A Novel 89Zr-labeled DDS Device Utilizing Human IgG Variant (scFv): “Lactosome” Nanoparticle-Based Theranostics for PET Imaging and Targeted Therapy

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 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.

Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect

“…At the same time, we observed other types of amphipathic polymer DDSs for BNCT, namely, “A 3 B type Lactosome (A 3 B-Lac)” composed of three hydrophilic PSar and a hydrophobic PLLA. Lim, M et al reported that the A 3 B-Lac conjugated with small interfering RNA (siRNA), having a relatively lower EPR effect on tumor lesions down to 22 nm [ 19 , 55 ]. To overcome the disadvantages and enhance the penetration in tumors, we developed a 27 kDa human single chain variable fragment (scFv) of IgG against the mesothelin (MSLN) overexpressed in various cancer cells [ 56 ].…”

“…The particles are composed of amphipathic polydepsipeptide, which is linked with a hydrophilic polysarcosine (PSar) and a hydrophobic poly-L-lactic acid (PLLA), and this polymer assembly forms micelle-type particles with an average diameter of 36 nm [ 14 , 18 ]. Moreover, the AB-Lac particles show promising prospects for solid tumor accumulation via the enhanced permeability and retention (EPR) effect, which allows particles in the size range 10–100 nm to leak from blood vessels having submicron-sized defects in the tumor lesions where the lymphatic drain system is generally immature [ 19 , 20 ].…”

Nanotheranostics: A powerful next-generation solution to tackle hepatocellular carcinoma

“…Nanotheranostic is a real-time combination of novel therapeutic and modern diagnostic tool or imaging into a single agent linked and integrated by nanoparticles[ 39 , 40 ]. Nanoparticles are the key components of the nanotheranostic agent[ 41 ] which include aptamer[ 42 ], DNA nanostructure[ 43 ], lactosome-based nanoparticles[ 44 ], metallic nanoparticles[ 45 ], gold nanoparticle[ 46 ], silver nanoparticle[ 47 ], dendrimer and copolymer-based nanoparticles[ 48 ], lipid-based nanomaterials[ 49 ], magnetic nanoparticles[ 50 ] iron oxide nanoparticle[ 51 ], mesoporous silica nanoparticle[ 52 ] and quantum dots nanoparticle[ 53 ].…”