International Journal of Nanomedicine (Sep 2019)
Targeted and pH-facilitated theranostic of orthotopic gastric cancer via phase-transformation doxorubicin-encapsulated nanoparticles enhanced by low-intensity focused ultrasound (LIFU) with reduced side effect
Abstract
Zhangluxi Liu,1 Haitao Ran,2 Zhigang Wang,2 Shiji Zhou,1 Yaxu Wang1 1Department of Gastrointestinal Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 2Institute of Ultrasound Imaging of Chongqing Medical University, Chongqing 400010, People’s Republic of ChinaCorrespondence: Yaxu Wang; Shiji ZhouDepartment of Gastrointestinal Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of ChinaEmail [email protected]; [email protected]: Focused ultrasound-mediated chemotherapy, as a non-invasive therapeutic modality, has been extensively explored in combating deep tumors for predominant penetration performance. However, the generally used high-intensity focused ultrasound (HIFU) inevitably jeopardizes normal tissue around the lesion for hyperthermal energy. To overcome this crucial issue, low-intensity focused ultrasound (LIFU) was introduced to fulfill precisely controlled imaging and therapy in lieu of HIFU. The objective of this study was to develop a facile and versatile nanoplatform (DPP-R) in response to LIFU and provide targeted drug delivery concurrently.Methods: Multifunctional DPP-R was fabricated by double emulsion method and carbodiimide method. Physicochemical properties of DPP-R were detected respectively and the bio-compatibility and bio-safety were evaluated by CCK-8 assay, blood analysis, and histologic section. The targeted ability, imaging function, and anti-tumor effect were demonstrated in vitro and vivo.Results: The synthetic DPP-R showed an average particle size at 367 nm, stable physical-chemical properties in different media, and high bio-compatibility and bio-safety. DPP-R was demonstrated to accumulate at the tumor site by active receptor/ligand reaction and passive EPR effect with intravenous administration. Stimulated by LIFU at the tumor site, phase-transformable PFH was vaporized in the core of the integration offering contrast-enhanced ultrasound imaging. The stimuli led to encapsulated DOX’s initial burst release and subsequent sustained release for anti-tumor therapy which was verified to be more effective and have less adverse effects than free DOX.Conclusion: DPP-R combined with LIFU provides a novel theranostic modality for GC treatment with potent therapeutic effect, including prominent performance of targeting, ultrasound imaging, and accurate drug release.Keywords: low-intensity focused ultrasound, nanoparticles, phase-transition, gastric cancer, targeted anti-cancer therapy
