作者
Archana Swami, Michaela R Reagan, Pamela Basto, Yuji Mishima, Nazila Kamaly, Siobhan Glavey, Sufeng Zhang, Michele Moschetta, Dushanth Seevaratnam, Yong Zhang, Jinhe Liu, Masoumeh Memarzadeh, Jun Wu, Salomon Manier, Jinjun Shi, Nicolas Bertrand, Zhi Ning Lu, Kenichi Nagano, Roland Baron, Antonio Sacco, Aldo M Roccaro, Omid C Farokhzad, Irene M Ghobrial
发表日期
2014/7/15
期刊
Proceedings of the National Academy of Sciences
卷号
111
期号
28
页码范围
10287-10292
出版商
National Academy of Sciences
简介
Bone is a favorable microenvironment for tumor growth and a frequent destination for metastatic cancer cells. Targeting cancers within the bone marrow remains a crucial oncologic challenge due to issues of drug availability and microenvironment-induced resistance. Herein, we engineered bone-homing polymeric nanoparticles (NPs) for spatiotemporally controlled delivery of therapeutics to bone, which diminish off-target effects and increase local drug concentrations. The NPs consist of poly(d,l-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and bisphosphonate (or alendronate, a targeting ligand). The engineered NPs were formulated by blending varying ratios of the synthesized polymers: PLGA-b-PEG and alendronate-conjugated polymer PLGA-b-PEG-Ald, which ensured long circulation and targeting capabilities, respectively. The bone-binding ability of Ald-PEG-PLGA NPs was investigated by …
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A Swami, MR Reagan, P Basto, Y Mishima, N Kamaly… - Proceedings of the National Academy of Sciences, 2014