Active-Targeted Dendritic Systems for Cancer Therapy – A SANS Study to Assess Nanoparticle Size and Distribution in Biorelevant Media

New chemotherapeutic drugs are increasingly making use of nanoscale architectures and active targeting approaches to minimise side effects while increasing efficacy. One such approach is the use of dendrimers, highly defined polymeric systems, which allow surface functionality to be tuned, with, for example targeting ligands, such as peptides. However systematic studies on the effect these ligands play on structure and binding are lacking. This work aims to use small angle neutron scattering (SANS) to explore how the number and size of the targeting ligands, and associated dendrimer-peptide linker, affect the size (Rg) and size distribution (PDI) of the peptide-dendrimer conjugated nanoparticles. Both of these effects will be assessed in two different biorelevant media, which simulate the conditions associated with both intravenous and oral dosage routes, to help direct future formulation decisions.

新型化疗药物正愈发多地采用纳米级结构与主动靶向策略，在提升治疗效力的同时最大限度降低副作用。其中一类策略是采用树状大分子（dendrimers）——一类结构明确的聚合物体系，该体系可对表面功能进行精准调控，例如引入肽类等靶向配体。然而目前仍缺乏针对此类配体对纳米结构与结合行为影响的系统性研究。本研究拟采用小角中子散射（small angle neutron scattering, SANS）技术，探究靶向配体的数量、尺寸以及与之相连的树状大分子-肽连接子，对肽-树状大分子偶联纳米颗粒的尺寸（回转半径Rg）与尺寸分布（多分散性指数PDI）的影响规律。本研究将在两种模拟静脉注射与口服给药途径生理环境的生物相关介质中，对上述两种影响进行评估，以期为后续的制剂配方开发提供指导。