Alendronate-conjugated liposome for targeting of osteoblastic prostate cancer: evaluation of binding to bone matrix and in vivo targeting in a mouse model.

Prostate cancer bone metastases are predominantly osteoblastic, placing them in a unique position for bone-targeted drug delivery. Bone-targeted nanoparticles may be able to accumulate in aberrant bone formation inside these osteoblastic tumours, but this has not been explored. Here, we developed an alendronate-conjugated liposome (Lip-Cy5.5-Aln) encapsulating the near-infra-red dye Cy5.5 as a model payload to evaluate targeting. Binding to bone matrix was assessed in vitro using hydroxyapatite, MC3T3-E1-derived osteoblasts and 2H11-derived osteoblast-like cells. In vivo targeting of bone and bone-forming tumours was assessed in male nude mice with or without subcutaneous C4-2B (non-osteoblastic) or C4-2B-BMP4 (osteoblastic) tumours using optical imaging and non-targeted liposomes as control. Lip-Cy5.5-Aln selectively bound to bone matrix in vitro as opposed to control (57.4% vs. 0.6%, p < 0.0001). In vivo, Lip-Cy5.5-Aln exhibited increased musculoskeletal accumulation (51.0% vs. 39.8%, p < 0.0001) and reduced kidney localisation (18.4% vs. 29.9%, p < 0.0001). However, there was no significant difference in Cy5.5 signal between Lip-Cy5.5-Aln and control in bone-forming C4-2B-BMP4 tumours, nor was localisation greater in osteoblastic versus non-osteoblastic tumours. Overall, the alendronate-conjugated liposome showed enhanced musculoskeletal accumulation, but it does not seem to effectively target pathologic intratumour bone formation in metastatic prostate cancer.