A Supramolecular Strategy to Engineering a Non-photobleaching and Near-Infrared Absorbing Nano-J-Aggregate for Efficient Photothermal Therapy

Su, MH (Su, Meihui)^{[ 1,2,3 ]} ; Hang, QJ (Hang, Qiuju)^{[ 1,2 ]} ; Yan, XS (Yan, Xiaosa)^{[ 1,2,3 ]} ; Liu, YN (Liu, Yanan)^{[ 1,2,3 ]} ; Luo, P (Luo, Pei)^{[ 1,2,3 ]} ; Zhai, WH (Zhai, Wenhao)^{[ 1,2,3 ]} ; Zhang, QZ (Zhang, Qiangzhe)^{[ 1,2 ]} ; Li, LY (Li, Luyuan)^{[ 1,2 ]} ; Li, CH (Li, Changhua)^{[ 1,2,3 ]}

ACS NANO, 2021, 15(3): 5032-5042

DOI: 10.1021/acsnano.0c09993

摘要

The design of organic photothermal agents (PTAs) for in vivo applications face a demanding set of performance requirements, especially intense NIR-absorptivity and sufficient photobleaching resistance. J-aggregation offers a facile way to tune the optical properties of dyes, thus providing a general design platform for organic PTAs with the desired performance. Herein, we present a supramolecular strategy to build a water-stable, nonphotobleaching, and NIR-absorbing nano-PTA (J-NP) from J-aggregation of halogenated BODIPY dyes (BDP) for efficient in vivo photothermal therapy. Multiple intermolecular halogen-bonding and pi-pi stacking interactions triggered the formation of BDP J-aggregate, which adsorbed amphiphilic polymer chains on the surface to provide PEGylated sheetlike nano-J-aggregate (J-NS). We serendipitously discovered that the architecture of J-NS was remodeled during a long-time ultrafiltration process, generating a discrete spherical nano-J-aggregate (J-NP) with controlled size. Compared with J-NS, the remodeled J-NP significantly improved cellular uptake efficiency. J-aggregation brought J-NP striking photothermal performance, such as strong NIR-absorptivity, high photothermal conversion efficiency up to 72.0%, and favorable nonphotobleaching ability. PEGylation and shape-remodeling imparted by the polymer coating enabled J-NP to hold biocompatibility and stability in vivo, thereby exhibiting efficient antitumor photothermal activities. This work not only presents a facile J-aggregation strategy for preparing PTAs with high photothermal performance but also establishes a supramolecular platform that enables the appealing optical functions derived from J-aggregation to be applied in vivo.