Kinetic Rate Equations in Integrated form for Single-Step Reactions Involving Different Types of Reactant

Ray, Aniruddha; Mandal, Bholanath

doi:10.3184/146867808x340564

Cited by 1 publication

(1 citation statement)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reaction progress was calculated based on the second-order kinetics of two starting materials, rate = k [A][B], A = N 3 or Tz, B = DBCO or TCO. The rate law was derived according to the previously published work . Based on our conjugation conditions, we translated the obtained LAR to the concentration of DBCO or TCO in the conjugation mixture to be around 50 μM.…”

Section: Methodsmentioning

confidence: 99%

Optimizing Conjugation Chemistry, Antibody Conjugation Site, and Surface Density in Antibody–Nanogel Conjugates (ANCs) for Cell-Specific Drug Delivery

Prachyathipsakul

Huynh

et al. 2023

Bioconjugate Chem.

View full text Add to dashboard Cite

Targeted delivery of therapeutics using antibody–nanogel conjugates (ANCs) with a high drug-to-antibody ratio has the potential to overcome some of the inherent limitations of antibody–drug conjugates (ADCs). ANC platforms with simple preparation methods and precise tunability to evaluate structure–activity relationships will greatly contribute to translating this promise into clinical reality. In this work, using trastuzumab as a model antibody, we demonstrate a block copolymer-based ANC platform that allows highly efficient antibody conjugation and formulation. In addition to showcasing the advantages of using an inverse electron-demand Diels–Alder (iEDDA)-based antibody conjugation, we evaluate the influence of antibody surface density and conjugation site on the nanogels upon the targeting capability of ANCs. We show that compared to traditional strain-promoted alkyne–azide cycloadditions, the preparation of ANCs using iEDDA provides significantly higher efficiency, which results in a shortened reaction time, simplified purification process, and enhanced targeting toward cancer cells. We also find that a site-specific disulfide-rebridging method in antibodies offers similar targeting abilities as the more indiscriminate lysine-based conjugation method. The more efficient bioconjugation using iEDDA allows us to optimize the avidity by fine-tuning the surface density of antibodies on the nanogel. Finally, with trastuzumab-mertansine (DM1) antibody–drug combination, our ANC demonstrates superior activities in vitro compared to the corresponding ADC, further highlighting the potential of ANCs in future clinical translation.

show abstract

Section: Methodsmentioning

confidence: 99%