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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.

Background Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. Paris saponin VII (PSVII) could not only inhibit the proliferation of colon cancer cells but also effectively induce apoptosis of drug-resistant colon cancer cells and reduce the metastasis of drug-resistant colon cancer cells as well. However, PSVII was insoluble in water and fat. It displayed no selective distribution in body and could cause severe hemolysis. Herein, colon cancer targeting calcium phosphate nanoparticles were developed to carry PSVII to treat drug-resistant colon cancer. Results PSVII carboxymethyl-β-cyclodextrin inclusion compound was successfully encapsulated in colon cancer targeting calcium phosphate nanoparticles (PSVII@MCP-CaP) by using modified citrus pectin as stabilizer agent and colon cancer cell targeting moiety. PSVII@MCP-CaP significantly reduced the hemolysis of PSVII. Moreover, by specific accumulating in orthotopic drug-resistant colon cancer tissue, PSVII@MCP-CaP markedly inhibited the growth of orthotopic drug-resistant colon cancer in nude mice. PSVII@MCP-CaP promoted the apoptosis of drug-resistant colon cancer cells through mitochondria-mediated apoptosis pathway. Moreover, PSVII@MCP-CaP significantly inhibited the invasion and migration of drug-resistant colon cancer cells by increasing E-cadherin protein expression and reducing N-cadherin and MMP-9 protein expression. Conclusion PSVII@MCP-CaP has great potential in the treatment of drug-resistant colon cancer. This study also explores a new method to prepare active targeting calcium phosphate nanoparticles loaded with a fat and water insoluble compound in water. Graphical Abstract

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.