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Plant virus-like particles (VLPs) are biocompatible, non-infectious nanomaterials with promising applications as immunotherapeutics and vaccines. However, slow-release VLP formulations are needed to achieve long-term efficacy without repeated administration. VLP hydrogels allow the encapsulation and sustained delivery of VLPs, but the particles must covalently bind the hydrogel polymers to avoid premature loss. This has been achieved so far by in situ VLP polymerization, which requires high viral concentrations (5–10 mg/mL, 0.5–1 wt%) to form stable hybrid VLP–hydrogel networks and this complicates scalability and clinical translation. Here, we developed a novel swell-and-click method that led to successful VLP scaffold formation regardless of the viral load used. As a result, VLP-functionalized hydrogels were fabricated with viral concentrations as low as 0.1–1 mg/mL (0.01–0.1 % wt%) without compromising the scaffold stability on the process. The hydrogels incorporate VLPs during swelling, followed by copper-free click chemistry reactions that bind the particles covalently to the polymer. The swell-and-click method also resulted in more than a two-fold enhancement in VLP uptake into the hydrogels and it provides a means of combined burst release and prolonged sustained release, desired traits for cancer immunotherapy treatment. The present work introduces a novel methodology for the design of VLP-based hydrogels, which could facilitate the scalability of the fabrication process and move a significant step forward towards clinical translation of long-term VLP vaccination in cancer disease.
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This content will become publicly available on July 8, 2026
Copper-Cross-Linked Alginate-Based Hydrogel Nanoparticles for Sustainable Slow-Release Fertilizer Applications
Controlled-release materials are desirable for many delivery applications and have been used to improve the efficiency of fertilizers and pesticides in crop management. Due to their potential to reduce application of toxic chemicals while prolonging exposure to active agents, controlled-release nanomaterials are currently being investigated for increasing agricultural production and preventing overfertilization. Hydrogels are underexplored as controlled-release nanomaterials and can deliver many types of cargo, from metal ions to small molecules. Alginate-based hydrogels are biocompatible and their internal carboxylic acids coordinate agriculturally valuable micronutrients like Cu2+, Zn2+, and Ca2+. Hydrogels comprising ionic and nonionic polymers can coordinate agriculturally valuable micronutrients, and the combination of ionic and nonionic polymers results in hydrogels with tunable release profiles. Alginate, for example, contains carboxylates that ionically cross-link with divalent cations like Cu2+, Zn2+, and Ca2+, while polar moieties on chitin enable nonionic coordination. To our knowledge, soft-material copper-loaded nanoparticles have not yet been applied as controlled-release materials for foliar delivery. In this work, we present the synthesis and micronutrient release characteristics of hydrogel nanoparticles containing Cu2+, which is coordinated by ionic and nonionic polymers. Hydrogel nanoparticles (HNPs) were prepared by liquid–liquid emulsion techniques and cross-linked with Cu2+ to form double-network hydrogels made from alginate and non-cross-linking chitin. Nanoparticles (100–300 nm in diameter) were characterized by cryogenic electron microscopy, nanoparticle tracking analysis, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The copper release profiles of HNPs with different polymer compositions were compared. HNPs containing both chitin and alginate released 8–20 times more copper than HNPs with alginate alone, suggesting that the presence of non-cross-linking polymers improves copper release. Thus, HNP delivery characteristics can be tuned by manipulating intraparticle bond dynamics in the hydrogel polymer matrix.
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- Award ID(s):
- 2001611
- PAR ID:
- 10615082
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- Langmuir
- ISSN:
- 0743-7463
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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