RESUMO
INTRODUCTION: Adequate transfection efficiency is indispensable to safe and effective delivery of therapeutically active agents, particularly in cancer. Endosomal escape is regarded as a critical and determining step devoted a significant number of studies of the drug/gene delivery field. AREAS COVERED: This paper critically reviews the fundamental properties of chloroquine (CQ), its pharmacokinetics, pharmacodynamics, and clinical applications and the present knowledge of CQ application as an endosomal escape enhancing agent. Different approaches to enhance the endosomal escape process of nanoparticles have been introduced including use of endosomal escape enhancing agents. Application of CQ as either a pre-treatment modality in which cells or animals are exposed to CQ prior to the main treatment or a component of co-delivery systems where CQ and other anti-cancer agents are simultaneously entered the cancer cells, is discussed with recent studies. EXPERT OPINION: CQ is founded to intervene with the natural process of endosomal maturation. Moreover, CQ seems to increase the effectiveness of gene delivery by its electrostatic interaction with negatively charged components of the transferred genetic molecules. Endosomal escape might be regarded as the bottleneck of efficient gene delivery and CQ as an effective and available endosomal escape enhancing agent deserves more sophisticated studies.
Assuntos
Nanopartículas , Preparações Farmacêuticas , Animais , Cloroquina/farmacologia , Endossomos , Humanos , TransfecçãoRESUMO
Many biological mechanisms including cellular metabolism and cell death are regulated by mitochondria known as powerhouse of the cell. Recently, let-7b, a tumour-suppressor microRNA has been detected in mitochondria of human cells targeting several mitochondrial-encoded respiratory chain genes. Triphenylphosphonium cation (TPP) is one of the major classes of mitochondriotropics that possess the ability of specifically targeting the mitochondria. PAMAM dendrimers are one of the most available agents in gene delivery due to their well-defined and beneficial features such as large density of surface functional groups. Hyaluronic acid (HA), a natural polysaccharide has been demonstrated to have the abilities such as good biocompatibility and targeting CD44 overexpressed receptors on non-small cell lung cancer (NSCLC) cells. In this research, let-7b-PAMAM (G5)-TPP and let-7b-PAMAM (G5)-TPP-HA nano-carriers were designed to deliver let-7b miRNA mimic to NSCLC cells' mitochondria as a novel way of cancer cells inhibition. Nano-carriers were capable of being successfully taken up by A549 cells and localised in mitochondria environment. Let-7b loaded nanoparticles reduced cell viability and induced apoptosis significantly. Expression of genes involved in mitochondrial oxidative function was decreased resulting in nanoparticles effect on mitochondria. Application of mitochondria targeted-miRNA delivery systems could regulate cellular functions to inhibit lung cancer.