Bone-targeted PAMAM nanoparticle to treat bone metastases of lung cancer.

Aim: To prepare pH-sensitive nanoparticle composed of alendronate (ALN) and poly(amidoamine) (PAMAM) to treat bone metastases of lung cancer. Methods: The solvent evaporation method was used to prepare docetaxel (DTX)-loaded ALN-PAMAM nanoparticles (DTX@ALN-PAMAM). Results: The in vitro results showed DTX@ALN-PAMAM significantly enhanced the anticancer activity of DTX and inhibited the formation of osteoclasts. DTX@ALN-PAMAM concentrated at bone metastasis site in mice, which resulted in the suppression of bone resorption, pain response and growth of bone metastases. Eventually, the therapeutic effect of DTX on bone metastases of lung cancer was obviously improved. Conclusion: ALN modified PAMAM nanoparticle could be an effective platform for the treatment of bone metastases of lung cancer.

Osteoclasts and tumor cells dual targeting nanoparticle to treat bone metastases of lung cancer.

Bone is one of the prone metastatic sites of lung cancer. Osteoclast plays an important role in bone resorption and the growth of bone metastases of lung cancer. In order to treat bone metastases of lung cancer, we reported a docetaxel (DTX)-loaded nanoparticle, DTX@AHP, which could target dually at osteoclasts and bone metastatic tumor cells. The in vitro drug release from DTX@AHP exhibited pH and redox responsive characteristics. DTX@AHP displayed high binding affinity with bone matrix. In addition, DTX@AHP significantly inhibited the differentiation of RAW264.7 into osteoclast and effectively inhibited the proliferation of osteoclasts and tumor cells in in-vitro 3D bone metastases model of lung cancer. DTX@AHP could accumulate in bone metastases sites in vivo. Consequently, DTX@AHP not only markedly inhibited the growth of bone metastases of lung cancer but also reduced osteolysis in tumor-bearing mice. DTX@AHP exhibited great potential in the treatment of bone metastases of lung cancer.