Yanling Lin, Harry Liu, Ines Garcia Carcedo, Li Li, Zhi Ping Xu, Michael Monteiro, Wenyi Gu*.

 

Building 75,Cnr College Rd & Cooper Rd
Australian Institute for Bioengineering and Nanotechnology
Brisbane City, QLD, Australia

 

Bisphosphonates (BPs) are a group of FDA approved drugs for bone diseases. They are the first-line therapy for osteoporosis and are also commonly used to treat bone or bone metastatic cancers. However, BPs are small molecules that have a short half-life in circulation, necessitating high dose and long-term use to be effective, which can cause severe side effects. Here we report to use our advanced nanotechnology to establish a bisphosphonate (BP) nanodrug platform using different BPs, which serves as both a novel nanodrug for treating bone diseases and a bone targeted drug delivery system. Using our nanotechnology we have synthesized different sizes of Calcium-BP Nanoparticles (Ca-BPNPs), which range from 50nm to 800nm. To evaluate the stability of our nanoparticles, we dissolved Ca-BPNPs in different pH buffers. We found that Ca-BPNPs are more stable in lower pH environment and dissolved after 48hours in pH 6 buffer while the similar Calcium Phosphate nanoparticles (CaPs) totally dissolved after 24 hours in pH 6 buffer1. Furthermore, we compared the efficiency of free BPs and Ca-BPNPs in different cells by MTT assay. We found that our Ca-BPNPs are more efficient than free BPs in killing both bone cancer cells (U2OS) and skin cancer cells (B16). More interestingly, our Ca-BPNPs shows higher affinity to Tumour Associated Macrophages (TAMs). Compared to murine RAW264.7 macrophage, Ca-BPNPs can kill approximately 20% more TAMs under the same drug concentration. As TAM plays an important role in tumour progression, targeting and killing TAM might limit the growth and migration of tumour cells. To verify our hypothesis, B16 cells and macrophage cells were co-cultured for a trans-well cell migration assays. The result of trans-well indicates that TAM can promote the migration of B16 cells. By adding Ca-BPNPs in the TAM cultured well, the amount of migrated B16 cells were remarkably decreased. Therefore, our particles can not only kill cancer cells but also inhibit the migration ability of tumour cells by killing TAM. This suggests that Ca-BPNPs may have wider potential applications in different kinds of cancer treatment. Meanwhile, we have explored the potential for the platform in targeted delivery, by harnessing the high affinity of BPs to bone using plasmid DNA and dsDNA-Cy5 as model drugs to U2OS cells with promising results. We believe that this BP nanodrug platform under developing will have wide application in managing bone diseases and related cancers.

References

[1] Dasgupta S, Bandyopadhyay A and Bose S., Acta Biomaterialia 2009, 5(8), 3112-3121. Reverse micelle-mediated synthesis of calcium phosphate nanocarriers for controlled release of bovine serum albumin

 

Biographic Details

Name: Yanling Lin

Affiliation, Country: AIBN, Australia

Phone: +61 4216688 E-mail: yanling.lin@uq.net.au