Original ArticleSelenium-doped calcium phosphate biomineral reverses multidrug resistance to enhance bone tumor chemotherapy
Graphical Abstract
Selenium-doped calcium phosphate (Se-CaP) biominerals with high biocompatibility, biodegradability and pH-sensitive drug release properties have been prepared, which not only serve as effective drug-carrier to enhance the uptake of Doxorubicin, but also synchronously induce the apoptosis of osteosarcoma in vitro and in vivo. With the similar chemical properties to the inorganic component of hard tissue, Se-CaP biomineral may be a promising candidate in treating bone tumor with MDR characteristic.
Section snippets
Materials and methods
Se-CaPs with Se/(Se + P) molar ratios of 0, 0.005, 0.01, 0.03, 0.09 and 0.15 were synthesized through a microwave-assisted hydrothermal method using adenosine 5′-triphosphate disodium salt hydrate (C10H14N5O13P3Na2·xH2O, Na2ATP) (Sigma-Aldrich Co., US) as the organic phosphorus source. The obtained products were labeled as control, Se0.005-CaP, Se0.01-CaP, Se0.03-CaP, Se0.09-CaP and Se0.15-CaP. The as-prepared different Se-CaPs samples were characterized with X-ray powder diffraction (XRD),
Synthesis and characterization
A series of CaP and Se-CaP microspheres were synthesized using Na2ATP as a phosphorus source, under a microwave-assisted hydrothermal reaction at 110 °C for 10 min (Figure 1, A). Scanning electron microscopy (SEM, Figure 1, B, C) and transmission electron microscopy (TEM, Figure 1, E, F) were used to characterize the morphologies of CaP and Se-CaP products, which displayed a microsphere structure with diameters of approximately 200 nm and 150 nm, respectively. After the addition of SeO32− in
Discussion
To overcome MDR, numerous innovative therapeutic strategies have been designed, and among them, NDDS has achieved great success and drawn much attention.30 One of the most inspiring results is the pegylated liposomal doxorubicin, which has been applied in clinical treatments for cancer therapy.31 Pegylated liposomal doxorubicin has also been reported to be effective for advanced sarcomas after the failure of conventional agents with modest toxicity.32,33
Most NDDSs are designed to facilitate
Declaration of competing interest
There are no conflicts to declare.
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The financial support from the National Natural Science Foundation of China (81572630, 81872174, 31771081), the Science and Technology Commission of Shanghai Municipality (18ZR1445100, 19XD1402900, 19JC1414300) and S&T Innovation 2025 Major Special Programme of Ningbo (2018B10040) is gratefully acknowledged.
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These authors contributed equally to this work and should be considered co-first authors.