Publication:
Doxorubicin-loaded micelle targeting MUC1: A potential therapeutic for MUC1 triple negative breast cancer treatment

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Issued Date

2018

Resource Type

Article

File Type

application/pdf

ISSN

15672018

DOI

10.2174/1567201814666170712122508

Other identifier(s)

2-s2.0-85045011068

Rights Holder(s)

มหาวิทยาลัยศรีนครินทรวิโรฒ

Bibliographic Citation

Current Drug Delivery. Vol 15, No.3 (2018), p.406-416

Suggested Citation

Khondee S., Chittasupho C., Tima S., Anuchapreeda S. Doxorubicin-loaded micelle targeting MUC1: A potential therapeutic for MUC1 triple negative breast cancer treatment. Current Drug Delivery. Vol 15, No.3 (2018), p.406-416. doi:10.2174/1567201814666170712122508 Retrieved from: https://hdl.handle.net/20.500.14740/3957

Title

Doxorubicin-loaded micelle targeting MUC1: A potential therapeutic for MUC1 triple negative breast cancer treatment

Author(s)

Khondee S.
 Chittasupho C.
 Tima S.
 Anuchapreeda S.

Abstract

Background: Triple negative breast cancer (TNBC) is an aggressive disease associated with poor prognosis and lack of validated targeted therapy. Thus chemotherapy is a main adjuvant treatment for TNBC patients, but it associates with severe toxicities. For a better treatment outcome, we developed an alternative therapeutic, doxorubicin (DOX)-loaded micelles targeting human mucin1 protein (MUC1) that is less toxic, more effective and targeted to TNBC. Methods: From many candidate peptides, QNDRHPR-GGGSK (QND) and HSQLPQV-GGGSK (HSQ) were identified computationally, synthesized and purified using solid phase peptide synthesis and semipreparative HPLC. The peptides showed significant high binding to MUC1 expressing cells using a fluorescent microscope. The peptides were then conjugated on pegylated octadecyl lithocholate copolymer. DOX-encapsulated micelles were formed through self-assembly. MUC1-targeted micelles were characterized using dynamic light scattering (DLS) and Transmission Electron Microscopy (TEM). Drug entrapment efficiency was examined using a microplate reader. Cytotoxicity, binding, and uptake were also investigated. Results: Two types of DOX-loaded micelles with different targeting peptides, QND or HSQ, were developed. DOX-loaded micelles were spherical in shape with average particle size around 300-320 nm. Drug entrapment efficiency of untargeted and targeted DOX micelles was about 71-93%. Targeted QND-DOX and HSQ-DOX micelles exhibited significantly higher cytotoxicity compared to free DOX and untargeted DOX micelles on BT549-Luc cells. In addition, significantly greater binding and uptake were observed for QND-DOX and HSQ-DOX micelles on BT549-Luc and T47D cells. Conclusion: Taken together, these results suggested that QND-DOX and HSQ-DOX micelles have a potential application in the treatment of TNBC-expressing MUC1. © 2018 Bentham Science Publishers.

Subject(s)

Doxorubicin
 Mucin 1
 Antineoplastic antibiotic
 Doxorubicin
 Drug carrier
 MUC1 protein, human
 Mucin 1
 Peptide
 Article
 Breast cancer cell line
 Cell viability
 Cytotoxicity
 Drug binding
 Drug delivery system
 Drug efficacy
 Drug mechanism
 High performance liquid chromatography
 Human
 Human cell
 Micelle
 Particle size
 Peptide synthesis
 Photon correlation spectroscopy
 Priority journal
 Protein targeting
 Transmission electron microscopy
 Triple negative breast cancer
 Cell survival
 Drug effect
 Drug release
 Metabolism
 Micelle
 Tumor cell line
 Antibiotics, Antineoplastic
 Cell Line, Tumor
 Cell Survival
 Doxorubicin
 Drug Carriers
 Drug Liberation
 Humans
 Micelles
 Mucin-1
 Peptides
 Triple Negative Breast Neoplasms

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URI

https://hdl.handle.net/20.500.14740/3957

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Scopus: Year 1983-2021

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