Non-Modified Ultrasound-Responsive Gas Vesicles from Microcystis with Targeted Tumor Accumulation

INTRODUCTION: Ultrasonic molecular imaging (UMI) technology has attracted increasing interest because of its low cost and capability to evaluate changes rapidly and noninvasively at the cellular and molecular levels. The key material of this technology is ultrasound-responsive gas vesicles (GVs). GVs synthesized by conventional chemical methods have several limitations, such as high costs, low yields, and complex production processes. In comparison, biosynthesized GVs have the advantages of high stability, a low risk of toxicity, genetic engineering characterization, easy post modification and drug loading potential. However, translational studies of their biosynthesis are still in their infancy; in particular, the duration of GVs in the circulatory system is essential for the usage of UMI in biomedicine and the clinic. RESULTS: Here, we report novel GVs biosynthesized by the cyanobacterium Microcystis, which have a moderate size, a negative zeta potential, a rod-like morphology, and a protein-shelled gas-contained structure. These GVs without any chemical modifications could be detected in the mice circulatory system for more than 10 hours by clinically used ultrasound scanners. In particular, GVs can accumulate in tumors via the enhanced permeation and retention (EPR) effect 11 hours post-injection, and lasting at least 2 hours, which might be a potential aid for tumor diagnosis. Furthermore, pathological and hematological study suggested that GVs are safe for the host. CONCLUSION: We concluded that the GVs synthesized by Microcystis without any modifications have UMI potential for systemic evaluation as well as tumoral diagnosis after intravenous injection.