Lipid Nanoparticles as Enabling Platforms for mRNA Therapeutics: Biological Interfaces, Translational Progress, and Emerging Paradigms
Author:
Arvind Chansoria
Gajra Raja Medical College, Veer Savarkar Marg, Gwalior, Madhya Pradesh, India
Dilshad Ali Rizvi
Department of Pharmacology, Era's Lucknow Medical College and Hospital, Era
University, Lucknow, Uttar Pradesh, India
Salma Khan
Department of Pharmacology, Era's Lucknow Medical College and Hospital, Era
University, Lucknow, Uttar Pradesh, India
Abstract:
Background: Messenger RNA
(mRNA)-based therapies have fundamentally altered the landscape of modern drug
development by enabling controlled, short-lived production of therapeutic
proteins without permanent genomic modification. Despite clear mechanistic
advantages, clinical deployment was historically constrained by rapid enzymatic
degradation, inefficient cellular internalization, and activation of innate
immune responses.
Objective: This review critically
examines lipid nanoparticle (LNP) architecture, biological interactions,
intracellular trafficking, immunological modulation, manufacturing constraints,
and emerging technological innovations to provide a comprehensive understanding
of the current state and future trajectory of LNP-mediated mRNA delivery.
Methodology: A comprehensive narrative
review was conducted by systematically searching peer-reviewed literature from
PubMed, Scopus, and Web of Science databases (2001–2025), supplemented by
regulatory agency guidelines and authoritative clinical reports. Studies on LNP
formulation, mRNA delivery, vaccine platforms, oncology applications, protein
replacement, and genome editing were included.
Results:
LNPs
overcome the principal biological barriers to mRNA delivery through
multi-component lipid architectures incorporating ionizable lipids, helper
phospholipids, cholesterol, and PEG-conjugated lipids. The large-scale clinical
validation achieved through COVID-19 mRNA vaccines has accelerated expansion
into oncology, rare genetic disorders, protein supplementation, and in vivo
genome editing. Emerging platforms integrate phytomedicine-derived adjuvants
such as Withania somnifera and precision public health analytical frameworks to
further advance LNP-based therapeutic delivery.
Conclusion: LNPs represent a mature yet rapidly
evolving non-viral delivery platform. Continued advances in lipid chemistry,
immune modulation, organ-specific targeting, and precision public health
integration are expected to broaden the therapeutic spectrum of mRNA-based
interventions, establishing LNP-mediated delivery as a cornerstone of
next-generation precision medicine.
Keywords:
cancer vaccines, CRISPR delivery, gene therapy, Lipid nanoparticles, messenger RNA, mRNA therapeutics, non-viral delivery, nanomedicine, precision public health.