Photothermal-modulated drug delivery and magnetic relaxation based on collagen/poly(γ-glutamic acid) hydrogel

The design and fabrication of multifunctional hydrogels are important issues in both the pharmaceutical and medical research fields because of their high potential for use in molecular imaging, drug delivery, and tissue... [ view full abstract ]

The design and fabrication of multifunctional hydrogels are important issues in both the pharmaceutical and medical research fields because of their high potential for use in molecular imaging, drug delivery, and tissue engineering. In this study, we developed a novel injectable and photoresponsive composite hydrogel composed of anticancer drugs, imaging contrast agents, bio-derived collagen, and multifaceted anionic polypeptide, poly(γ-glutamic acid) (γ-PGA). By the introduction of γ-PGA, the intrinsic temperature-dependent phase transition behavior of collagen was modified to a low viscous sol state at room temperature and nonflowing gel state around body temperature (ie, injectable hydrogel);. The modified temperature-dependent phase transition behavior of collagen/γ-PGA hydrogels was also evaluated after loading of near-infrared (NIR) fluorophore, indocyanine green (ICG), which could transform absorbed NIR photonic energy into thermal energy. By taking advantage of the abundant carboxylate groups in γ-PGA, cationic-charged doxorubicin (Dox) and hydrophobic MnFe₂O₄ magnetic nanoparticles were also incorporated successfully into the collagen/γ-PGA hydrogels. By illumination of NIR light on the collagen/γ-PGA/Dox/ICG/MnFe₂O₄ hydrogels, the release kinetics of Dox and magnetic relaxation of MnFe₂O₄ nanoparticles could be modulated. The experimental results suggest that the novel injectable and NIR-responsive collagen/γ-PGA hydrogels developed in this study can be used as a theranostic platform after loading of various molecular imaging probes and therapeutic components.