Submission Date

7-23-2026

Document Type

Paper- Restricted to Campus Access

Department

Chemistry

Faculty Mentor

Samantha Wilner

Comments

Presented during the 28th Annual Summer Fellows Symposium, July 24, 2026 at Ursinus College.

Project Description

Nucleic acids, such as RNA and DNA, have been used to treat a variety of diseases by having therapeutic effects, such as gene silencing or immune stimulation. However, nucleic acids have a hard time getting into the cells due to their size and negative charge. Lipid nanoparticles (LNPs), which encapsulate nucleic acids, are the leading drug delivery method for these therapeutics; however, LNPs consist of four components, making the system complex. Here, we investigate an alternative strategy for the delivery of nucleic acid therapeutics using ionizable amphiphilic Janus dendrimers (IAJDs), specifically IAJD 97, which produces one-component dendrimersome nanoparticles (DNPs). IAJD 97 is inexpensive to synthesize and commercially available, potentially providing a better alternative to LNPs. To develop this approach, DNPs encapsulating poly-adenylated (poly-A) mRNA were assembled from IAJD 97, using ethanol injection or microfluidic mixing. Variables such as salt concentration and buffer pH were also changed, and dynamic light scattering (DLS) was used to measure the size and homogeneity of the nanoparticles. Results indicate that salt lowers the homogeneity, or polydispersity index, of DNPs prepared by ethanol injection. Future research will investigate how these biophysical changes affect mRNA encapsulation and interactions of DNPs with biological proteins. From this research, we can determine how the structure of DNPs affects drug delivery, which can eventually lead to therapeutic treatments of diseases.

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