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BSA-Stabilized Mesoporous Organosilica Nanoparticles Reversed Chemotherapy Resistance of Anaplastic Thyroid Cancer by Increasing Drug Uptake and Reducing Cellular Efflux.

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.

SUBMITTER: Han X

PROVIDER: S-EPMC7744685 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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BSA-Stabilized Mesoporous Organosilica Nanoparticles Reversed Chemotherapy Resistance of Anaplastic Thyroid Cancer by Increasing Drug Uptake and Reducing Cellular Efflux.

Han Xiao X Xu Xiaoquan X Tang Yuxia Y Zhu Feipeng F Tian Ying Y Liu Wei W He Doudou D Lu Guangming G Gu Yunfei Y Wang Shouju S

Frontiers in molecular biosciences 20201203

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 w ...[more]

PMID: 33344508

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Project description:Anaplastic thyroid carcinoma (ATC) is a highly aggressive tumor with a poor prognosis and a low median survival rate because of insufficient effective therapeutic modalities. Recently, mesoporous silica nanoparticles (MSNs) as a green non?toxic and safe nanomaterial have shown advantages to be a drug carrier and to modify the targeting group to the targeted therapy. To aim of the study was to explore the effects of MSNs co?loading with 17?allylamino?17?demethoxy?geldanamycin (17?AAG; HSP90 inhibitor) and 9?(6?aminopyridin?3?yl)?1?(3?(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin?2(1H)?one (Torin2; mTOR inhibitor) by targeting vascular endothelial growth factor receptor 2 (VEGFR2) on the viability of human anaplastic thyroid carcinoma FRO cells. The cytotoxicity of 17?AAG and Torin2 were analyzed by MTT assay. The possible synergistic antitumor effects between 17?AAG and Torin2 were evaluated by CompuSyn software. Flow cytometry was performed to assess the VEGFR2 targeting of (17?AAG+Torin2)@MSNs?anti?VEGFR2 ab and uptake by FRO cells. An ATC xenograft mouse model was established to assess the antitumor effect of (17?AAG+Torin2)@MSNs?anti?VEGFR2 ab in vivo. The results revealed that the combination of 17?AAG and Torin2 inhibited the growth of FRO cells more effectively compared with single use of these agents. Additionally, the synergistic antitumor effect appeared when concentration ratio of the two drugs was 1:1 along with total drug concentration greater than 0.52 µM. Furthermore, in an ATC animal model, it was revealed that the (17?AAG+Torin2)@MSNs?anti?VEGFR2 ab therapy modality could most effectively prolong the median survival time [39.5 days vs. 33.0 days (non?targeted) or 27.5 days (control)]. Compared to (17?AAG+Torin2)@MSNs, the (17?AAG+Torin2)@MSNs?anti?VEGFR2 ab could not only inhibit ATC cell growth but also prolong the median survival time of tumor?bearing mice in vivo and vitro more effectively, which may provide a new promising therapy for ATC.

Dataset Information

BSA-Stabilized Mesoporous Organosilica Nanoparticles Reversed Chemotherapy Resistance of Anaplastic Thyroid Cancer by Increasing Drug Uptake and Reducing Cellular Efflux.

Publications

BSA-Stabilized Mesoporous Organosilica Nanoparticles Reversed Chemotherapy Resistance of Anaplastic Thyroid Cancer by Increasing Drug Uptake and Reducing Cellular Efflux.

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