Full Text | PDF

Theranostics 2019; 9(20):6002-6018. doi:10.7150/thno.36135 This issue Cite

Research Paper

Biodegradable, pH-Sensitive Hollow Mesoporous Organosilica Nanoparticle (HMON) with Controlled Release of Pirfenidone and Ultrasound-Target-Microbubble-Destruction (UTMD) for Pancreatic Cancer Treatment

Feng Gao^1#, Jianrong Wu^2#, Shiwei Niu^2#, Ting Sun¹, Fan Li¹, Yun Bai¹, Lifang Jin¹, Lizhou Lin¹, Qiusheng Shi^1✉, Li-Min Zhu^2✉, Lianfang Du^1✉

1. Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201600, P.R. China.
2. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P.R. China.
#: These authors contributed equally to this work.

✉ Corresponding authors: Lianfang Du, Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201600, P.R. China. Email: du_lfedu.cn; Li-Min Zhu, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P.R. China. Email: lzhuedu.cn; Qiusheng Shi, Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201600, P.R. China. Email: sqs19631989com More

Abstract

The dense extracellular matrix (ECM) and hypovascular networks were often found in solid pancreatic tumors form an impenetrable barrier, leading to limited uptake of chemotherapeutics and thus undesirable treatment outcomes.

Methods: A biodegradable nanoplatform based on hollow mesoporous organosilica nanoparticle (HMON) was designed as an effective delivery system for pirfenidone (PFD) to overcome the challenges in pancreatic tumor treatment. By varying pH producing a mildly acidic environment to emulate tumor cells, results in cleavage of the acetal bond between HMON nanoparticle and gating molecular, gemcitabine (Gem), enabling its controlled release.

Results: The in vitro and in vivo immunocytochemistry evaluations demonstrated an excellent ECM regulation efficacy of the nanoplatform and therefore the improved penetration of drug into the cells. The technique employed was especially enhanced when mediated with ultrasound target microbubble destruction (UTMD). Evaluations culminated with pancreatic cancer bearing mice and demonstrated therapeutic efficacy, good biodegradability, and negligible systemic toxicity.

Conclusion: the designed Gem gated biodegradable nanosystem is expected to provide an alternative way of improving antitumor efficacy by down-regulation of ECM levels and offers a passive-targeted therapy for pancreatic cancer treatment.

Keywords: Hollow mesoporous organosilica nanoparticles, biodegradability, ultrasound target microbubble destruction, extracellular matrix, gemcitabine gatekeeper

Citation styles

©2024 Ivyspring International Publisher. Terms of use