Abstract
Anaplastic thyroid cancer (ATC) is a highly aggressive and the most lethal type of thyroid cancer. The standard-of-care for unresectable ATC is radiotherapy and chemotherapy, usually based on doxorubicin (Dox). However, most patients develop resistance shortly after treatment. To overcome the drug resistance, we synthesized the mesoporous organosilica nanoparticles (MONPs) loaded with Dox and stabilized the nanocomposites by bovine serum albumin (BSA). The surface area and pore volume of MONPs were 612.653 m2/g and 0.589 cm3/g. The loading capacity of Dox-MONPs reached 47.02%. Compared to Dox-MONPs and free Dox, BSA-Dox-MONPs had more durable tumor-killing power on both drug-sensitive cell line HTh74 and drug-resistant cell line HTh74R. The cellular uptake of BSA-Dox-MONPs was 28.14 and 65.53% higher than that of Dox-MONP in HTh74 and HTh74R. Furthermore, the BSA coating decreased the efflux rate of nanocomposites in HTh74 (from 38.95 to 33.05%) and HTh74R (from 43.03 to 32.07%). In summary, BSA-Dox-MONPs reversed the chemotherapy resistance of ATC cells via increased drug uptake and inhibited drug efflux, offering a promising platform for the treatment of chemo-resistant ATC.
Highlights
Anaplastic thyroid cancer (ATC) has lately received considerable attention for reduced median survival rate and high invasion
After bovine serum albumin (BSA) coating, the zeta potential of BSA-Dox-mesoporous organosilica nanoparticles (MONPs) plummeted to −21.70 ± 0.81 mV because the BSA were negatively charged (Figure 4B). These results suggested the Dox and BSA was successfully loaded on the MONPs
It is worth noting that the BSA coating reduced the efflux rate of MONPs, especially in drug-resistant HTh74R. These results indicated BSA-Dox-MONPs reversed the resistance of HTh74R cells by enhancing drug uptake and inhibiting drug efflux
Summary
Anaplastic thyroid cancer (ATC) has lately received considerable attention for reduced median survival rate and high invasion. The median survival of patients is no longer than 5 months, and the two-year survival rate is less than 15% (Molinaro et al, 2017). Combination treatment, including extensive resection and adjuvant chemo-radiotherapy, is recommended (Haddad et al, 2018). Doxorubicin (Dox) is the only chemo-drug suggested, the resistance to Dox is collective in ATC, leading to a worse prognosis (Haddad et al, 2018). A critical mechanism behind the Dox resistance is the excessive efflux of chemotherapy drugs (Zinzi et al, 2014; Davis et al, 2015).
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