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Abstract Microbubbles (MB) are widely used as contrast agents for ultrasound (US) imaging and US‐enhanced drug delivery. Polymeric MB are highly suitable for these applications because of their acoustic responsiveness, high drug loading capability, and ease of surface functionalization. While many studies have focused on using polymeric MB for diagnostic and therapeutic purposes, relatively little attention has thus far been paid to improving their inherent imaging and drug delivery features. This study here shows that manipulating the polymer chemistry of poly(butyl cyanoacrylate) (PBCA) MB via temporarily mixing the monomer with the monomer‐mimetic butyl cyanoacetate (BCC) during the polymerization process improves the drug loading capacity of PBCA MB by more than twofold, and the in vitro and in vivo acoustic responses of PBCA MB by more than tenfold. Computer simulations and physisorption experiments show that BCC manipulates the growth of PBCA polymer chains and creates nanocavities in the MB shell, endowing PBCA MB with greater drug entrapment capability and stronger acoustic properties. Notably, because BCC can be readily and completely removed during MB purification, the resulting formulation does not include any residual reagent beyond the ones already present in current PBCA‐based MB products, facilitating the potential translation of next‐generation PBCA MB.

Abstract Despite its high potential, non‐viral gene therapy of cancer remains challenging due to inefficient nucleic acid delivery. Ultrasound (US) with microbubbles (MB) can open biological barriers and thus improve DNA and mRNA passage. Polymeric MB are an interesting alternative to clinically used lipid‐coated MB because of their high stability, narrow size distribution, and easy functionalization. However, besides choosing the ideal MB, it remains unclear whether nanocarrier‐encapsulated mRNA should be administered separately (co‐administration) or conjugated to MB (co‐formulation). Therefore, the impact of poly(n‐butyl cyanoacrylate) MB co‐administration with mRNA‐DOTAP/DOPE lipoplexes or their co‐formulation on the transfection of cancer cells in vitro and in vivo is analyzed. Sonotransfection improved mRNA delivery into 4T1 breast cancer cells in vitro with co‐administration being more efficient than co‐formulation. In vivo, the co‐administration sonotransfection approach also resulted in higher transfection efficiency and reached deeper into the tumor tissue. On the contrary, co‐formulation mainly promoted transfection of endothelial and perivascular cells. Furthermore, the co‐formulation approach is much more dependent on the US trigger, resulting in significantly lower off‐site transfection. Thus, the findings indicate that the choice of co‐administration or co‐formulation in sonotransfection should depend on the targeted cell population, tolerable off‐site transfection, and the therapeutic purpose.

Abstract Tissue‐engineered vascular grafts (TEVGs) with the ability to grow and remodel open new perspectives for cardiovascular surgery. Equipping TEVGs with synthetic polymers and biological components provides a good compromise between high structural stability and biological adaptability. However, imaging approaches to control grafts’ structural integrity, physiological function, and remodeling during the entire transition between late in vitro maturation and early in vivo engraftment are mandatory for clinical implementation. Thus, a comprehensive molecular imaging concept using magnetic resonance imaging (MRI) and ultrasound (US) to monitor textile scaffold resorption, extracellular matrix (ECM) remodeling, and endothelial integrity in TEVGs is presented here. Superparamagnetic iron‐oxide nanoparticles (SPION) incorporated in biodegradable poly(lactic‐co‐glycolic acid) (PLGA) fibers of the TEVGs allow to quantitatively monitor scaffold resorption via MRI both in vitro and in vivo. Additionally, ECM formation can be depicted by molecular MRI using elastin‐ and collagen‐targeted probes. Finally, molecular US of αvβ3 integrins confirms the absence of endothelial dysfunction; the latter is provocable by TNF‐α. In conclusion, the successful employment of noninvasive molecular imaging to longitudinally evaluate TEVGs remodeling is demonstrated. This approach may foster its translation from in vitro quality control assessment to in vivo applications to ensure proper prostheses engraftment.