No 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.

Surface modification of nanocarriers enables selective attachment to specific molecular targets within a complex biological environment.

The electrokinetic sonic amplitude (ESA) is one of the most versatile techniques for deriving the zeta potential of nanoparticles before, during and after surface functionalization with different ligands, thus overcoming current limitations of well‐established electrophoretic measurement principles. We present a novel method for direct quantification of accessible hydroxide groups available on the surface of silica nanoparticles by the ESA effect, supported by simultaneous electrical conductivity measurements. Moreover, the in‐operando determination of varying zeta potential during addition of carboxylic acids demonstrate a profound way to quantify surface‐bound ligands, which still poses a challenge in following the surface modification of nanoparticles. In this study, phase pure cuboidal hematite particles were chosen as a model system with an initial zeta potential between +50 and +55 mV in ethanol. Using both citric acid and 10‐undecynoic acid as surface‐modifiers, the correlation between the degree of surface functionalization and zeta potential was investigated. The decrease of zeta potential of hematite particles during the titration of 10‐undecynoic acid or citric acid could be directly correlated to a successful surface functionalization in contrast to a surface protonation, which would be expected in case of both carboxylic acids. Furthermore, the addition of 10‐undecynoic acid led to a stabilization effect on the zeta potential of cuboidal hematite particles. These results highlight the hitherto unexplored potential of ESA techniques as a quantification method in nanoparticle surface modification.

Site-specific delivery using functionalized nanocarriers is in high demand in imaging applications of modern clinical research.