Theranostics 2018; 8(6):1665-1677. doi:10.7150/thno.22469

Research Paper

Porphyrin-grafted Lipid Microbubbles for the Enhanced Efficacy of Photodynamic Therapy in Prostate Cancer through Ultrasound-controlled In Situ Accumulation

Yujia You1,*, Xiaolong Liang2,*, Tinghui Yin1, Min Chen3, Chen Qiu1, Chuang Gao3, Xiaoyou Wang3, Yongjiang Mao1, Enze Qu1, Zhifei Dai3✉, Rongqin Zheng1✉

1. Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
2. Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China
3. Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
*These authors contributed equally to this work.

Abstract

Photodynamic therapy (PDT) holds promise for focal therapy of prostate cancer (PCa). However, the therapeutic efficacy needs improvement, and further development of PDT for PCa has challenges, including uncertainty of photosensitizers (PSs) accumulation at the tumor site and difficulty in visualizing lesions using conventional ultrasound (US) imaging. We have developed novel porphyrin-grafted lipid (PGL) microbubbles (MBs; PGL-MBs) and propose a strategy to integrate PGL-MBs with US imaging to address these limitations and enhance PDT efficacy.

Methods: PGL-MBs have two functions: imaging guidance by contrast-enhanced ultrasound (CEUS) and targeted delivery of PSs by ultrasound targeted microbubble destruction (UTMD). PGL-MBs were prepared and characterized before and after low-frequency US (LFUS) exposure. Then, in vitro studies validated the efficacy of PDT with PGL-MBs in human prostate cancer PC3 cells. PC3-xenografted nude mice were used to validate CEUS imaging, accumulation at the tumor site, and in vivo PDT efficacy.

Results: PGL-MBs showed good contrast enhancement for US imaging and were converted into nanoparticles upon LFUS exposure. The resulting uniquely structured nanoparticles avoided porphyrin fluorescence quenching and efficiently accumulated at the tumor site through the sonoporation effect created with the assistance of US to achieve excellent PDT efficacy.

Conclusions: This is the first preclinical investigation of MBs applied in PDT for PCa. PGL-MBs possess favorable CEUS imaging effects to enhance the localization of tumors. PGL-MBs with LFUS control PS accumulation at the tumor site to achieve highly effective PDT of PCa. This strategy carries enormous clinical potential for PCa management.

Keywords: porphyrin-grafted lipid, microbubbles, photosensitizer, ultrasound-targeted microbubble destruction, photodynamic therapy

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How to cite this article:
You Y, Liang X, Yin T, Chen M, Qiu C, Gao C, Wang X, Mao Y, Qu E, Dai Z, Zheng R. Porphyrin-grafted Lipid Microbubbles for the Enhanced Efficacy of Photodynamic Therapy in Prostate Cancer through Ultrasound-controlled In Situ Accumulation. Theranostics 2018; 8(6):1665-1677. doi:10.7150/thno.22469. Available from http://www.thno.org/v08p1665.htm