Enhanced Stable Cavitation and Nonlinear Acoustic Properties of Poly(butyl cyanoacrylate) Polymeric Microbubbles after Bioconjugation

Abstract

Microbubbles (MB) are used as ultrasound (US) contrast agents in clinical settings because of their ability to oscillate upon exposure to acoustic pulses and generate nonlinear responses with a stable cavitation profile. Polymeric MB have recently attracted increasing attention as molecular imaging probes and drug delivery agents based on their tailorable acoustic responses, high drug loading capacity, and surface functionalization capabilities. While many of these applications require MB to be functionalized with biological ligands, the impact of bioconjugation on polymeric MB cavitation and acoustic properties remains poorly understood. Hence, we here evaluated the effects of MB shell hydrolysis and subsequent streptavidin conjugation on the acoustic behavior of poly(butyl cyanoacrylate) (PBCA) MB. We show that upon biofunctionalization, MB display higher acoustic stability, stronger stable cavitation, and enhanced second harmonic generation. Furthermore, functionalized MB preserve the binding capabilities of streptavidin conjugated on their surface. These findings provide insights into the effects of bioconjugation chemistry on polymeric MB acoustic properties, and they contribute to improving the performance of polymer-based US imaging and theranostic agents.

Hybrid ultrasound and photoacoustic contrast agent designs combining metal phthalocyanines and PBCA microbubbles

“…The MB mean diameter was around 2.3 μm, which was consistent with our previous studies. 25,35 The narrow diameter distributions of the MB samples were additionally confirmed by wide-area OM (Fig. S2, ESI†).…”

“…This is important, since variations in MB size and shell characteristics may alter (or even hamper) the MB acoustic properties. 35,48…”

“…This is important, since variations in MB size and shell characteristics may alter (or even hamper) the MB acoustic properties. 35,48 The efficiency of dye encapsulation dictates the PA contrast capabilities of the resulting platform, as higher levels of chromophores encapsulated in the MB shell are likely to provide stronger optical properties. Fig.…”

“…PBCA MB were synthesized via anionic polymerization of BCA monomers in the presence of hydroxyl ions as previously described. 25,35,36 Briefly, an aqueous solution of 1% (v/v) Triton X-100 was prepared, and the pH of the solution was adjusted to 2.5. Next, 1% (v/v) of BCA were added dropwise to the solution at room temperature, and the resulting mixture was stirred for 1 h at 10 000 rpm using an Ultra-Turrax T50 (IKA-Werke, Staufen, Germany).…”

Polymeric materials for ultrasound imaging and therapy

“…For example, partial shell hydrolysis and subsequent streptavidin shell functionalization improved the stable cavitation prole and enhanced second harmonic generation of PBCA MB, since the process decreased the rigidity of the MB shell. 79 4. Emerging applications of polymeric microbubbles…”