Signature Effects of Vector-Guided Systemic Nano Bioconjugate Delivery Across Blood-Brain Barrier of Normal, Alzheimer’s, and Tumor Mouse Models
Liron L. Israel, Anna Galstyan, Alysia Cox, Ekaterina S. Shatalova, Tao Sun, Mohammad-Harun Rashid, Zachary B. Grodzinski, Antonella Chiechi, Dieu‐Trang Fuchs, Rameshwar Patil, Maya Koronyo‐Hamaoui, Keith L. Black, Julia Y. Ljubimova, Eggehard Holler
Abstract
brain delivery signatures of the nanoconjugates were recapitulated in mouse brains of normal, tumor (glioblastoma), and Alzheimer's disease (AD) models. BBB permeation of the tumor was most efficient, followed by normal and then AD-like brain. In tumor-bearing and normal brains, AP2 was the top performing vector; however, in AD models, D3 and D1 peptides were superior ones. The TfR vector B6 was equally efficient in normal and AD-model brains. Cross-permeation efficacies are manifested through modulated vector coligation and dosage escalation such as supra-linear dose dependence and crossover transcytosis activities.