Genetically Engineered Liposome‐like Nanovesicles as Active Targeted Transport Platform

Abstract

Ligand-targeted delivery of drug molecules to various types of tumor cells remains a major challenge in precision medicine. Inspired by the secretion process and natural cargo delivery functions of natural exosomes, biomimetic synthetic strategies are exploited to prepare biofunctionalized liposome-like nanovesicles (BLNs) that can artificially display a wide variety of targeting protein/peptide ligands and directly encapsulate medical agents for enhanced drug delivery. Here, as a proof of concept, genetically engineered BLNs, which display human epidermal growth factor (hEGF) or anti-HER2 Affibody as targeting moieties, are developed to, respectively, target two types of tumor cells. Notably, in comparison to synthetic liposomes covalently coupled with hEGF, it is demonstrated in this work that biosynthetically displayed hEGF ligands on BLNs possess higher biological activities and targeting capabilities. Additionally, treatments with doxorubicin-loaded BLNs displaying Affibody ligands exhibit much better antitumor therapeutic outcomes than clinically approved liposomal doxorubicin (Doxil) in HER2-overexpressing BT474 tumor xenograft models. These data suggest that BLN is suitable as a potent surrogate for conventional proteoliposomes or immunoliposomes as a result of excellent targeting capacities and facile production of BLNs.

Retracted: Ultrasound‐triggered breast tumor sonodynamic therapy through hematoporphyrin monomethyl ether‐loaded liposome

“…Liposomes are multilamellar or unilamellar phospholipidic submicroscopic vesicles allowing incorporation of hydrophilic and lipophilic drug due to their special properties (Rengan et al, 2015;Zhang et al, 2018). Biocompatible liposome can accumulate in tumor tissue via the enhanced permeability and retention (EPR) effect (Boyd, Galle, Daglas, Rosenfeld, & Medcalf, 2015;Kinoshita et al, 2015;Theek et al, 2016).…”

Bioinspired Artificial Nanodecoys for Hepatitis B Virus

“…[5] However, most MVs are surface engineered with functional motifs by chemical conjugation methods, which often suffer from poor biological stability and are limited in terms of in vivo delivery logistics and therapeutic activity. [6] It is clear that MVs engineered with highly stable “mimics” of receptor via a genetic modification procedure has the potential to address the limitations of receptor-mediated antiviral treatment with good specificity and safety profiles. [7] …”

“…[5] However,m ost MVs are surface engineered with functional motifs by chemical conjugation methods,w hich often suffer from poor biological stability and are limited in terms of in vivo delivery logistics and therapeutic activity. [6] It is clear that MVs engineered with highly stable "mimics" of receptor via agenetic modification procedure has the potential to address the limitations of receptor-mediated antiviral treatment with good specificity and safety profiles. [7] Human sodium taurocholate co-transporting polypeptide (hNTCP) is an ine-transmembrane transporter consisting of 349 amino acids with amolecular mass of 56 kD.hNTCP has been demonstrated as af unctional receptor of HBV and features essential high binding affinity for HBVpreS protein.…”

NanoTRAIL‐Oncology: A Strategic Approach in Cancer Research and Therapy

“…Therefore, novel carriers with long blood circulation and reduced RES uptake seem more appealing . Cell membrane‐derived nanovesicles (CMNs) are an emerging class of nanocarriers that are mainly formed by extracellular vehicles (EVs), cell plasma membranes, or TRAIL‐overexpressing normal cells . Due to their endogeneity, such naturally occurring nanocarriers are thought to be much safer and benign.…”