NIR‐II Perylene Monoimide‐Based Photothermal Agent with Strengthened Donor–Acceptor Conjugation for Deep Orthotopic Glioblastoma Phototheranostics

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 19; no. 19; pp. e2300203 - n/a
• Main Authors: Guan, Jun, Liu, Chang, Ji, Chendong, Zhang, Wenchao, Fan, Zongyang, He, Penggang, Ouyang, Qiuhong, Qin, Meng, Yin, Meizhen
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.05.2023
• Subjects: Blood-Brain Barrier - pathology; Brain; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - therapy; Charge transfer; Choline; Conjugation; Copolymers; crossing blood‐brain barriers; deep glioblastoma; Encapsulation; Glioblastoma - diagnostic imaging; Glioblastoma - pathology; Glioblastoma - therapy; Humans; Methacryloyloxyethyl phosphorylcholine; Nanoparticles; Nanotechnology; Near infrared radiation; near infrared‐II; Organic chemistry; Perylene; perylenes; Phototherapy - methods; photothermal therapies; Receptors; Theranostic Nanomedicine - methods; crossing blood-brain barriers; near infrared-II; photothermal therapies; deep glioblastoma; perylenes
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202300203

Extensive efforts have been devoted to the design of organic photothermal agents (PTAs) that absorb in the second near‐infrared (NIR‐II) bio‐window, which can provide deeper tissue penetration that is significant for phototheranostics of lethal brain tumors. Herein, the first example of NIR‐II‐absorbing small organic molecule (N1) derived from perylene monoamide (PMI) and its bio‐application after nano‐encapsulation of N1 to function as a nano‐agent for phototheranostics of deep orthotopic glioblastoma (GBM) is reported. By adopting a dual modification strategy of introducing a donor‐acceptor unit and extending π‐conjugation, the obtained N1 can absorb in 1000–1400 nm region and exhibit high photothermal conversation due to the apparent intramolecular charge transfer (ICT). A choline analogue, 2‐methacryloyloxyethyl phosphorylcholine, capable of interacting specifically with receptors on the surface of the blood‐brain barrier (BBB), is used to fabricate the amphiphilic copolymer for the nano‐encapsulation of N1. The obtained nanoparticles demonstrate efficient BBB‐crossing due to the receptor‐mediated transcytosis as well as the small nanoparticle size of approximately 26 nm. The prepared nanoparticles exhibit excellent photoacoustic imaging and significant growth inhibition of deep orthotopic GBM. The current study demonstrates the enormous potential of PMI‐based NIR‐II PTAs and provides an efficient phototheranostic paradigm for deep orthotopic GBM. A NIR‐II‐absorbing perylene‐monoimide‐based photothermal agent (N1) has been developed for the first time by D‐A units modification and π‐conjugation extension. N1 is further encapsulated by ligand‐possessing amphiphilic copolymers to obtain blood‐brainbarrier‐crossing nanoparticles (N1@2P NPs) with an optimal size of ≈26 nm. N1@2P NPs exhibit enhanced enrichment, high‐resolution real‐time PA imaging, and photothermal ablation in deep orthotopic glioblastoma.