ABSTRACT
Pre-targeting of bispecific antibodies is probed to enhance tumour retention while limiting clearance of administered multifunctional branched PEGylated nanomedicines. The temporal influence of pre-targeting on polymer interaction with tumour cells and tissue is explored using in vitro assays through to preclinical validation.
Subject(s)
Antibodies, Bispecific , Nanostructures , Neoplasms , Humans , Nanomedicine , Neoplasms/drug therapy , PolymersABSTRACT
RNA interference (RNAi) therapy is an emerging class of biopharmaceutical that has immense potential in cancer medicine. RNAi medicines are based on synthetic oligonucleotides that can suppress a target protein in tumour cells with high specificity. This review explores the attractive prospect of using RNAi as a radiosensitiser by targeting the DNA damage response. There are a multitude of molecular targets involved in the detection and repair of DNA damage that are suitable for this purpose. Recent developments in delivery technologies such nanoparticle carriers and conjugation strategies have allowed RNAi therapeutics to enter clinical trials in the treatment of cancer. With further progress, RNAi targeting of the DNA damage response may hold great promise in guiding radiation oncology into the era of precision medicine.
Subject(s)
DNA Damage , Neoplasms/radiotherapy , RNA Interference , Radiation Tolerance/genetics , Drug Delivery Systems/methods , Gene Expression Regulation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Nanoparticles , Neoplasms/genetics , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/geneticsABSTRACT
We report a novel multifunctional hyperbranched polymer based on polyethylene glycol (PEG) as a nanomedicine platform that facilitates longitudinal and quantitative 89Zr-PET imaging, enhancing knowledge of nanomaterial biodistribution and pharmacokinetics/pharmacodynamics both in vivo and ex vivo. Anti-VEGF-A DNA aptamer functionalization increased tumour accumulation by >2-fold in a breast cancer model.
