A Novel <sup>89</sup>Zr-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
Affiliations
Melissa Siaw Han Lim
Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
Takashi Ohtsuki
Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, Japan
Fumiaki Takenaka
Collaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
Kazuko Kobayashi
Collaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
Masaru Akehi
Collaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
Hirotaka Uji
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
Hirotsugu Kobuchi
Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
Takanori Sasaki
Collaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
Eiichi Ozeki
Technology Research Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan
Eiji Matsuura
Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
“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 novel 89Zr-labeled drug delivery system (DDS), derived from the novel biodegradable polymeric micelle, “Lactosome” nanoparticles conjugated with specific shortened 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) porphyrin (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 feature. 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.
