Synthesis and biological evaluation of theranostic Trastuzumab–SN38 conjugate for Near-IR fluorescence imaging and targeted therapy of HER2+ breast cancer

Shifting the Antibody–Drug Conjugate Paradigm: A Trastuzumab-Gold-Based Conjugate Demonstrates High Efficacy against Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Mouse Model

“…To assess the cytotoxicity profile of the Au payloads and their corresponding ADCs, we selected several human breast cancer cell lines expressing different levels of HER2, such as MCF-7 (endogenous HER2 expression), BT-474 (HER2 overexpression), and SKBR-3 (HER2 overexpression). Human cells that do not overexpress HER2, such as triple-negative breast cancer (MDA-MB-231) and noncancerous breast cells (MCF-10A), were chosen to assess selectivity. , …”

“…These doses were selected based on MTD studies with an anti-HER2 antibody and anti-HER2-based ADCs as well as doses for MTD studies for auranofin and other gold­(I)-phosphane compounds when dosed daily or every other day. Since our study was designed to assess the toxicity of ADCs which are typically dosed weekly, ,, these treatment doses and regimen were selected. Mice were intravenously injected with each dose of the drug once a week for 4 weeks.…”

“…Human cells that do not overexpress HER2, such as triplenegative breast cancer (MDA-MB-231) and noncancerous breast cells (MCF-10A), were chosen to assess selectivity. 29,58 We also include the cell viability for carboxylic acid precursors (1a, CREF and 1b, FIN) and auranofin (which contains the [Au(PEt 3 )] fragment present in Thio-2b and is being evaluated in different cancer clinical trials). 40,41 We routinely use auranofin in our cell viability studies of compounds that contain gold.…”

Effective synthesis, development and application of a highly fluorescent cyanine dye for antibody conjugation and microscopy imaging

“…In spite of the fact that the relevance of cyanine conjugated antibodies is obviously high, recently, only a few examples have been published (Table S1†). 30–35…”

“…29 In spite of the fact that the relevance of cyanine conjugated antibodies is obviously high, recently, only a few examples have been published (Table S1 †). [30][31][32][33][34][35] In this regard, and as a continuation of our interest in the design and synthesis of novel asymmetric dyes [36][37][38][39][40][41][42] and antibody modification, we herein describe the development of a novel fluorescent cyanine dye. 37,43,44 The strengths of our novel asymmetric cyanine are as follows: first, we increased solubility by introducing a positively charged ionic core; second, we improved its photophysical properties, in particular increasing the Stokes shift by 25 nm, which improved image quality and reduced self-absorption, achieving an excitation maximum at the desirable 633 nm wavelength, and an improving photostability; and third, we added an azide-containing linker that enables its application in azide-alkyne click reactions, which results in an optimal fluorophore-antibody ratio.…”