Hollow boron nitride nanospheres as boron reservoir for prostate cancer treatment

Xia Li,Nobutaka Hanagata,Xuebin Wang,Dmitri Golberg,Yoshio Bando,Atsuo Ito,Xiupeng Wang,Qunhong Weng,Jun Zhang

doi:10.1038/ncomms13936

Abstract

High global incidence of prostate cancer has led to a focus on prevention and treatment strategies to reduce the impact of this disease in public health. Boron compounds are increasingly recognized as preventative and chemotherapeutic agents. However, systemic administration of soluble boron compounds is hampered by their short half-life and low effectiveness. Here we report on hollow boron nitride (BN) spheres with controlled crystallinity and boron release that decrease cell viability and increase prostate cancer cell apoptosis. In vivo experiments on subcutaneous tumour mouse models treated with BN spheres demonstrated significant suppression of tumour growth. An orthotopic tumour growth model was also utilized and further confirmed the in vivo anti-cancer efficacy of BN spheres. Moreover, the administration of hollow BN spheres with paclitaxel leads to synergetic effects in the suppression of tumour growth. The work demonstrates that hollow BN spheres may function as a new agent for prostate cancer treatment.

Highlights

High global incidence of prostate cancer has led to a focus on prevention and treatment strategies to reduce the impact of this disease in public health
Boric acid (BA) decreases serum prostatespecific antigen (PSA) levels by 88%, inhibits the LNCap tumour growth by 38% and reduces insulin-like growth factor-1 in nude mice injected with human LNCap prostate cancer cells[15]
Hollow boron nitride (BN) spheres were synthesized via the chemical vapour deposition (CVD) reaction of trimethoxyborane (B(OMe)3) using modified method developed previously[39], in which the secondstage annealing process was conducted in Ar rather than in NH3 atmosphere

Summary

Introduction

High global incidence of prostate cancer has led to a focus on prevention and treatment strategies to reduce the impact of this disease in public health. Systemic administration of soluble B compounds, such as BA, associates with the drawbacks of its short half-life period, low bioavailability, requirement of frequent administration, low fraction arrived in the tumour site and limited effectiveness for prostate cancer treatments. The therapeutic window of BA for prostate cancer cells, which is B100 times higher than its average serum level in human, suggests difficulty in systemic administration of soluble B compounds without toxicity[14,21,23]. Local delivery of a sparsely soluble B-containing compound, as an alternative to soluble B compounds, might hold promise as a preventative and therapeutic agent for prostate cancer treatment. Male BALB/c-nu/nu mice were used to confirm the effects of hollow BN spheres on the suppression of prostate cancer occurrence and inhibition of tumour growth in vivo

Methods

Results

Conclusion