Drug-Loaded Acoustic Nanodroplet for Dual-Imaging Guided Highly Efficient Chemotherapy Against Nasopharyngeal Carcinoma

Abstract

Dayan Yang,* Qiqing Chen,* Min Zhang, Guiying Feng, Dandan Sun, Ling Lin, Xiangxiang Jing Department of Ultrasonography, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Hainan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Lin, Tel [phone], Email [email protected] Xiangxiang Jing, Email [email protected]: Chemotherapy is an important approach to treating nasopharyngeal carcinoma (NPC). Unfortunately, the lack of selectivity, insufficient tumor accumulation, uneven tumor distribution and severe systemic toxicity lead to the unsatisfactory performance of these drugs. While a more precise drug delivery, on-demand drug release, and deep diffusion of drugs (homogeneous distribution of drugs in the tumor) could improve the application, they remain challenging. Chemotherapeutic drug-loaded acoustic nanodroplet with dual-imaging capacity is expected to solve these problems.Methods: Folate (Fa)-modified and doxorubicin (Dox)-loaded acoustic poly (lactic‐co‐glycolic acid) (PLGA), low intensity focused ultrasound (LIFU)-responsive perfluoropentane (PFP) and Fe3O4 nanoparticles (designated as Fa-Fe@P-PFP-Dox) were integrated by a double-emulsion method. After the synthesis, the LIFU-triggered acoustic droplet vaporization (ADV) effect, LIFU-triggered drug release, cell targeting capability, in vitro cell-killing effects, biodistribution, PA/MR dual imaging (PA: photoacoustic; MR: magnetic resonance), LIFU-augmented Dox distribution in tumors and chemotherapeutic efficacy of Fa-Fe@P-PFP-Dox were investigated.Results: The distribution of these drug-loaded nanodroplets was clearly monitored via PA/MR dual imaging. Upon LIFU irradiation, PFP within the Fa-Fe@P-PFP-Dox nanodroplets underwent ADV, which led to the release of Dox and promoted the deep penetration of Dox in tumor tissue, eventually achieving highly efficient chemotherapy against NPC. As a result, LIFU-triggered chemotherapy exerted a highly efficient therapeutic effect with a tumor inhibition rate of 74.24 ± 7.95%.Conclusion: Fa-modified and drug-loaded acoustic nanodroplets have been successfully constructed for dual-imaging guided highly efficient chemotherapy against NPC. This novel tumor drug delivery method is expected to provide an efficient, visualized, and precise personalized treatment method for NPC patients with minimal side effects.Keywords: nasopharyngeal carcinoma, drug delivery, low intensity focused ultrasound, chemotherapy, deep penetration

Keywords

• nasopharyngeal carcinoma
• drug delivery
• low intensity focused ultrasound
• chemotherapy
• deep penetration