UNASSIGNED: RNA interference (RNAi) represents a powerful modality for @entity1 disease therapy that can regulate gene expression signature using small interfering RNA (siRNA). Successful delivery of siRNA into the cytoplasm of target cells is imperative for efficient RNAi and also constitutes the primary stumbling block in the clinical applicability of RNAi. Significant progress has been made in the development of lipid-based siRNA delivery systems, which have practical advantages like simple chemistry and easy formulation of nanoparticles with siRNA. This review discusses the recent development of @entity8487 , with particular focus on multifunctional @entity8487 for siRNA delivery. The key components of these multifunctional lipids include a protonatable @entity1472 head group, distal lipid tails, and two cross-linkable @entity1432 groups, which together facilitate the facile formation of stable siRNA-nanoparticles, easy surface modification for target-specific delivery, endosomal escape in response to the pH decrease during subcellular trafficking, and reductive dissociation of the siRNA-nanoparticles for cytoplasmic release of free siRNA. By virtue of these properties, multifunctional pH-sensitive lipids can mediate efficient cytosolic siRNA delivery and gene silencing. Targeted siRNA nanoparticles can be readily formulated with these lipids, without the need for other helper lipids, to promote systemic delivery of therapeutic siRNAs. Such targeted siRNA nanoparticles have been shown to effectively regulate the expression of @entity5 -related genes, resulting in significant efficacy in the treatment of aggressive @entity5 , including metastatic triple negative @entity0 . These multifunctional pH-sensitive lipids constitute a promising platform for the systemic and targeted delivery of therapeutic siRNA for the treatment of @entity1 diseases. This review summarizes the structure-property relationship of the multifunctional pH-sensitive lipids and their efficacy in in vitro and in vivo siRNA delivery and gene silencing.

Multifunctional pH-Sensitive XXXX Lipids for siRNA Delivery.

@entity1 :: ('9606', 'Species') :: ['human'] @entity1472 :: ('CHEBI:46882', 'Chemical') :: ['amino'] @entity8487 :: ('MESH:D010677', 'Disease') :: ['pH-sensitive amino lipids'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer', 'tumors'] @entity1432 :: ('CHEBI:29256', 'Chemical') :: ['thiol']
@entity1472 :: (CHEBI:46882,Chemical) :: ['Amino']
