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.

ALA/Ag2S/MnO2 Hybrid Nanoparticles for Near-Infrared Image-Guided Long-Wavelength Phototherapy of Breast Cancer

“…Albumin protein, in general, is proven to have a potential in the active targeting of cancer cells, as it binds to several specific receptors on the cell membrane, including glycoproteins (Gp18, Gp30, and Gp60) and secreted protein acidic rich in cysteine (SPARC), which is responsible for recycling and transcytosis. , These glycoproteins are highly overexpressed in endothelial cells around tumor tissues, allowing BSA to accumulate in tumor sites. Furthermore, as the cancer cells’ metabolism rate is higher than that of the healthy cells, nutrients such as albumin protein are internalized faster and in higher amounts, therefore facilitating the internalization of albumin-coated NPs . Zhang et al coated mesoporous silica NPs (MSN) loaded with the anti-cancer drug doxorubicin (DOX) with BSA to obtain a biocompatible and stable drug delivery system and observed a high uptake of NPs, which enabled efficient cell imaging and drug delivery .…”

Nanoparticles: Promising Auxiliary Agents for Diagnosis and Therapy of Thyroid Cancers

“…Such MSNs loaded with doxorubicin were more successful than the melaninlinked NPs produced from dopamine hydrochloride. While the melanin-linked NPs had a doxorubicin loading capacity of 20%, the mesoporous organic silica particles reached 47.02% [75,76]. Coating MSNs with bovine serum albumin stabilized the doxorubicin loading and induced uptake by drug-sensitive anaplastic thyroid cancer HTh74 cells but not by human HaCaT keratinocytes.…”

Counterion Tuning of Near-Infrared Organic Salts Dictates Phototoxicity to Inhibit Tumor Growth

“…Albumin is reported to have increased tumor accumulation due to upregulated albumin catabolism that fuels cancer growth . Recent studies report that mesochlorinated cyanines can covalently bind to albumin and that cyanine albumin adducts accumulate within the tumor interstitium. , Albumin is a commonly used targeting moiety for chemotherapeutics and nanomaterials; thus, albumin conjugation may contribute to the tumor-targeting ability of cyanine dyes. , To assess the mechanisms of tumor targeting, biodistribution, and potential translatability of our findings to additional cancers and preclinical models, we also characterize uptake mediated by mouse Oatps and albumin in vitro .…”

“… 31 , 32 Albumin is a commonly used targeting moiety for chemotherapeutics and nanomaterials; thus, albumin conjugation may contribute to the tumor-targeting ability of cyanine dyes. 33 , 34 To assess the mechanisms of tumor targeting, biodistribution, and potential translatability of our findings to additional cancers and preclinical models, we also characterize uptake mediated by mouse Oatps and albumin in vitro .…”