Clickable modular polysaccharide nanoparticles for selective cell-targeting

• Published in: Carbohydrate polymers 2020-04, Vol.234, p.115901-115901, Article 115901
• Main Authors: Peuler, Kevin, Dimmitt, Nathan, Lin, Chien-Chi
• Format: Article
• Language: English
• Subjects: Cell targeting; Dextran; Heparin; Nanoparticles; Norbornene-tetrazine reaction
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2020.115901

•Methods for fabricating layered polysaccharide nanoparticles were developed.•Clickable handle was installed on the surface using heparin-tetrazine.•Clickable PEGylation was demonstrated via using norbornene-modified PEG.•Uptake of nanoparticles were demonstrated with monocytes/macrophages fibroblasts.•Layered polysaccharide nanoparticles were used as a drug carrier. A therapeutic nanocarrier capable of cell targeting has the potential to reduce off-target effects of otherwise effective drugs. Nanoparticle surface modification can be tailored for specific cells, however multistep surface modification can prove slow and difficult for a variety of cell types. Here, we designed drug carrying polysaccharide based nanoparticles with a layered structure for clickable surface modification. The center of nanoparticle was composed of cationic macromer (e.g., poly-l-lysine) and anionic polysaccharide (e.g., heparin). Furthermore, a ‘clickable’ polysaccharide was installed on the surface of the nanoparticles to permit a wide range of bioconjugation via norbornene-tetrazine click chemistry. The utilities of these layered nanoparticles were demonstrated via enhanced protein sequestration, selective cell targeting (via PEGylation or altering polysaccharide coating), as well as loading and release of chemotherapeutic. The drug-loaded nanocarriers proved cytotoxic to J774A.1 monocytes and MOLM-14 leukemia cells.