Camouflaged, activatable and therapeutic tandem bionanoreactors for breast cancer theranosis

[Display omitted] The one-pot cascade reaction of naturally occurring enzymes is exciting for highly selective complex reaction and biodegradable approaches. Tamoxifen is the main drug against breast cancer for decades and induces an anticancerous effect upon metabolic activation by cytochrome P450...

Full description

Saved in:
Bibliographic Details
Published in:Journal of colloid and interface science 2020-11, Vol.580, p.365-376
Main Authors: Chauhan, Kanchan, Sengar, Prakhar, Juarez-Moreno, Karla, Hirata, Gustavo A., Vazquez-Duhalt, Rafael
Format: Article
Language:English
Subjects:
Breast tumors
Cascade biocatalysis
Theranosis
Therapeutic nanoreactors
Tumor-activatable
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:[Display omitted] The one-pot cascade reaction of naturally occurring enzymes is exciting for highly selective complex reaction and biodegradable approaches. Tamoxifen is the main drug against breast cancer for decades and induces an anticancerous effect upon metabolic activation by cytochrome P450 (CYP450). Herein, bi-enzymatic nanoreactors (NRs) are developed as a multimodality platform for smart action against breast tumors. CYPBM3 of Bacillus magaterium (CYP) is co-confined with glucose oxidase (GOx) where GOx produces H2O2 in the presence of glucose that elicits the CYP-mediated transformation of tamoxifen. The scintillating and mesoporous LaF3:Tb as nanocarrier showed advantages like a wide range of pore size and positive surface charge for efficient loading of enzyme couple, while the smallest pores were available for substrate/product diffusion. The obtained NRs were camouflaged with human serum albumin (HSA) to overcome premature enzyme leaching and provide active stealth properties. The nanocomposite was characterized for physicochemical properties and glucose-mediated sequential catalysis. The in vitro studies demonstrated the cell internalization of NRs in both ER+ and triple-negative breast cancer cell lines and showed significant cytotoxicity. The developed NRs not only improve the outcomes of endocrine therapy in ER+ cells but also synergistically act with oxidation therapy for enhanced therapeutic effect. Importantly, inhibition of triple-negative cells was also achieved. Thus, the development of the new multimodal nanomedicine of the present work should afford new tools towards the theranosis of breast cancer with minimized adverse effects.
ISSN:0021-9797
1095-7103
DOI:10.1016/j.jcis.2020.07.043