Modification of Lipid-Based Nanoparticles: An Efficient Delivery System for Nucleic Acid-Based Immunotherapy

Abstract

Lipid-based nanoparticles (LBNPs) are biocompatible and biodegradable vesicles that are considered to be one of the most efficient drug delivery platforms. Due to the prominent advantages, such as long circulation time, slow drug release, reduced toxicity, high transfection efficiency, and endosomal escape capacity, such synthetic nanoparticles have been widely used for carrying genetic therapeutics, particularly nucleic acids that can be applied in the treatment for various diseases, including congenital diseases, cancers, virus infections, and chronic inflammations. Despite great merits and multiple successful applications, many extracellular and intracellular barriers remain and greatly impair delivery efficacy and therapeutic outcomes. As such, the current state of knowledge and pitfalls regarding the gene delivery and construction of LBNPs will be initially summarized. In order to develop a new generation of LBNPs for improved delivery profiles and therapeutic effects, the modification strategies of LBNPs will be reviewed. On the basis of these developed modifications, the performance of LBNPs as therapeutic nanoplatforms have been greatly improved and extensively applied in immunotherapies, including infectious diseases and cancers. However, the therapeutic applications of LBNPs systems are still limited due to the undesirable endosomal escape, potential aggregation, and the inefficient encapsulation of therapeutics. Herein, we will review and discuss recent advances and remaining challenges in the development of LBNPs for nucleic acid-based immunotherapy.

Advances in Infectious Disease Vaccine Adjuvants

“…Lipid-based nanocarriers have been intensively used as vaccine adjuvants, with the ability to deliver nucleic acid antigens in vivo [ 243 ]. Lipid-based nanocarriers comprised of lipids and encapsulated nucleic acids (10–500 nm) have overcome system barriers, control the release time, and deliver antigens at the site of injection [ 243 , 244 ]. Formulations of lipid-based nanocarriers are affected by the lipid composition, the nucleic acid to lipid ratio, and formulation methods [ 243 ].…”

Using ncRNAs as Tools in Cancer Diagnosis and Treatment—The Way towards Personalized Medicine to Improve Patients’ Health

“…LNPs represent a well-established delivery system for gene therapies and are approved by the FDA for liver siRNA delivery [ 322 ]. LNPs offer several advantages, including enhanced drug stability, reduced toxicity, and control of the release rate [ 323 , 324 ]. Despite these promising aspects, several drawbacks remain to be addressed.…”

“…Despite these promising aspects, several drawbacks remain to be addressed. For example, small molecules are encapsulated with low efficiency; moreover, cytotoxicity and systemic toxicity problems remain to be solved [ 324 ]. The other RNA delivery systems include polymer-based nanoparticles.…”

Enhancing the Effect of Nucleic Acid Vaccines in the Treatment of HPV-Related Cancers: An Overview of Delivery Systems

“…However, because it was not directly employed as a delivery method for the DNA vaccine, it was not feasible to see a direct association with the reaction created by the vaccination. As for cationic nanoemulsions, they are colloidal particles consisting of an oily core in an aqueous phase stabilized by a cationic lipid or a combination of PEGylated lipids or phospholipids [155]. These nanoemulsions have the potential to inhibit particle aggregation, produce stability, and enhance endosomal escape [156].…”