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首页> 外文期刊>ACS applied materials & interfaces >Displacement Affinity Release of Antibodies from Injectable Hydrogels
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Displacement Affinity Release of Antibodies from Injectable Hydrogels

机译：从注射水凝胶中释放抗体的位移亲和力

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摘要

Current methods to tune release rates of therapeutic antibodies (Abs) for local delivery are complex and routinely require bioconjugations that may reduce Ab bioactivity. To rapidly tune release profiles of bioactive Abs, we developed a biophysical interaction system within a neutravidin modified poly(carboxybetaine) hydrogel (pCB-NT) that tunes release rates of desthiobiotinylated Abs (D-Abs) using a constant hydrogel and D-Ab combination. Herein, we delivered desthiobiotinylated bevacizumab (D-Bv), a recombinant humanized monoclonal IgG1 Ab for antiangiogenic cancer therapies. D-Bv's high affinity for pCB-NT (K-D 7.8 x 10(-10) M; t(1/2) similar to 2 h) produces a slow D-Bv release rate (similar to 5 ng day(-1)) that is increased by the dissolution of hydrogel encapsulated biotin derivative pellets, which displaces D-Bv from pCB-NT binding sites. In contrast to traditional affinity systems, displacement affinity release of Abs (DARA) does not require Ab or hydrogel modifications for each unique release rate. D-Bv release rates were tuned by simply altering the total biotin derivative concentration; the effective first-order (k(eff)) and mass per day release rates were tuned 25- and 8-fold, respectively. Local surface plasmon resonance (LSPR) and biolayer interferometry (BLI) confirmed the D-Bv binding affinity for the corresponding ligand and Fc receptor, demonstrating that the biophysical interaction system is amenable to anticancer Abs for receptor or cytokine blockade and immune cell recruitment to cancer cells.
机译：目前对局部递送的治疗性抗体（ABS）的释放速率的目的方法复杂，并且常规需要可能降低AB生物活性的生物缀合物。为了快速调整生物活性腹肌的释放型材，我们在中性化素改性的聚（羧基脲）水凝胶（PCB-NT）中开发了一种生物物理相互作用系统，其使用恒定的水凝胶和D-AB组合调节失效的ABS（D-ABS）的释放速率。在此，我们递送了抗菱噻吩基化的贝伐单抗（D-BV），一种用于抗血管生成癌疗法的重组人源化单克隆IgG1 AB。 D-BV对PCB-NT的高亲和力（KD 7.8 x 10（-10）m; t（1/2）类似于2 h），产生缓慢的D-BV释放速率（类似于5 ng（-1））通过水凝胶包封的生物素衍生物颗粒的溶解来增加，其从PCB-NT结合位点移植D-BV。与传统的亲和系统相比，ABS（DARA）的位移亲和力释放不需要针对每个独特的释放速率进行AB或水凝胶修饰。通过简单地改变总生物素衍生物浓度来调整D-BV释放速率;每天释放率的有效一阶（K（Eff））和质量分别调整25-倍和8倍。局部表面等离子体共振（LSPR）和Biolayer干涉测量（BLI）证实了对应配体和Fc受体的D-BV结合亲和力，表明生物物理相互作用系统适用于受体或细胞因子阻断和免疫细胞募集对癌症的抗癌ABS细胞。

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