Advancements in the Blood-Brain Barrier Penetrating Nanoplatforms for Brain Related Disease Diagnostics and Therapeutic Applications

Abstract

Noninvasive treatments to treat the brain-related disorders have been paying more significant attention and it is an emerging topic. However, overcoming the blood brain barrier (BBB) is a key obstacle to most of the therapeutic drugs to enter into the brain tissue, which significantly results in lower accumulation of therapeutic drugs in the brain. Thus, administering the large quantity/doses of drugs raises more concerns of adverse side effects. Nanoparticle (NP)-mediated drug delivery systems are seen as potential means of enhancing drug transport across the BBB and to targeted brain tissue. These systems offer more accumulation of therapeutic drugs at the tumor site and prolong circulation time in the blood. In this review, we summarize the current knowledge and advancements on various nanoplatforms (NF) and discusses the use of nanoparticles for successful cross of BBB to treat the brain-related disorders such as brain tumors, Alzheimer's disease, Parkinson's disease, and stroke.

Keywords: Alzheimer’s disease; Parkinson’s disease; blood brain barrier; brain tumor; nanoparticle; stroke.

Figure 1

Structure of the blood brain barrier (BBB) and transport pathways across the BBB. Reproduced with permission from Reference [14].

Figure 2

Schematic illustration of the blood brain barrier (BBB)-penetrating nanoplatforms (NFs) for targeted delivery and therapeutics into the brain tissue to treat brain-related disorders.

Figure 3

In vivo anti-tumor activity of G23-Dox/alg-Fe₃O₄ NPs. (A) Schematic representation of synthesis process and BBB penetrating Dox delivery. (B) In vivo MRI contrast imaging abilities of alg-Fe₃O₄ NPs and G23-alg-Fe₃O₄ NPs. (C) In vivo luminescence images show from U87MG-luc2 cells monitored using the IVIS imaging system after mice were intravenously injected with G23-Dox/alg-Fe₃O₄ NPs for seven days. (D) Body weights of mice during the treatment. Reproduced with permission from Reference [69].

Figure 4

Cell membranes coated on ICG loaded nanoparticle (PCL-ICG) nanoparticles (NPs). (A) Representative bioluminescence images of U87MG-Luc glioma-bearing mice in different groups: (1) phosphate buffered saline (PBS), (2) normal cell coated ICG loaded nanoparticle (COS7-PCL-ICG), (3) COS7-PCL-ICG + laser, (4) B16-PCL-ICG, and (5) B16-PCL-ICG + laser under 808-nm laser irradiation (1 W cm⁻², 5 min). CICG = 1 mg kg⁻¹. (B) Quantitative fluorescence signal intensity in the brain. Reproduced with permission from Reference [74].

Figure 5

Focused ultrasound-induced blood–brain barrier opening strategy. (A) Schematic representation of size-dependent nanoparticle (NP) delivery to the brain via a focused ultrasound (FUS). (B) TEM images of 3, 15, 120-nm sized Au NPs. (C) Distribution of Au NPs in mouse brains in vivo models. (D) Kinetic modeling studies of FUS-assisted NPs delivery into the brain. Reproduced with permission from Reference [104].

Figure 6

Zwitterionic poly(carboxybetaine) (PCB)-based nanoparticle (MCPZFS NPs) for treating Alzheimer’s disease (AD). (A) Schematic illustration of the MCPZFS NPs for AD. (B) Characterization of the NPs. (C) Effect of NPs on the inflammatory regulation of microglia and (D) the effect of NPs on phagocytosis and degradation of Aβ by microglia. Data are presented as the mean ± SD. * p < 0.05, ** p < 0.01, *** p < 0.001. Reproduced with permission from Reference [117].

Figure 7

Dual-target traceable nanodrug for Parkinson’s disease (PD) treatment. (A) Schematic representation of synthesis of nanodrug and application for PD. (B) Systematic characterization of dual-target traceable nanodrug (B6ME-NPs). (C) Confocal microscopy (CSLM) and flow cytometry uptake studies to confirm the successful blood brain barrier (BBB) crossing. (D) Fluorescence and magnetic resonance (MR) images of the mice model after 24 h of i.v. injection of the nanodrug. Data are presented as the mean ± SD. * p < 0.05, ** p < 0.01, *** p < 0.001. Reproduced with permission from Reference [124].

Figure 8

Schematic representation of magnetosome-like ferrimagnetic iron oxide nanochains (MFION)-based fabrication of Mesenchymal stem cells (MSCs) for the recovery of post-ischemic stroke. Reproduced with permission from Reference [151].