Systematic design of DMBT1-derived peptides correlating physicochemical properties and sequence motifs with siRNA delivery and efficacy in cancer therapy.

ABSTRACT:

Background

Molecules driving the cancer process are frequently difficult to target with traditional small-molecule drugs. Small interfering RNAs (siRNAs) offer high specificity, but their clinical translation is hindered by inefficient delivery and rapid degradation. We previously identified DMBT1-derived cell-penetrating peptides (CPPs) that encapsulate siRNA and improve serum stability in vitro.

Methods

We designed 37 DMBT1-derived peptides using a rational, high-throughput pipeline to enhance siRNA encapsulation, stability, and delivery. Binding, uptake, and silencing were assessed in A375 and MCF7 cells. Regression and motif discovery analyses were applied to link peptide physicochemical features with encapsulation efficiency, serum stability, and gene silencing.

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SUBMITTER: Tuttolomondo M 

PROVIDER: S-EPMC12590273 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature