Targeted and Controllable Dual Photothermo-chemotherapy for Breast Cancer Based on Multifunctional Gold Nanoparticles




Wang, Lijun

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The overall objective of this research was to design and develop gold nanoparticles-based multifunctional therapeutic nanocomposite for breast cancer treatment. This nanocomposite uses gold nanorods (GNRs) and gold nanoclusters (GNCs) to administrate a combination photothermal and Doxorubicin (Doxo)-based therapy. GNRs of various sizes were fabricated in a single or binary hexadecyltrimethylammonium bromide (CTAB) system using the seed-mediated method. GNRs with a mean diameter at ~10nm which showed the highest photothermal effect were selected for subsequent experiments to develop the nanocomposite. To reduce the toxicity from CTAB, GNRs were modified and functionalized with sodium citrate. GNCs were synthesized in bovine serum albumin (BSA), integrated onto GNRs via layer-by-layer (LbL) assembly, and immobilized onto GNRs by glutaraldehyde (GLA) through crosslinking with the lysine residues in BSA. The "softgel-like" structure not only provided binding sites for Doxo via electrostatic interactions, but also increased the structural stability of the nanocomposite. Also, the presence of GNCs made the nanocomposite emit intensive fluorescence ranging from ~520 to 700nm. To increase cellular internalization, hyaluronic acid (HA) was employed as the targeting moiety spreading on the surface of the nanocomposite. Finally, the safety and therapeutic efficacy of the nanocomposite was evaluated on monolayer and three-dimensional cellular culture systems. The nanocomposite exhibited excellent stability in vitro and had a pH-and near infrared (NIR) dual-responsive drug release behavior. In-vitro studies showed that the nanocomposite was efficiently internalized by breast cancer MDA-MB-231 cells and remarkedly reduced cellular viability under NIR irradiation. These results demonstrated a great potential of the developed nanocomposite for targeted breast cancer therapy.


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Biomedical Engineering