Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Dec 16;14(12):2832.
doi: 10.3390/pharmaceutics14122832.

Recent Advances in the Biomedical Applications of Functionalized Nanogels

Kannan Badri Narayanan  1   2 , Rakesh Bhaskar  1 , Sung Soo Han  1   2
Affiliations
Review

Recent Advances in the Biomedical Applications of Functionalized Nanogels

Kannan Badri Narayanan et al. Pharmaceutics. .

Abstract

Nanomaterials have been extensively used in several applications in the past few decades related to biomedicine and healthcare. Among them, nanogels (NGs) have emerged as an important nanoplatform with the properties of both hydrogels and nanoparticles for the controlled/sustained delivery of chemo drugs, nucleic acids, or other bioactive molecules for therapeutic or diagnostic purposes. In the recent past, significant research efforts have been invested in synthesizing NGs through various synthetic methodologies such as free radical polymerization, reversible addition-fragmentation chain-transfer method (RAFT) and atom transfer radical polymerization (ATRP), as well as emulsion techniques. With further polymeric functionalizations using activated esters, thiol-ene/yne processes, imines/oximes formation, cycloadditions, nucleophilic addition reactions of isocyanates, ring-opening, and multicomponent reactions were used to obtain functionalized NGs for targeted delivery of drug and other compounds. NGs are particularly intriguing for use in the areas of diagnosis, analytics, and biomedicine due to their nanodimensionality, material characteristics, physiological stability, tunable multi-functionality, and biocompatibility. Numerous NGs with a wide range of functionalities and various external/internal stimuli-responsive modalities have been possible with novel synthetic reliable methodologies. Such continuous development of innovative, intelligent materials with novel characteristics is crucial for nanomedicine for next-generation biomedical applications. This paper reviews the synthesis and various functionalization strategies of NGs with a focus on the recent advances in different biomedical applications of these surface modified/functionalized single-/dual-/multi-responsive NGs, with various active targeting moieties, in the fields of cancer theranostics, immunotherapy, antimicrobial/antiviral, antigen presentation for the vaccine, sensing, wound healing, thrombolysis, tissue engineering, and regenerative medicine.

Keywords: cancer; functionalization; nanogel; polymers; stimuli-responsive; targeted delivery; theranostics.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Various functionalization strategies involved in the synthesis of functionalized NGs.
Figure 2
Figure 2
Surface modifications of NGs with various chemical/biological moieties for biomedical applications.
Figure 3
Figure 3
An aptamer-modified DNA tetrahedron-based NG for combined chemo/gene therapy of MDR tumors. Reproduced from Tang et al. [111] with permission from American Chemical Society, USA.
Figure 4
Figure 4
Characterization of TLR7/8-agonist- and protein-conjugated NGs for precise co-delivery of adjuvant and antigen during intravenous antitumor vaccination. (A) Synthetic design concept based on double reactive precursor block copolymers that self-assemble into block copolymer micelles with amine-reactive cores and a SPAAC-reactive corona. Using aminolysis of the pentafluorophenyl esters, the cores are covalently functionalized with the TLR 7/8 agonist IMDQ and Texas Red, and then sequentially cross-linked and transformed into pH-responsive NGs. The corona is modified via click ligation of the surface-exposed azides to DBCO-modified (and Alexa Fluor 488-labeled) OVA as a model antigen. (B) Size exclusion chromatography of the RAFT-derived reactive homo and block copolymer (before and after removal of the dithiobenzoate end group). (C) Dynamic light scattering intensity size distribution plots of the resulting NGs (with and without covalent IMDQ loading), mixed or covalently modified with OVA. (D) SDS-PAGE of modified OVA (labeled with Alexa Fluor 488) mixed or covalently conjugated to IMDQ-loaded NGs (labeled with Texas Red) (left, Coomassie staining; right, UV excitation of the fluorescent dyes (red, Texas Red-labeled NG; green, Alex Fluor 488-labeled OVA)). (E) UV–vis spectrum of the fluorescently labeled samples and (F) corresponding image of the samples upon excitation by a UV lamp. Reproduced from Stickdorn et al. [143] with permission from American Chemical Society, USA.
Figure 5
Figure 5
(A) The schematic diagram for the loading of the Carbopol Aqua SF1 NG with an antibiotic (ABX+) (ABX = ciprofloxacin) followed by surface coating with protease (Alcalase 2.4 L FG). (B) Diagram of the mechanism of action of the Carbopol Aqua SF1–Alcalase 2.4 L FG NG particles on biofilms adhered to a substrate. Reproduced from Weldrick et al. [165] with permission from American Chemical Society, USA.
Figure 6
Figure 6
Intra-articular injection of NGs slows down cartilage degeneration in anterior cruciate ligament transection osteoarthritis (ACLT) induced rat osteoarthritis model. (A) Macroscopic appearance of cartilage from tibial plateaus, (B) H&E staining of knee joints, (C) Safranin O/Fast Green stained sections of knee joints, (D) The macroscopic observation scores of knee joints, (E) Cartilage degeneration evaluated with the Osteoarthritis Research Society International (OARSI) scoring system. (* p < 0.05, ** p < 0.01 and *** p < 0.001). Reproduced from Li et al. [180] with permission from Elsevier.
Figure 7
Figure 7
Both urokinase (UK) and PEG-UK reduced neurological deficits. (A) The clinical scores. (B) Representative images of the threshold of toxicological concern (TTC) straining and diffusion-weighted imaging (DWI) in each group: the infarcted part stained white, whereas the normal part-stained red. (C) The mean relative infarction volume of each group. ** p < 0.01 vs. pMCAO; ## p < 0.01 vs. UK. Reproduced from Cui et al. [214] with permission from Elsevier.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Patra J.K., Das G., Fraceto L.F., Campos E.V.R., Rodriguez-Torres M.d.P., Acosta-Torres L.S., Diaz-Torres L.A., Grillo R., Swamy M.K., Sharma S., et al. Nano based drug delivery systems: Recent developments and future prospects. J. Nanobiotechnol. 2018;16:71. doi: 10.1186/s12951-018-0392-8. - DOI - PMC - PubMed
    1. Cho H., Jammalamadaka U., Tappa K. Nanogels for pharmaceutical and biomedical applications and their fabrication using 3D printing technologies. Materials. 2018;11:302. doi: 10.3390/ma11020302. - DOI - PMC - PubMed
    1. Mauri E., Papa S., Masi M., Veglianese P., Rossi F. Novel functionalization strategies to improve drug delivery from polymers. Expert Opin. Drug Deliv. 2017;14:1305–1313. doi: 10.1080/17425247.2017.1285280. - DOI - PubMed
    1. Keskin D., Zu G., Forson A.M., Tromp L., Sjollema J., van Rijn P. Nanogels: A novel approach in antimicrobial delivery systems and antimicrobial coatings. Bioact. Mater. 2021;6:3634–3657. doi: 10.1016/j.bioactmat.2021.03.004. - DOI - PMC - PubMed
    1. Preman N.K., Jain S., Johnson R.P. “Smart” Polymer nanogels as pharmaceutical carriers: A versatile platform for programmed delivery and diagnostics. ACS Omega. 2021;6:5075–5090. doi: 10.1021/acsomega.0c05276. - DOI - PMC - PubMed

LinkOut - more resources