One‐Step Formation of Targeted Liposomes in a Versatile Microfluidic Mixing Device

Abstract

Targeted liposomes, as a promising carrier, have received tremendous attention in COVID‐19 vaccines, molecular imaging, and cancer treatment, due to their enhanced cellular uptake and payload accumulation at target sites. However, the conventional methods for preparing targeted liposomes still suffer from limitations, including complex operation, time‐consuming, and poor reproducibility. Herein, a facile and scalable strategy is developed for one‐step construction of targeted liposomes using a versatile microfluidic mixing device (MMD). The engineered MMD provides an advanced synthesis platform for multifunctional liposome with high production rate and controllability. To validate the method, a programmed death‐ligand 1 (PD‐L1)‐targeting aptamer modified indocyanine green (ICG)‐liposome (Apt‐ICG@Lip) is successfully constructed via the MMD. ICG and the PD‐L1‐targeting aptamer are used as model drug and targeting moiety, respectively. The Apt‐ICG@Lip has high encapsulation efficiency (89.9 ± 1.4%) and small mean diameter (129.16 ± 5.48 nm). In vivo studies (PD‐L1‐expressing tumor models) show that Apt‐ICG@Lip can realize PD‐L1 targeted photoacoustic imaging, fluorescence imaging, and photothermal therapy. To verify the versatility of this approach, various targeted liposomes with different functions are further prepared and investigated. These experimental results demonstrate that this method is concise, efficient, and scalable to prepare multifunctional targeted liposomal nanoplatforms for molecular imaging and disease theranostics.

Recent advances in nanotechnology for programmed death ligand 1-targeted cancer theranostics

“…For instance, Shan et al developed a versatile microfluidic mixing device to construct Apt-ICG@Lip as NIR-II nanoprobes. 52 Apt-ICG@Lip was intravenously injected into Lewis Lung Cancer (LLC) tumor-bearing mice to evaluate the PD-L1 expression level. LNPs improved the solubility, circulation lifetime, and sustained the FL intensity of ICG, which persisted at the tumor site for 24 h (Fig.…”

“…Fig.6(a) Fluorescence images of mice at different time points post intravenous injection of Apt-ICG@Lip and ICG@Lip 52. Copyright 2023, Wiley-VCH GmbH.…”

Recent Advances in Microfluidic Technologies for the Construction of Artificial Cells

“…Zhao and co‐workers developed a versatile microfluidic mixing device (MMD) for a controllable and rapid production of homogeneous aptamer‐functionalized liposomes. [ 81 ] A programmed death‐ligand 1 (PD‐L1)‐targeting aptamer‐modified indocyanine green (ICG)‐liposome (Apt‐ICG@Lip) was produced through the MMD, which can be potentially used for targeted photoacoustic imaging, fluorescence imaging, and photothermal therapy.…”

“…Lipid‐based vesicles, also known as liposomes, are generally formed by curved phospholipid bilayers. [ 81 ] They have been extensively used as a promising model of artificial cells due to their excellent biocompatibility and versatility. Up to now, liposomes have been widely employed in drug delivery systems and to mimic complex biological phenomena that occur inside natural cells.…”

Vortex fluidic regulated phospholipid equilibria involving liposomes down to sub-micelle size assemblies

“…5,11 These challenges include complex time consuming operations, limited reproducibility, and scaling up. They arise from restrictions associated with the prevailing focus of the micro-uidic hydrodynamic approach (MHF), as a lab-on-a-chip device, 5 with recent advances in overcoming them using a microuidic mixing device, 11 with future prospects on using machine learning in the microuidic processing. 12 An alternative approach is using the recently developed thin lm micro-uidic platform, the vortex uidic device (VFD), Fig.…”