Bone-targeted PAMAM micelle to treat bone metastases of lung cancer

Background: Bone is a frequent site of metastasis in lung cancer patients. So far, the treatment in bone metastasis of lung cancer still has not achieved any satisfactory effects in clinic. In this paper, alendronate (ALN) was selected to be connected with PAMAM via pH sensitive cis-aconitine anhydride (CA) to prepare bone-targeted micelle (DTX@ALN-PAMAM) to treat bone metastasis of lung cancer. Results: It was discovered that DTX@ALN-PAMAM released docetaxel (DTX) and ALN in pH-dependent manner. Besides, DTX@ALN-PAMAM showed high bind affinity with bone matrix, and quickly desorbed from bone matrix in weak acidic medium due to the rupture of cis-aconitamide bond between ALN and PAMAM. The in vitro results showed that DTX@ALN-PAMAM significantly enhanced the antitumor activity of DTX and decreased bone resorption through inhibiting the formation of osteoclasts in in-vitro 3D bone metastases model of lung cancer. In addition, DTX@ALN-PAMAM accumulated at bone metastases tissues for a relatively long time in tumor-bearing nude mice, which significantly reduced the bone resorption, relieved the pain response of tumor-bearing nude mice, and delayed the growth of bone metastases. Eventually, the therapeutic effect of DTX was improved on bone metastases of lung cancer. Conclusion: ALN modified PAMAM is a new and an effective platform for the treatment of bone metastasis of lung cancer.