Receptor-Mediated In Vivo Targeting of Breast Cancer Cells with 17α-Ethynylestradiol-Conjugated Silica-Coated Gold Nanoparticles

Abstract

Efficient therapies for breast cancer remain elusive because of the lack of strategies for targeted transport and receptor-mediated uptake of synthetic drug molecules by cancer cells. Conjugation of nanoparticles (NPs) with active targeting ligands enabling selective molecular recognition of antigens expressed on the surface of cancer cells is promising for localization and treatment of malignant cells. In this study, covalent attachment of synthetic estrogen 17α-ethynylestradiol on the silica (SiO2) shell of silica-gold NPs (SiO2@Au) was undertaken to improve the cancer-targeting ability of the nano-biotags. Chemical and structural analysis of the bioconjugates examined in solution (UV–vis and ξ-potential) and solid state (Fourier transform infrared spectroscopy, X-ray diffractometry, and transmission electron microscopy) confirmed the identity of the carrier particles and surface-bound ligands. The mesoporous silica shell served as a reservoir for anticancer drugs (doxorubicin and quercetin) and to facilitate covalent attachment of receptor molecules by click chemistry protocols. The chemoselective recognition between the nanoconjugates and cell membranes was successfully demonstrated by the accumulation of nanoprobes in the tumor tissue of mice with subcutaneous breast cancer, whereas healthy cells were unaffected. The drug release studies showed sustained release kinetics over several weeks. These findings elaborate the exceptional selectivity and potential of estrogen-coated nano-biolabels in efficient diagnosis and detection of breast cancer cells.

Click functionalized biocompatible gadolinium oxide core-shell nanocarriers for imaging of breast cancer cells

“…The diversion of FC and ZFC curves starts already at 270 K, and agree with the high temperature maximum of both curves. Although the signal is relatively weak, the behavior is mimicking that of pure Fe 3 O 4 NPs, 26 however, there is an additional "tail" at lower temperatures in both FC and ZFC curves, indicating the presence of the paramagnetic Gdmoments. Moreover, there is no clear blocking temperature, as was observed at about 120 K for the composite SiO 2 @Fe 3 O 4 material without the Gd 2 O 3 shell (Fig.…”

“…The efficiency of the surface-functionalized nanocarriers in biological systems is inuenced by the physical and chemical nature of the surface-attached groups. 26,46,47 Since both carriers contain a thin gadolinium oxide layer, only the multilayer Gd 2 O 3 @SiO 2 @Fe 3 O 4 with cube-based nanocarriers were extended for chemical conjugation strategies to prove the conjugation concept. The Gd 2 O 3 @SiO 2 @Fe 3 O 4 were modied with APTMS molecules to offer free amino (-NH 2 ) groups.…”

Active Targeting Gold Nanoparticle for Chemotherapy Drug Delivery: A Review

“…• Enhance uptake/internalization on targeted cell 34 • Reduce toxicity in normal cells 19,35 • Possibility of immunogenic response 38…”

“…EE-AuNP also accumulated in tumor tissue whereby health cells were unaffected. 35 Antiandrogen ligands (α-Bicalutamide and β-Bicalutamide) conjugated with AuNP via PEG -SH showed a reduction in cancer growth and progression. Antiandrogen conjugated AuNP selectively stimulated G-protein coupled receptor (GPRC6A) multivalent affinity and accumulated in hormone-insensitive and chemotherapy-resistant prostate cancer cells.…”

18F-Labeled magnetic nanovectors for bimodal cellular imaging

“…metals, oxides, and lanthanide-doped) have gained significant attention in the field of biomedical imaging. [1][2][3][4][5][6][7][8][9][10] They are mainly used as contrast agents [11][12][13][14][15][16] following a significant function in numerous emerging applications such as photodynamic therapy, hyperthermia based cancer treatments or magnetic resonance imaging (MRI). 17 Magnetic NPs are favored as MRI contrast agents 18 due to their low cytotoxicity in the human body as validated by various clinical studies.…”