Biodegradable nanotheranostics with hyperthermia-induced bubble ability for ultrasound imaging–guided chemo-photothermal therapy

Abstract

Changsong Xu1,2,*, Feng Gao3,*, Jianrong Wu4, Shiwei Niu4, Fan Li3, Lifang Jin3, Qiusheng Shi3, Lianfang Du1,3 1Department of Ultrasound, Shanghai General Hospital of Nanjing Medical University, Shanghai 201600, People’s Republic of China; 2Department of Ultrasound, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an City, Jiangsu 223300, People’s Republic of China; 3Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201600, People’s Republic of China; 4College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiusheng ShiShanghai General Hospital, Shanghai Jiaotong University School of Medicine, 650 Xin Songjiang Road, Songjiang District, Shanghai 201600, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] DuDepartment of Ultrasound, Shanghai General Hospital of Nanjing Medical University, 650 Xin Songjiang Road, Songjiang District, Shanghai 201600, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Theranostics, elaborately integrating both therapeutic and diagnostic functions into a nanoplatform holds great potential for precision cancer medicine.Methods: Herein, a biodegradable theranostic nanoplatform with hyperthermia-induced bubble ability for highly efficient ultrasound (US) imaging–guided chemo-photothermal therapy of breast tumors was developed. The prepared nanoparticles consisted of polydopamine (PDA)-modified hollow mesoporous organosilica nanoparticles (HMONs) with approximately 75 nm in diameter for doxorubicin (DOX) loading and perfluoropentane (PFP) filling. In addition, the pH-sensitive PDA coating served as both gatekeeper controlling DOX release and photothermal agent for inducing hyperthermia.Results: Such nanoplatform (PDA@HMONs-DOX/PFP, PHDP) provides efficient loading (328 mg/g) and controllable stimuli-responsive release of DOX for chemotherapy. The incorporated disulfide bonds in the framework of HMONs endowed nanoparticles with intrinsic glutathione-responsive biodegradability and improved biocompatibility. Benefiting from the hyperthermia upon an 808-nm laser irradiation of PDA, the liquid–gas phase transition of the loaded PFP was induced, resulting in the generation of the nanobubbles, followed by the coalescence into microbubbles. This conversation could enhance the tumor cell uptake of nanoparticles, as well as intensify the US imaging signals. In addition, a synergistic therapeutic effect of our fabricated nanoplatform on cells/tumor growth effect has been systematically evaluated both in vitro and in vivo.Conclusion: Therefore, such “all-in-one” PHDP nanoparticles with satisfactory biocompatibility and biodegradability, hyperthermia-induced bubble ability and simultaneous US imaging performance hold great potential for cancer nanotheranostics.Keywords: biodegradable, bubble, hollow mesoporous organosilica, nanotheranostics, synergistic therapy

Keywords

• Biodegradable
• bubble
• hollow mesoporous organosilica
• nanotheranostics
• synergistic therapy