Through Scalp and Skull NIR‐II Photothermal Therapy of Deep Orthotopic Brain Tumors with Precise Photoacoustic Imaging Guidance

Abstract

Brain tumor is one of the most lethal cancers owing to the existence of blood-brain barrier and blood-brain tumor barrier as well as the lack of highly effective brain tumor treatment paradigms. Herein, cyclo(Arg-Gly-Asp-D-Phe-Lys(mpa)) decorated biocompatible and photostable conjugated polymer nanoparticles with strong absorption in the second near-infrared (NIR-II) window are developed for precise photoacoustic imaging and spatiotemporal photothermal therapy of brain tumor through scalp and skull. Evidenced by the higher efficiency to penetrate scalp and skull for 1064 nm laser as compared to common 808 nm laser, NIR-II brain-tumor photothermal therapy is highly effective. In addition, via a real-time photoacoustic imaging system, the nanoparticles assist clear pinpointing of glioma at a depth of almost 3 mm through scalp and skull with an ultrahigh signal-to-background ratio of 90. After spatiotemporal photothermal treatment, the tumor progression is effectively inhibited and the survival spans of mice are significantly extended. This study demonstrates that NIR-II conjugated polymer nanoparticles are promising for precise imaging and treatment of brain tumors.

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

“…[ 1 ] Despite the tremendous efforts made in the past few years, treatments and diagnoses of GBM remain limited due to the existence of the blood–brain barrier (BBB). [ 2 ] BBB is mainly composed of brain endothelial cells, highly specialized basal membrane, pericytes embedded in the basal membrane, and astrocytic end feet. [ 3 ] The tight junction of complexes between adjacent endothelial cells further strengthens the functional integrity of BBB, which strictly monitors and controls the import and export of different substances of the brain.…”

“…RMT is the most commonly adopted strategy, which involves the binding of target ligands conjugated onto the nanoparticle to corresponding receptors expressed on the surface of brain endothelial cells to improve the delivery of loaded therapeutic agents into the brain. [ 2,11–13 ] Recently, several target ligands including transferrin, lactoferrin, and angiopep‐2 have been exploited to cross BBB by receptor‐mediated transcytosis. [ 12,14–16 ] However, the less than 1.0% of the brain accumulation rate of these nanoparticles cannot meet the requirements of clinical use, which is due to the low efficiency of ligand upload on nanoparticles, weak binding ability with receptors, and the competition of high concentration of endogenous ligands in the blood.…”

Second Near‐Infrared Absorbing Agents for Photoacoustic Imaging and Photothermal Therapy

“…b) Hematoxylin and Eosin (H&E) staining results of brain slices after PTT treatment on day 19. c) Mice survival rate after photothermal treatment. Reproduced with permission . Copyright 2018, WILEY‐VCH Verlag GmbH & Co. KGaA.…”

“…SPs with donor–acceptor (D–A) structure were translated into NPs and applied for PA imaging–guided NIR‐II PTT, including P8 (D: ((4,8‐bis((2‐octyldodecyl)oxy)‐benzo[1,2‐ b :4,5‐ b′ ]dithiophene‐2,6 diyl)bis(trimethylstannane))), A: (4,8‐bis(5‐bromo‐4‐(2‐ethylhexyl)thiophen‐2‐yl)benzo[1,2‐ c :4,5‐ c′ ]bis[1,2,5]thiadiazole)), P9 (D: bithiophene, A: bis(5‐oxothieno[3,2‐ b ]pyrrole‐6‐ylidene)benzodifurandione), and P10 (D: 2,2‐bithiophene, A: thiophene‐fused benzodifurandione‐based oligo( p ‐phenylenevinylene)) (Figure ). Mass extinction coefficients at 1064 nm of these corresponding SPNs followed the order: SPN9 (83.9 L g −1 cm −1 ) > SPN10 (39.5 L g −1 cm −1 ) > SPN8 (22.6 L g −1 cm −1 ).…”

Organic/polymer photothermal nanoagents for photoacoustic imaging and photothermal therapy in vivo

“…Moreover, since photons need to penetrate tissues to supply energy to photothermal agents during in vivo application, extending the absorption wavelength with stronger tissue penetration ability is also an effective way to enhance the PA imaging and PTT effect of photothermal agents. Recently, Liu and co-workers [69] developed a kind of SPNs with strong absorption in the second near-infrared (NIR-II) window for enhanced PA imaging and PTT of brain tumor. By alternatively polymerization of an electron-rich donor and an electrondeficient acceptor, a planar donor-acceptor structured SP (P1) with a broad NIR-II absorption peak near 1064 nm was constructed ( Fig.…”