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

Nanomedicine ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. 833-849 ◽  
Author(s):  
Shao-bo Bai ◽  
Ying Cheng ◽  
Dao-zhou Liu ◽  
Qi-feng Ji ◽  
Miao Liu ◽  
...  

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.

2019 ◽  
Author(s):  
Shao-bo Bai ◽  
Ying Cheng ◽  
Dao-zhou Liu ◽  
Qi-feng Ji ◽  
Miao Liu ◽  
...  

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.


2021 ◽  
Author(s):  
Cheng Cheng Zhang ◽  
Jingru Qin ◽  
Lu Yang ◽  
Zhiyao Zhu ◽  
Xinle Qian ◽  
...  

Bone metastasis of lung cancer and detailed mechanisms are still elusive, and the roles of exosomes derived from lung adenocarcinoma cells in this process have attracted much attention. In this study, we found that lung adenocarcinoma cell-derived exosomes (LCC-Exos) promoted osteogenesis and bone resorption in vitro. Furthermore, LCC-Exos target bone in vivo and promoted bone resorption in vivo. Mechanistically, LCC-Exosomal miR-328 promoted bone resorption by targeting Nrp2 and LCC-ExosmiR-328 Inhibitors inhibited bone resorption in vivo. Thus, LCC-Exosomal miR-328 promote osteoclastogenesis by targeting Nrp2 and LCC-ExosmiR-328 Inhibitors may serve as a potential nanomedicine for the treatment of bone metastasis.


2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Jianjiao Ni ◽  
Xiaofei Zhang ◽  
Juan Li ◽  
Zhiqin Zheng ◽  
Junhua Zhang ◽  
...  

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.


2013 ◽  
Vol 8 (12) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Sumit S Chourasiya ◽  
Eppakayala Sreedhar ◽  
K. Suresh Babu ◽  
Nagula Shankaraiah ◽  
V. Lakshma Nayak ◽  
...  

Bioactivity guided investigation of the DCM: MeOH (1:1) extract from the rhizomes of Alpinia galanga led to the isolation of phenylpropanoids (1–9) and their structures were established by 1H NMR, 13C NMR, IR and LC-MS/MS. These compounds have been evaluated for their in vitro anticancer activity against the human cancer cell lines A549 (lung cancer), Colo-205 (colon cancer), A431 (skin cancer), NCI H460 (lung cancer), PC-3 (prostate cancer), and HT-29 (colon cancer). Compounds 4 and 9 showed potent anticancer activity (ranging from 1.3–19.7 μg/mL) against all the tested cancer cell lines. In addition, an asymmetric synthesis of acetoxychavicol acetate (1) and trans-p-coumaryl alcohol (4) has been accomplished in six steps starting from readily available p-hydroxybenzaldehyde for the first time. Grignard reaction and Sharpless kinetic resolution reactions were utilized as the key steps to install the basic core.


2013 ◽  
Vol 5 (3) ◽  
pp. 707-710 ◽  
Author(s):  
XIAO-MAN XU ◽  
YI ZHANG ◽  
DAN QU ◽  
HONG-BO LIU ◽  
XIU GU ◽  
...  

MedChemComm ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 116-119 ◽  
Author(s):  
Fabrizio Olivito ◽  
Nicola Amodio ◽  
Maria Luisa Di Gioia ◽  
Monica Nardi ◽  
Manuela Oliverio ◽  
...  

In this work we synthesized and tested a series of unsaturated disulfides. Two compounds showed a promising anticancer activity in vitro on A549 lung cancer cells compared to the natural analogue.


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