O-Nitrobenzyl-alt-(phenylethynyl)benzene copolymer-based nanoaggregates with highly efficient two-photon-triggered degradable properties via a FRET process

Light-controlled drug delivery systems constituted an appealing means to realize drug release spatiotemporally at the site of interest with high specificity. However, the utilization of light-activatable systems was hindered by the lack of suitable drug carriers that respond to near infrared light. Here, we reported a two-photon-triggered degradable amphiphilic copolymer in which the photo-cleavable species o-nitrobenzyl (ONB) was positioned alternately into the backbone of a (phenylethynyl)benzene (PEB) based polymer. Further, hydrophilic polyethylene glycol was grafted onto the side chain of the copolymer to obtain an amphiphilic structure, which could self-assemble into nanoaggregates (NAs). The state of NAs was unambiguously demonstrated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In this structure, the PEB fluorophore with a relatively good two-photon absorption (TPA) cross-section performed fluorescence resonance energy transfer (FRET) to ONB under 800 nm irradiation for two-photon-triggered photolysis. The aggregation state of copolymer NAs provided a large TPA cross-section and effective intermolecular/intramolecular FRET between PEB and ONB, which was beneficial for improving the degradation efficiency. As a proof of concept, a hydrophobic drug (Nile Red) was encapsulated into the NAs via a self-assembly method and was successfully released due to the photo-destruction of copolymer NAs upon two-photon excitation, thereby providing a variety of potential applications in two-photon-responsive drug delivery.