<p>Lipid nanobubbles as an ultrasound-triggered artesunate delivery system for imaging-guided, tumor-targeted chemotherapy</p>

Abstract

Purpose Herein, this study is to prepare folic acid (FA)-conjugated lipid nanobubbles (NBs) that highly load artesunate (Arte; FA-ALNBs), as an ultrasound (US)-triggered Arte delivery system for imaging-guided, tumor-targeted chemotherapy. Materials and methods The morphology, size, zeta potential, and stability of the FA-ALNBs were detected by optical microscopy and dynamic light scattering analysis. The cellular uptake of the FA-ALNBs was evaluated by confocal laser scanning microscopy and flow cytometry. Results The FA-ALNBs showed uniform spheroidal structure, with 781.2±5.3 nm in average diameter, great physiological stability, and ~91.9%±1.1% encapsulation efficiency of Arte. Using focused US, about 36.1%±2.5% of the entrapped Arte was trigger-released from the FA-ALNBs. Owing to the US contrast property, FA-ALNBs showed an enhanced US signal in vitro when using an ultrasonic diagnostic apparatus with a 1-MHz linear transducer. Due to the FA receptor-mediated endocytosis effect, FA-ALNBs can be efficiently internalized by cells, showing an uptake ratio of about 56.4%±3.1%. FA-ALNBs showed an enhanced, dose-dependent cell-killing ability, while FA-ALNBs plus US irradiation exhibited a stronger anticancer effect in vitro. Post intravenous injection into tumor-bearing mice, FA-ALNBs showed an enhanced US contrast effect with increase in time, indicating the increasing accumulation of FA-ALNBs in tumor tissue, which peaked at 4 hours post injection. Focused US irradiation was conducted on the tumor region at 4 hours post injection of FA-ALNBs, which showed a greater tumor suppression effect after 30 days of treatment compared with all other treatment groups. Moreover, FA-ALNBs showed negligible systemic toxicity in vivo. Conclusion This versatile US-triggered drug delivery system with great anticancer efficacy was assessed both in vitro and in vivo, revealing great potential as a cancer theranostic agent for future application.

<p>Albumin exfoliated titanium disulfide nanosheet: a multifunctional nanoplatform for synergistic photothermal/radiation colon cancer therapy</p>

“…The accumulation of TiS 2 -HSA-FA in tumor was likely due to the FA modification, which is known to facilitate tumor targeting. 44,45 As shown in Figure 5C, after intravenous injection, blood distribution half-life (t 1/2 α) and blood terminal elimination half-life (t 1/2 β) of the TiS 2 -HSA-FA were 1.21±0.11 hrs and 17.52±0.62 hrs, respectively. It has been reported that PEG and HSA modifications can prolong blood circulation and reduce macrophage clearance of nanoparticles from the reticuloendothelial system.…”

Current advances in ultrasound-combined nanobubbles for cancer-targeted therapy: a review of the current status and future perspectives

“…Also, the FA-ALNBs did not exhibit any signicant toxic effect. 90 PFB-NBs were co-loaded onto liposomes of less than 300 nm in diameter with a model compound. The subsequent nested-NBs demonstrated strong ultrasonic echo at conspicuous ultrasonic imaging frequencies between 3 MHz and 8 MHz.…”

“…Some other recent studies have also shown that NBs have no systemic toxicity in vivo, which is ideal for their future clinical application in anticancer therapy. 113,114 Although the comprehensive safety assessment remains inadequate, this will be the subject of future research. 115 Furthermore, if the use of the nanobubbles is benecial for treatment, then the effort to translate them into clinical applications will be worth it.…”

pH- and acoustic-responsive platforms based on perfluoropentane-loaded protein nanoparticles for ovarian tumor-targeted ultrasound imaging and therapy

“…Ultrasound (US) technology, due to its non-invasive, non-radiative, low-cost, and specific characteristics, is widely used in clinical diagnosis and tumor treatments [10][11][12]. In recent decades, an acoustic response platform (ARP) with US imaging and therapeutic capabilities has been developed for effective tumor diagnosis and treatment [13][14][15][16]. ARP mainly includes microbubbles or nanobubbles (MB or NB) and nanoparticle (NP) based platforms [16,17].…”