Enhanced delivery of the phototherapeutic nanoparticles via hepatocyte overload.

Phototherapeutic nanoparticles (NPs) were prepared with methylene blue (MB), indocyanine green (ICG), and Solutol through self-assembly. Generation of reactive oxygen species and elevation of temperature were observed that verify the photodynamic/photothermal effects of the NPs. Morphology and size distribution of the NPs were examined by transmittance electron microscopy and dynamic light scattering. The biodistribution of the NPs and their antitumor efficacy were examined using tumor-bearing mice to understand the phototherapeutic effect of the NPs on tumors. To enhance targetability with enhanced therapeutic efficacy, empty NPs (Solutol nanoparticles without MB and ICG) at different concentrations were injected along with the phototherapeutic NPs. Enhanced delivery of the phototherapeutic NPs at the tumor site was examined based on hepatocyte overload.

Pluronics: Intelligent building units for targeted cancer therapy and molecular imaging.

Pluronics are triblock copolymers, in which two hydrophilic poly (ethylene oxide) (PEO) blocks are connected via a hydrophobic poly propylene oxide (PPO) block. Because of their low molecular weight and high content of PEO, Pluronics have demonstrated the micellization phenomenon, which is dependent on temperature and/or concentration. With an understanding of micellization phenomenon in more detail, information on the morphology, micelle core radius, aggregation behavior with critical micelle concentration (CMC) and critical micelle temperature (CMT) and so on has been revealed. Based on this acquired information, various studies have been performed for biomedical applications such as drug delivery systems, tissue regeneration scaffolders, and biosurfactants. This review discusses the delivery of small molecules and macromolecules using Pluronic-based NPs and their composites.

The multilayer nanoparticles for deep penetration of docetaxel into tumor parenchyma to overcome tumor microenvironment.

Deep penetration of the anticancer drug, docetaxel (DTX), into tumor parenchyma was demonstrated to achieve improved chemotherapy. For this purpose, a multistage nanostructure was designed and characterized using the multilayer nanoparticles (NPs). The multilayer NPs had a core/shell structure. The core was composed of the DTX-loaded Pluronic NPs (diameter: 12nm) that were transferred into the inner side of vesicles to form the vesicle NPs. Förster resonance energy transfer (FRET) in the NPs was observed to verify the incorporation of the DTX-loaded Pluronic NPs into the inner side of the vesicles during the formation of the vesicle NPs. Subsequently, the vesicle NPs were stabilized through Pluronic-lipid bilayer interaction to form the multilayer NPs. To examine the morphology and size distribution of the multilayer NPs, transmittance electron microscopy and dynamic light scattering were used. In vitro release behavior and toxicity were observed to verify the functionality of the multilayer NPs as nanocarriers for cancer therapy. Multistage functionality was evaluated by cellular uptake and tissue distribution behaviors of the multilayer NPs. The biodistribution of the multilayer NPs and their antitumor efficacy were also observed to understand the role of multistage functionality for improved chemotherapy.

Doxorubicin/heparin composite nanoparticles for caspase-activated prodrug chemotherapy.

Caspase-activated prodrug chemotherapy is introduced and demonstrated using the composite nanoparticles (NPs), which deliver doxorubicin (DOX) and DEVD-S-DOX together to the tumor tissue. DEVD-S-DOX, DOX linked to a peptide moiety (DEVD), is a prodrug that is cleaved into free DOX by caspase-3 upon apoptosis. DEVD-S-DOX has no therapeutic efficacy, but it changes into free DOX with the expression of caspase-3. With the accumulation of the composite NPs in the tumor tissue by the enhanced permeation and retention (EPR) effect, a small exposure of DOX in the tumor cells initiated apoptosis in a localized area of the tumor tissue, which induced caspase-3 activation. Cleavage of DEVD-S-DOX into free DOX by caspase-3 continued with repetitive activation of caspase-3 and cleavage of DEVD-S-DOX at the tumor site. The composite NPs were characterized with transmittance electron microscopy (TEM) and particle size analyzer. We then evaluated the nanoparticle drug release, therapeutic efficacy, and in vivo biodistribution for tumor targeting using a non-invasive live animal imaging technology and the quantification of DOX with high performance liquid chromatography. DOX-induced apoptosis-targeted chemotherapy (DIATC) was verified by in vitro/in vivo DEVD-S-DOX response to free DOX and cellular uptake behavior of the composite NPs with flow cytometry analysis. Significant antitumor efficacy with minimal cardiotoxicity was also observed, which supported DIATC for improved chemotherapy.

Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy.

A mixture of docetaxel (DTX) and Solutol(®) HS 15 (Solutol) transiently formed nanodroplets when it was suspended in an aqueous medium. However, nanodroplets that comprised DTX and Solutol showed a rapid precipitation of DTX because of their unstable characteristics in the aqueous medium. The incorporation of nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent stabilization was designed to prepare multilayer nanoparticles (NPs) with a DTX-loaded Solutol nanodroplet (as template NPs) core for an efficient delivery of DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets (~11.7 nm) were observed to have an increased average diameter (from 11.7 nm to 156.1 nm) and a good stability of the hydrated NPs without precipitation of DTX by vesicle fusion and multilayered structure, respectively. Also, a long circulation of the multilayer NPs was observed, and this was due to the presence of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved antitumor efficacy based on the enhanced permeation and retention effect. Therefore, this study indicated that the multilayer NPs have a considerable potential as a drug delivery system with an enhanced therapeutic efficacy by blood circulation and with low side effects.

Doxorubicin/gold-loaded core/shell nanoparticles for combination therapy to treat cancer through the enhanced tumor targeting.

A combination therapy consisting of radiotherapy and chemotherapy is performed using the core/shell nanoparticles (NPs) containing gold NPs and doxorubicin (DOX). Gold NPs in the core/shell NPs were utilized as a radiosensitizer. To examine the morphology and size distribution of the core/shell NPs, transmittance electron microscopy and dynamic light scattering were used. The in vitro release behavior, cellular uptake and toxicity were also observed to verify the functionality of the core/shell NPs as a nanocarrier. To demonstrate the advantage of the core/shell NPs over traditional gold NPs reported in the combination therapy, we evaluated the accumulation behavior of the core/shell NPs at the tumor site using the biodistribution. Antitumor efficacy was observed with and without radiation to evaluate the role of gold NPs as a radiosensitizer.