Chimeric nanobody-decorated liposomes by self-assembly.
Md Mofizur RahmanJing WangGuosheng WangZhipeng SuYizeng LiYundi ChenJinguo MengYao YaoLefei WangStephan WilkensJifu TanJuntao LuoTao ZhangChuandong ZhuSung Hyun ChoLixue WangLuke P LeeYuan WanPublished in: Nature nanotechnology (2024)
Liposomes as drug vehicles have advantages, such as payload protection, tunable carrying capacity and improved biodistribution. However, due to the dysfunction of targeting moieties and payload loss during preparation, immunoliposomes have yet to be favoured in commercial manufacturing. Here we report a chemical modification-free biophysical approach for producing immunoliposomes in one step through the self-assembly of a chimeric nanobody (cNB) into liposome bilayers. cNB consists of a nanobody against human epidermal growth factor receptor 2 (HER2), a flexible peptide linker and a hydrophobic single transmembrane domain. We determined that 64% of therapeutic compounds can be encapsulated into 100-nm liposomes, and up to 2,500 cNBs can be anchored on liposomal membranes without steric hindrance under facile conditions. Subsequently, we demonstrate that drug-loaded immunoliposomes increase cytotoxicity on HER2-overexpressing cancer cell lines by 10- to 20-fold, inhibit the growth of xenograft tumours by 3.4-fold and improve survival by more than twofold.
Keyphrases
- drug delivery
- epidermal growth factor receptor
- cancer therapy
- cell therapy
- drug release
- tyrosine kinase
- advanced non small cell lung cancer
- endothelial cells
- reduced graphene oxide
- papillary thyroid
- quantum dots
- highly efficient
- adverse drug
- molecular dynamics simulations
- oxidative stress
- photodynamic therapy
- squamous cell
- induced pluripotent stem cells
- pluripotent stem cells
- stem cells
- squamous cell carcinoma
- emergency department
- molecularly imprinted
- ionic liquid
- young adults
- pet imaging
- positron emission tomography
- wound healing
- high resolution
- mass spectrometry