Cyclodextrin Dimers Functionalized with Biotin as Nanocapsules for Active Doxorubicin Delivery Against MCF-7 Breast...

Area of Science:

• Bioconjugation Chemistry
• Nanomedicine
• Cancer Biology

Background:

• Cyclodextrin dimers offer enhanced stability for encapsulating poorly water-soluble drugs.
• Biotinylation of nanocarriers can facilitate targeted drug delivery via the Sodium-dependent Multivitamin Transporter (SMVT).
• Understanding drug resistance mechanisms, like those involving ABCG2, is crucial for effective cancer therapy.

Purpose of the Study:

• To design and synthesize novel beta- and gamma-cyclodextrin dimers functionalized with biotin.
• To evaluate these bioconjugates as targeted delivery systems for doxorubicin in cancer cells.
• To investigate the role of biotin targeting and related gene expression in doxorubicin efficacy.

Main Methods:

• Synthesis of biotinylated cyclodextrin dimers.
• Evaluation of Sodium-dependent Multivitamin Transporter (SLC5A6) expression in human cell lines (MCF-7 selected).
• Analysis of transcript levels for Holocarboxylase Synthetase (HLCS), Biotinidase (BTD), and ABCG2 transporter.
• In vitro assessment of doxorubicin-loaded dimer cytotoxicity in MCF-7 cells.

Main Results:

• Successfully designed and synthesized biotinylated beta- and gamma-cyclodextrin dimers.
• Identified MCF-7 cells as a suitable model due to SLC5A6 expression.
• Quantified expression of genes related to biotin metabolism and doxorubicin resistance.
• Demonstrated the antiproliferative effect of doxorubicin-loaded dimers, influenced by the biotin moiety.

Conclusions:

• Biotinylated cyclodextrin dimers show promise as targeted doxorubicin delivery systems.
• The SMVT receptor plays a key role in enhancing drug uptake and efficacy.
• Further research into these bioconjugates could lead to novel cancer therapeutic strategies.