Gas‐Generating, pH‐Responsive Calcium Carbonate Hybrid Particles with Biomimetic Coating for Contrast‐Enhanced Ultrasound Imaging

Abstract

This work reports the fabrication of biocompatible and pH‐sensitive hybrid polydopamine/bovine serum albumin/calcium carbonate (PDA/BSA/CaCO3) particles via a rapid precipitation method. These hybrid particles generate hyperechogenic carbon dioxide bubbles upon exposure to low pH environments, making them ideal as a contrast agent and detector for tumor cells. This study also highlights the application of red blood cell membrane (RBC)‐derived membranes as a biomimetic coating for PDA/BSA/CaCO3 hybrid particles in order to modulate protein corona formation, a natural physiological response that alters tailored properties of most nanomaterials that are administered systemically. Results of this work demonstrate that the RBC membrane‐coated hybrid particles are ideal for a wide range of biomedical applications, such as noninvasive multimodal imaging, photothermal and photodynamic therapy, and “personalized” drug delivery systems.

Ultrasound-assisted fabrication of acoustically active, erythrocyte membrane “bubbles”

“…Among the materials being studied and applied in the last decade for biomedical applications, RBC or erythrocyte membranes are gaining significant research attention due to their inherent biocompatibility and their versatility in accommodating active payloads of different phases and sizes [10] , [11] , [12] . Since erythrocytes are naturally designed to stay in the bloodstream, the membranes derived from these cells can be used to cloak and protect the encapsulated payload, and prolong their circulation in the blood [13] , [14] , [15] , [16] . Despite the existing technologies that utilise RBC membranes as particle coating and emulsion stabiliser [10] , [11] , [12] , [17] , [18] , [19] , there have been no reports yet on the successful use of these cell membranes in fabricating ultrasound-responsive bubbles.…”

Smart Nanotheranostics Responsive to Pathological Stimuli

“…On the other hand, different materials can be manipulated in the nanoscale and dissolve (releasing a payload) in acidic pH. Calcium carbonate (CaCO 3 ) nanoparticles represent a wellinvestigated delivery platform (Idris et al, 2019;Vidallon et al, 2020) in this field. At physiological pH, CaCO 3 nanoparticles are stable, but under acid conditions, they degrade into Ca 2+ and CO 2 , releasing whatever payload was previously loaded.…”

Eco-friendly processes for the synthesis of amorphous calcium carbonate nanoparticles in ethanol and their stabilisation in aqueous media

“…In recent years, there has been increasing interest in calcium carbonate nanoparticles (CaCO 3 NPs) from various industrial fields. [1][2][3][4][5] Besides their excellent biocompatibility and biodegradability, they present numerous advantages for cosmetic formulations and biomedical applications. [6][7][8][9][10][11][12] For instance, they are intensively investigated for drug delivery, diagnostics and tumour therapy due to their pH responsive and buffering properties.…”

“…This includes the synthesis of CaCO 3 with stabilising molecules such as synthetic polymers, lipids or a combination of therapeutic molecules and synthetic polymers. 5,9,[32][33][34][35][36][37][38][39][40] The phase of the particles is generally not amorphous, with a mean diameter often higher than 300 nm. 5,9,32,33,35,36 Vidallon et al recently reported the synthesis of a hybrid polydopamine/bovine serum albumin/ CaCO 3 NPs stable in aqueous media for contrast-enhanced ultrasound imaging.…”