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Updated: Oct 15, 2026

Preparation, Purification, and Use of Fatty Acid-containing Liposomes
Published on: February 9, 2018
Chemically tailored lipids mediate solid-phase RNA programming of mineralized microenvironments
Jingyi Liu1, Qinyuan Chen2, Jedtanut Thussananutiyakul3
1Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, United States; Department of Preventive & Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States.
Abstract:
The localized delivery of RNA therapeutics to mineralized tissue interfaces is limited by poor retention and rapid clearance at the target site. We report the development of a solid-phase transfection platform that functionalizes mineralized surfaces into bioactive nucleic acid reservoirs. Through the rational design and screening of a library of 21 piperazine-linked bisphosphonate ionizable lipids, we identified a lead formulation of bisphosphonate lipid nanoparticle (BP-LNP) that maximizes hydroxyapatite affinity without compromising transfection potency. Upon adsorption onto mineral substrates, these BP-LNPs resisted fluid removal and maintained surface-mediated, sustained delivery of encapsulated RNA cargo to adjacent cells. We demonstrated the versatility of this Mineralized Tissue-Targeting Expression System (MiTEX) composed of BP-LNPs in two therapeutic contexts: Cre recombinase mRNA-functionalized allogeneic bone grafts to genetically label de novo bone formation in vivo, and STAT3 siRNA delivery to reduce inflammation in human gingival explants. This platform provides a universal strategy for transforming inert calcium phosphate materials and tissues into locally bioactive RNA delivery systems for regenerative and immunomodulatory applications.
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