Tumor-specific cytolysis by peptide-conjugated echogenic polymer micelles.

Interest in multifunctional polymer nanoparticles for targeted delivery of anti-cancer drugs has grown significantly in recent years. In this study, tumor-targeting echogenic polymer micelles were prepared from poly(ethylene glycol) methyl ether-alkyl carbonate (mPEG-AC) derivatives, and their potential in cancer therapy was assessed. Various mPEG derivatives with carbonate linkages were synthesized via an alkyl halide reaction between mPEG and alkyl chloroformate. Micelle formation using polymer amphiphiles in aqueous media and the subsequent carbon dioxide (CO2) gas generation from the micelles was confirmed. Their ability to target neuroblastoma was substantially enhanced by incorporating the rabies virus glycoprotein (RVG) peptide. RVG-modified gas-generating micelles significantly inhibited tumor growth in a tumor-bearing mouse model owing to CO2 gas generation within tumor cells and resultant cytolytic effects, showing minimal side effects. The development of multifunctional polymer micelles may offer a promising therapeutic approach for various diseases, including cancer.

Adipocytolytic Polymer Nanoparticles for Localized Fat Reduction.

The demand for body fat reduction is increasing. However, conventional lipolytic approaches fail to control adipose tissue reduction and cause severe side effects in adjacent nonadipose tissues. A strategy to specifically reduce subcutaneous fat using adipocytolytic polymer nanoparticles in a minimally invasive manner is reported here. The polymer nanoparticles are designed to generate carbon dioxide gas when selectively absorbed by adipocytes. The carbon dioxide gas generated within late endosomes/lysosomes induces adipocytolysis, thereby reducing the number of cells. Localized injection of the adipocytolytic nanoparticles substantially reduces subcutaneous fat in a high-fat diet-induced obese mouse model, without significant changes in hematological or serum biochemical parameters. The adipocytolytic efficacy of the nanoparticles is also evaluated in a porcine model. This strategy addresses the need to develop safe and effective adipocytolytic agents using functional polymer nanoparticles.

3D Printing of dynamic tissue scaffold by combining self-healing hydrogel and self-healing ferrogel.

Hydrogels have been widely utilized in tissue engineering applications as functional and biological synthetic extracellular matrices (ECMs) can be created with gels. However, typical hydrogels cannot be exploited in 3D printing, especially in extrusion printing, unless post-cross-linking after printing is provided. Additionally, dynamic tissue scaffolds that can mimic ECM environments in the body have been demonstrated to be useful in tissue engineering. Here, we hypothesized that a 3D-printed dynamic tissue scaffold could be fabricated by combining self-healing hydrogel and self-healing ferrogel without post-cross-linking, which could be useful for the regulation of cell phenotype under magnetic stimulation. Hydrogels were formed from oxidized sodium hyaluronate and glycol chitosan, and adipic acid dihydrazide was additionally utilized for self-healing behavior of the gel. Superparamagnetic iron oxide nanoparticles (SPIONs) were also used to prepare a magnetically responsive hydrogel system (i.e., ferrogel). Physicochemical properties, cytotoxicity, and printability of the self-healing hydrogel/ferrogel system fabricated by a 3D printing process, were investigated. Dimensional changes in a tissue scaffold were achieved by the application of a magnetic field. Interestingly, chondrogenic differentiation of ATDC5 cells cultured within the dynamic tissue scaffold was enhanced by applying a magnetic field in vitro. This approach may be useful for fabricating dynamic tissue scaffolds by a 3D printing method for tissue engineering applications.

3D printing of self-healing ferrogel prepared from glycol chitosan, oxidized hyaluronate, and iron oxide nanoparticles.

Hydrogel systems that show self-healing ability after mechanical damage are receiving increasing attention. However, self-healing hydrogels suitable for biomedical applications are limited owing to complex preparation methods. Furthermore, few studies have demonstrated the self-healing property of ferrogels. In this study, we demonstrated that glycol chitosan (GC) and oxidized hyaluronate (OHA) can be used to form a self-healing ferrogel in the presence of superparamagnetic iron oxide nanoparticles (SPIONs) without additional chemical cross-linkers. The overall characteristics of GC/OHA/SPION ferrogel varied based on the GC/OHA ratio, SPION content, and total polymer concentration. Interestingly, GC/OHA/SPION ferrogel was used to fabricate 3D-printed constructs of various shapes via an extrusion printing method. These constructs were responsive to the magnetic field, suggesting their potential application in 4D printing. This approach to developing self-healing ferrogels with biocompatible polysaccharides may prove useful in designing and fabricating drug delivery systems and tissue engineering scaffolds, via 3D printing.