ArticleDrug delivery and translational research2026
Double-coated PLGA nanoparticles with hierarchical surface architecture for CD44-targeted siRNA delivery.
Article in Drug delivery and translational research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors.
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Abstract
Efficient delivery of small interfering RNA (siRNA) remains a materials challenge because it requires nanocarriers that stabilize polyanionic cargo, support cellular interactions, and enable cytosolic delivery. Although poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are used due to biocompatibility, biodegradability, and regulatory acceptance, siRNA delivery with PLGA requires interfacial engineering to meet these constraints. Here, a modular double-coated PLGA NP platform (dcNPs2.0) is developed and optimized for siRNA complexation, surface functionalization, and scalable manufacturing. The system comprises a PLGA core coated with a polyethyleneimine (PEI) interlayer to mediate siRNA binding, followed by a hyaluronic acid (HA) outer layer, which improves colloidal stability and promotes CD44-mediated uptake. Process optimization, including transition from batch nanoprecipitation to microfluidic fabrication, provides high yield, excellent reproducibility, narrow size distributions, and increased siRNA loading. X-ray photoelectron spectroscopy confirms hierarchical multilayer assembly. The optimized dcNPs2.0 formulation exhibited robust physicochemical stability during storage, in serum-containing media, and following lyophilization with appropriate cryoprotection. Functional evaluation of dcNPs2.0 demonstrated efficient HA-mediated cellular uptake and effective silencing following siRNA delivery in both two-dimensional monolayers and three-dimensional spheroids of MDA-MB-231 cells. Overall, this work establishes a scalable, rationally engineered PLGA nanoplatform that integrates extracellular targeting with intracellular delivery requirements for siRNA therapeutic applications.
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