Introduction Gold nanoparticles (GNPs) have drawn immense attention in cancer diagnosis and therapy during the past few years. Nanoparticles preferably leak and accumulate inside the tumour due to many reasons including high vascular density, increased vessel permeability, and defective lymphatic draining of tumours via a process called the enhanced permeability and retention (EPR) effect. Very small particles (<30 nm), although can enter the tumour tissue by the EPR effect, they also may leave it again by passive diffusion. This size-dependent cellular uptake thus limits the use of very small nanoparticles in cancer therapy. This study was conducted to improve the retention of small nanoparticles and overcome its size limitation by linking it to a noncoding DNA fragment. Material and methods A noncoding DNA fragment was amplified by PCR using a 5' thiol-labelled forward primer and an unmodified 3' reverse primer. After amplification, the PCR product was purified then conjugate to citrate stabilized10 nm GNPs. MCF-7 cells were treated with GNP-DNA conjugate using metafectene as a transfection agent for cytotoxicity studies. The GNP-DNA conjugate chemosensitization of MCF-7 cells to doxorubicin (Adriamycin ) was also tested. Results and discussions Treatment of MCF-7 cells with GNP-DNA conjugate resulted in a significant reduction in cell viability when compared to both control and unmodified GNP groups. The cell toxicity tests revealed that the conjugation of GNP with DNA lead to a 69.4-fold decrease in the IC 50 of GNP in MCF-7 cells. Furthermore, GNP-DNA conjugate showed a synergistic effect with doxorubicin leading to a significant reduction in cell viability at concentrations as low as 70 mM GNP-DNA and 1.6 mM doxorubicin. Conclusion The results of this study shed light on the marked effect of the modification of small GNP with DNA fragment on the effect of GNP in cancer cells and hence enables studying the effects of GNP size on cellular chemosensitivity without being restricted by GNP size-related differences in uptake efficiency. Introduction For Triple Negative Breast Cancers (TNBC) there are no effective specific targeted therapy readily available. CD44 is found overexpressed in many tumours, in particular TNBC, making this an attractive receptor for therapeutic targeting. Besides, Hsp90 inhibitors (Hsp90i) have been shown as promising molecules to treat cancer. Here we show our both drug delivery approaches to target TNBC. First, we describe a unique non-cationic liposome-based siRNA delivery system with a core composed of siRNA:protamine complexes and a shell designed for the active targeting of CD44-expressing cells using for the first time an anti-CD44 aptamer as targeting ligand. This was evaluated for the silencing of the luciferase reporter gene (luc2) in a TNBC breast cancer model in vitro and in vivo (orthotopically implanted) (Alshaer, 2015(Alshaer, , 2018. Secondly, we succeeded to use the inhibition of the chaperone Hsp90 against breast cancer. A promising Hsp90i derived from Novobiocin (...