a promising nano-theranostic-based cancer therapy via its targeted apoptosis-inducing fea-ture. This review focuses on the combined advances in nanotechnology and material sciences utilizing the “89Zr-labeled CPP and TPP-loaded Lactosome particles” and future directions based on important milestones and recent developments in this platform.

Original languageEnglish
Article number158
Pages (from-to)1-29
Number of pages29
JournalLife
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 2021

Keywords

  • ATP-binding cassette subfamily G member 2 (ABCG2)
  • Accelerated blood clearance (ABC)
  • Cell penetrating peptide (CPP)
  • Drug delivery system (DDS)
  • PET imaging
  • Photodynamic therapy (PDT)
  • SiRNA
  • Single chain variable fragment of IgG (scFv)
  • Theranostics

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Space and Planetary Science
  • Palaeontology

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