A Biocompatible Second Near-Infrared Nanozyme for Spatiotemporal and Non-Invasive Attenuation of Amyloid Deposition through Scalp and Skull

Abstract

Phototherapy, such as photodynamic therapy and photothermal therapy, holds great potential for modulation of Alzheimer’s β-amyloid (Aβ) self-assembly. Unfortunately, current works for phototherapy of Alzheimer’s disease (AD) are just employing either visible or first near-infrared (NIR-I) light with limited tissue penetration, which can not avoid damaging nearby normal tissues of AD patients through the dense skull and scalp. To overcome the shortcomings of AD phototherapy, herein we report an amyloid targeting, N-doped three-dimensional mesoporous carbon nanosphere (KD8@N-MCNs) as a second near-infrared (NIR-II) PTT agent. This makes it possible for photothermal dissociation of Aβ aggregates through the scalp and skull in a NIR-II window without hurting nearby normal tissues. Besides, KD8@N-MCNs have both superoxide dismutase and catalase activities, which can scavenge intracellular superfluous reactive oxygen species and alleviate neuroinflammation in vivo. Furthermore, KD8@N-MCNs efficiently cross the blood–brain barrier owing to the covalently grafted target peptides of KLVFFAED on the nanosphere surface. In vivo studies demonstrate that KD8@N-MCNs decrease Aβ deposits, ameliorate memory deficits, and alleviate neuroinflammation in the 3xTg-AD mouse model. Our work provides a biocompatible and non-invasive way to attenuate AD-associated pathology.

Self-assembled organic nanomedicine enables ultrastable photo-to-heat converting theranostics in the second near-infrared biowindow

“…For instance, after the penetration through 2 mm of chicken breast tissue, the residue power density for 1064 nm and 808 nm lasers was determined to be 0.9 W cm −2 and 0.6 W cm −2 under the same original power density, respectively. This difference was contributed to better transmittance capability and higher MPE of 1064 nm laser in comparison with that of 808 nm laser [45][46][47] . To further verify higher deep-tissue photothermal heating performance of NIR-II laser, Nano-BFF solution was irradiated by 1064 nm or 808 nm laser under varied tissue thicknesses (Fig.…”

Biomimetic Dendrimer–Peptide Conjugates for Early Multi‐Target Therapy of Alzheimer's Disease by Inflammatory Microenvironment Modulation

“…Ab peptide (KLVFFAED) has been reported as a binding peptide with RAGE derived from Aβ, which is nontoxic and an ideal agent for brain targeting. [ 27 ] The stability of the Ab peptide in the ROS environment was first verified with MOLDI‐TOF, which demonstrated the targeting stability of APBP in the AD microenvironment (Figure S20, Supporting Information). To evaluate the efficiency of nanoconjugate targeting, SH‐SY5Y cells, BV2 cells, and brain capillary endothelial cells (BCECs) were used as in vitro models for neurons, microglia, and the BBB, as they were all reported to express RAGE (Figures S21 and S24, Supporting Information).…”

Nanomaterials for Modulating the Aggregation of β-Amyloid Peptides

“…Thus, utilizing excitation light at second near-infrared light (NIR-II, 1000–1700 nm) is a more attractive option for deeper tissue penetration and a lower signal-to-noise ratio. Ma et al designed Aβ targeting, N-doped three-dimensional mesoporous carbon nanospheres (KD8@N-MCNs) for NIR-II PTT of AD ( Figure 5 A) [ 82 ]. KLVFFAED (KD8) was used as the target of Aβ and receptor of the advanced glycation end-products (AGEs).…”