Biomimetic Acoustically-Responsive Vesicles for Theranostic Applications

Abstract

In recent years, biomimetic cell membrane-derived particles have emerged as a new class of drug delivery system with advantages of biocompatibility, ease of isolation and long circulation profile. Here we report the development and potential theranostic applications of a new biomimetic acoustically-responsive droplet system derived from mammalian red blood cell membrane (RBCM). We hypothesized that drug-loaded RBCM droplets (RBCMDs) would undergo a transition from liquid (droplets) to gas (bubbles) upon high intensity focused ultrasound (HIFU) insonation, resulting in on-demand drug release. The generated microbubbles could also serve as a contrast agent to enhance ultrasound imaging. As-synthesized RBCMDs exhibited uniform size, good dispersity and preservation of RBCM-associated proteins that prevented uptake by macrophages. Camptothecin (CPT), an anti-cancer drug, was successfully loaded in the RBCMDs with a loading efficiency of 2-3% and an encapsulation efficiency of 62-97%. A short (3 min) exposure to HIFU irradiation triggered release of CPT from the RBCMDs and the physical explosion of droplets damaged nearby cancer cells resulting in significant cell death. In addition, the acoustically vaporized RBCMDs significantly increased the ultrasound echo signal to 30 dB. Lastly, we demonstrated that RBCMDs could be acoustically vaporized in vivo in target tissues, and enhancing ultrasound imaging. Taken together, we have developed a new class of naturally derived RBCMDs which show great potential for future application in remotely triggered drug delivery and ultrasound imaging enhancement.

Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application

“…In future, we may be able to overcome this limitation and extend this coating technology to other types and shapes of nanostructures. At the same time, various external stimuli such as near infrared-mediated photothermal effects, ultrasound 141 and magnetocaloric therapies have now been tried to enable the drug to be released on demand, which will be a new and broader area to study.…”

Cell membrane-derived nanomaterials for biomedical applications

“…The first such structures were derived from RBCs by extrusion of membrane ghosts and were termed nanoerythrosomes [138–141]. In addition to their cancer drug delivery roots, nanoerythrosomes can be used for the delivery of photoactivatable agents for imaging and photothermal therapy [142], antihypertensive drugs [143], and perfluorocarbons for acoustic responsiveness [144]. Nanoerythrosomes have also been bestowed additional targeting functionality via the conjugation of antibodies to a polymeric tether [145].…”

The Diverse Range of Possible Cell Membrane Interactions with Substrates: Drug Delivery, Interfaces and Mobility

“…Since the compositions of lipids and proteins vary by the source and determine cellular functions such as immunological impact, there have been attempts to coat biodegradable PLGA NPs with various types of cell membranes such as those of eukaryotic RBCs [ 39 ], cancer cells [ 42 ], platelets [ 43 ], leukocytes [ 50 ], and bacteria [ 40 , 51 ], as presented in Table 1 . Furthermore, a smart concept for hybrid-NPs was developed by adding a self-driving force since the incorporated NPs can be stimulated by various sources, such as magnetic fields [ 51 , 52 ], acoustic fields [ 53 , 54 , 55 ], electric fields [ 56 , 57 ], light [ 58 , 59 ], or chemical fuels [ 10 , 54 , 60 ] while upholding their bioavailability through their surface-anchored proteins. The control of the speed, directionality and temporal behavior of such nanomotors still needs to be investigated for the development of hybrid-NPs from native membranes.…”