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

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 Gao1#, Jianrong Wu2#, Shiwei Niu2#, Ting Sun1, Fan Li1, Yun Bai1, Lifang Jin1, Lizhou Lin1, Qiusheng Shi1✉, Li-Min Zhu2✉, Lianfang Du1✉

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.

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Citation:
Gao F, Wu J, Niu S, Sun T, Li F, Bai Y, Jin L, Lin L, Shi Q, Zhu LM, Du L. Biodegradable, pH-Sensitive Hollow Mesoporous Organosilica Nanoparticle (HMON) with Controlled Release of Pirfenidone and Ultrasound-Target-Microbubble-Destruction (UTMD) for Pancreatic Cancer Treatment. Theranostics 2019; 9(20):6002-6018. doi:10.7150/thno.36135. Available from https://www.thno.org/v09p6002.htm

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Abstract

Graphic 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