An ideal therapeutic antibody-oligonucleotide conjugate (AOC) would be a uniform construct, contain a maximal oligonucleotide (ON) payload, and retain the antibody (Ab)-mediated binding properties, which leads to an efficient delivery of the ON cargo to the site of therapeutic action. Herein, [60]fullerene-based molecular spherical nucleic acids (MSNAs) have been site-specifically conjugated to antibodies (Abs), and the Ab-mediated cellular targeting of the MSNA-Ab conjugates has been studied. A well-established glycan engineering technology and robust orthogonal click chemistries yielded the desired uniform MSNA-Ab conjugates (MW ∼ 270 kDa), with an oligonucleotide (ON):Ab ratio of 24:1, in 20-26% isolated yields. These AOCs retained the antigen binding properties (Trastuzumab's binding to human epidermal growth factor receptor 2, HER2), studied by biolayer interferometry. In addition, Ab-mediated endocytosis was demonstrated with live-cell fluorescence and phase-contrast microscopy on BT-474 breast carcinoma cells, overexpressing HER2. The effect on cell proliferation was analyzed by label-free live-cell time-lapse imaging.