Nanoparticle-hydrogel superstructures for biomedical applications

Abstract

The incorporation of nanoparticles into hydrogels yields novel superstructures that have become increasingly popular in biomedical research. Each component of these nanoparticle-hydrogel superstructures can be easily modified, resulting in platforms that are highly tunable and inherently multifunctional. The advantages of the nanoparticle and hydrogel constituents can be synergistically combined, enabling these superstructures to excel in scenarios where employing each component separately may have suboptimal outcomes. In this review, the synthesis and fabrication of different nanoparticle-hydrogel superstructures are discussed, followed by an overview of their use in a range of applications, including drug delivery, detoxification, immune modulation, and tissue engineering. Overall, these platforms hold significant clinical potential, and it is envisioned that future development along these lines will lead to unique solutions for addressing areas of pressing medical need.

Keywords: Detoxification; Drug delivery; Hydrogel hybrid; Immune modulation; Nanomedicine; Nanoparticle; Tissue engineering.

Fig. 1.

Nanoparticle–hydrogel superstructures for biomedical applications. Nanoparticle–hydrogel systems combine the unique advantages of their constituent components, which has enabled them to excel in applications such as drug delivery, immune modulation, detoxification, and tissue engineering.

Fig. 2.

Stimuli-responsive polyacrylamide hydrogel-coated MOF nanoparticles. (A) MOF nanoparticles are modified with nucleic acids and loaded with drugs. The nanoparticles can then be coated with DNA-functionalized acrylamide polymers. Upon incubation with ATP, triggered release can be achieved. (B) Tumor spheroids treated with (a) unloaded hydrogel-coated MOF nanoparticles, (b) uncoated MOF nanoparticles, or (c) the hydrogel-coated MOF nanoparticles and the corresponding cytotoxicity in spheroids. Adapted with permission [34]. Copyright 2017, WILEY-VCH.

Fig. 3.

Light-inducible hydrogels based on mesoporous silica nanoparticles. (A) Mesoporous silica nanoparticles functionalized with an azobenzene group and α-cyclodextrin can form a hydrogel structure when exposed to NIR irradiation. When subjected to hyaluronidase (Hase) treatment, the hydrogel dissociates. (B) Scanning electron microscopy (a-c), optical microscopy (d-f), and fluorescence microscopy (g-i) demonstrate coating of tumor spheroids with the mesoporous silica nanoparticle-based hydrogel. The middle and right columns show higher magnification images of the hydrogel and cell sections, respectively. Adapted with permission [109]. Copyright 2016, American Chemical Society.

Fig. 4.

Oral delivery of Fab′ -functionalized nanoparticles coated with hydrogels. (A) When the nanoparticle (NP)-embedded hydrogels reach the colon, the nanoparticles are released and can be internalized by tumor cells. (B) Coumarin 6-loaded nanoparticles (CM-NPs) are taken up significantly more by tumor tissue when functionalized with Fab’. Adapted with permission [128]. Copyright 2018, American Chemical Society

Fig. 5.

Thermoresponsive polydopamine nanoparticle-knotted PEG hydrogel. (A) The nanoparticle–hydrogel network can be incorporated with SN38, a chemotherapeutic, by π−π stacking. The drug can then be released upon NIR irradiation. (B) Absorbance profiles confirm successful loading of hydrogels with different amounts of SN38. (C) Drug release can be modulated in an on-demand manner upon NIR irradiation. (D) The nanoparticle–hydrogel formulation can significantly increase tumor-site temperature upon NIR irradiation. Adapted with permission [54]. Copyright 2017, American Chemical Society.

Fig. 6.

Hydrogels loaded with cell membrane-coated nanoparticles for toxin neutralization. (A) Hydrogels are formulated with red blood cell (RBC) membrane-coated nanosponges (NS) that are capable of binding and neutralizing pore-forming toxins. (B) NS are better retained within the hydrogel when a higher concentration of crosslinker is used. (C) Scanning electron microscopy is used to visualize the NS–hydrogel structure. (D) NS incorporated within the hydrogels retain at the injection site better than free NS. Adapted with permission [134]. Copyright 2015, WILEY- VCH.

Fig. 7.

Colloidal hydrogel with cell membrane-coated nanoparticles for toxin neutralization. (A) The nanosponge colloidal (NC) gels are formed by the electrostatic interaction between negatively charged RBC-NPs and chitosan-coated nanoparticles (Chi-NPs). (B) Macroscopic images demonstrate the structure of the NC gel. (C) Fluorescent imaging shows that the NC gels are formed by a network of RBC-NPs (red) and Chi-NPs (green). (D) When incorporated into NC gels, RBC-NPs retain better at the site of injection. Adapted with permission [59]. Copyright 2017, American Chemical Society.

Fig. 8.

Porous hydrogels containing protein-conjugated gold nanoparticles for immune modulation. (A) A porous alginate gel functionalized with a diabetes-relevant BDC peptide is incorporated with GM-CSF-conjugated gold nanoparticles. (B) The peptide, which is fluorescently labeled and contains a matrix metallopeptidase-cleavable sequence, is linked to the alginate via a PEG tether. (C) When administered subcutaneously, the hydrogel containing GM-CSF-conjugated gold nanoparticles exhibits significantly higher metallopeptidase activity. Adapted with permission [150]. Copyright 2017, WILEY-VCH.

Fig. 9.

Carbon nanotube (CNT)-embedded hydrogel sheets for cardiac scaffolds. (A) CNT bundles are coated with GelMA and crosslinked to form fractal-like networks. (B) With increasing amounts of CNT, the hydrogels become increasingly conductive. (C) A more uniform distribution of cardiomyocytes is seen when the cells are cultured onto CNT-incorporated hydrogels. Adapted with permission [63]. Copyright 2013, American Chemical Society.