Journal
ACS NANO
Volume 10, Issue 11, Pages 9927-9937Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.6b03835
Keywords
tumor inhibition; apoptosis; selenium; nanoparticles; osteosarcoma
Categories
Funding
- NSFC [31430029, 81071263, 81461148032, 81471792, 30870624]
- National Key Technology Research and Development Program of China [2012BAI17B02]
- National Basic Research Program of China [2012CB933601]
- HUST Key Innovation Team Foundation for Interdisciplinary Promotion [2016JCTD101]
- Zhejiang Provincial Natural Science Foundation of China [LZ16E030001]
- National Institutes of Health [CA200504, CA195607, EB021339]
- National Science Foundation [CMMI-1234957]
- Department of Defense Office of Congressionally Directed Medical Research Programs [W81XWH-15-1-0180]
- Oklahoma Center for the Advancement of Science and Technology [HR14-160]
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Biocompatible tissue-borne crystalline nanoparticles releasing anticancer therapeutic inorganic elements are intriguing therapeutics holding the promise for both tissue repair and cancer therapy. However, how the therapeutic inorganic elements released from the lattice of such nanoparticles induce tumor inhibition remains unclear. Here we use selenium-doped hydroxyapatite nanoparticles (Se-HANs), which could potentially fill the bone defect generated from bone tumor removal while killing residual tumor cells, as an example to study the mechanism by which selenium released from the lattice of Se-HANs induces apoptosis of bone cancer cells in vitro and inhibits the growth of bone tumors in vivo. We found that Se-HANs induced apoptosis of tumor cells by an inherent caspase-dependent apoptosis pathway synergistically orchestrated with the generation of reactive oxygen species. Such mechanism was further validated by in vivo animal evaluation in which Se-HANs tremendously induced tumor apoptosis to inhibit tumor growth while reducing systemic toxicity. Our work proposes a feasible paradigm toward the design of tissue-repairing inorganic nanoparticles that bear therapeutic ions in the lattice and can release them in vivo for inhibiting tumor formation.
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