Silica nanoparticles as advanced platforms for nucleic acid delivery

TL;DR

Silica nanoparticles offer a promising solution for delivering nucleic acids by providing stability, protection, and controlled release, addressing key challenges in gene therapy.

Contribution

The paper introduces silica-based nanoparticles as advanced, structurally durable, and chemically adaptable platforms for efficient nucleic acid delivery.

Findings

Silica nanoparticles provide mechanical rigidity and tunable porosity for robust nucleic acid encapsulation.

Hybrid and biomimetic silica platforms enable combinatorial and theranostic functionalities for complex payloads.

Silica nanocarriers can overcome systemic and intracellular barriers like degradation, immune recognition, and endosomal escape.

Abstract

Nucleic acid therapeutics, including siRNA, mRNA, plasmid DNA, and CRISPR/Cas systems, have demonstrated remarkable potential but continue to face translational barriers related to systemic instability, immune activation, and inefficient intracellular delivery. Conventional lipid and polymeric carriers, although clinically validated, often lack the structural resilience and versatility required for large or complex cargos. Silica-based nanoparticles, particularly mesoporous silica nanoparticles, provide a distinctive combination of mechanical rigidity, tunable porosity, and abundant surface chemistry that enables robust encapsulation, protection, and controlled release of diverse nucleic acids.

This review adopts a problem-driven perspective, analyzing how specific nanoarchitectural designs, surface functionalizations, and ligand-mediated targeting strategies address key limitations in nucleic acid delivery. Emphasis is placed on overcoming systemic barriers such as premature degradation, immune recognition, and restricted biodistribution, as well as intracellular challenges including endosomal escape and nuclear access. Hybrid and biomimetic silica platforms are highlighted for their capacity to integrate combinatorial and theranostic functionalities, expanding the therapeutic scope toward complex payloads and multifunctional formulations.

By linking synthesis approaches with translational requirements, an integrated roadmap is proposed that positions silica nanocarriers as advanced platforms for next-generation gene therapy. The evidence underscores the potential of silica architectures to combine structural durability with versatile chemical adaptability, thereby enabling safe, efficient, and clinically relevant delivery of nucleic acids.

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