Yufu Tang

Engineering Lysosome-Targeting BODIPY Nanoparticles for Photoacoustic Imaging and Photodynamic Therapy under Near-Infrared Light

Developing lysosome-targeting organic nanoparticles combined with photoacoustic imaging (PAI) and photodynamic therapy (PDT) functions toward personalized medicine are highly desired yet challenging. Here, for the first time, lysosome-targeting BODIPY nanoparticles were engineered by encapsulating near-infrared (NIR) absorbed BODIPY dye within amphiphilic DSPE-mPEG5000 for high-performing lysosomal PAI and acid-activatable PDT against cancer cells under NIR light.

Amphiphilic Semiconducting Oligomer for Near-Infrared Photoacoustic and Fluorescence Imaging

Semiconducting polymer nanoparticles (SPNs) have emerged as an alternative class of optical nanoagents for imaging applications. However, the general preparation method of SPNs is nanoprecipitation, which is likely to encounter the issue of nanoparticle dissociation. We herein report nondissociable near-infrared (NIR)-absorbing organic semiconducting nanoparticles for in vivo photoacoustic (PA) and fluorescence imaging. The nanoparticles are self-assembled from an amphiphilic semiconducting oligomer (ASO) that has a hydrophobic semiconducting oligomer backbone attached by hydrophilic poly(ethylene glycol) (PEG) side chains. The ASO has a higher structural stability and brighter PA signals compared to those of its counterpart nanoparticles synthesized by nanoprecipitation. The small size and the PEG-passivated surface of the ASO allow it to passively target to and efficiently accumulate in the tumor of living mice, permitting tumor imaging with high signal-to-background ratios. Our study provides new NIR-absorbing organic nanoparticles for PA and fluorescence imaging, which also have the potential to be used as a drug carrier for theranostics.

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.

Perylene Diimide-Grafted Polymeric Nanoparticles Chelated with Gd3+ for Photoacoustic/T1-Weighted Magnetic Resonance Imaging-Guided Photothermal Therapy

Developing versatile and easily prepared nanomaterials with both imaging and therapeutic properties have received significant attention in cancer diagnostics and therapeutics. Here, we facilely fabricated Gd3+-chelated poly(isobutylene-alt-maleic anhydride) (PMA) framework pendent with perylene-3,4,9,10-tetracarboxylic diimide (PDI) derivatives and poly(ethylene glycol) (PEG) as an efficient theranostic platform for dual-modal photoacoustic imaging (PAI) and magnetic resonance imaging (MRI)-guided photothermal therapy. The obtained polymeric nanoparticles (NPs) chelated with Gd3+ (PMA-PDI-PEG-Gd NPs) exhibited a high T1 relaxivity coefficient (13.95 mM-1 s-1) even at the higher magnetic fields. After 3.5 h of tail vein injection of PMA-PDI-PEG-Gd NPs, the tumor areas showed conspicuous enhancement in both photoacoustic signal and T1-weighted MRI intensity, indicating the efficient accumulation of PMA-PDI-PEG-Gd NPs owing to the enhanced permeation and retention effect. In addition, the excellent tumor ablation therapeutic effect in vivo was demonstrated with living mice. Overall, our work illustrated a straightforward synthetic strategy for engineering multifunctional polymeric nanoparticles for dual-modal imaging to obtain more accurate information for efficient diagnosis and therapy.

A Single Composition Architecture-Based Nanoprobe for Ratiometric Photoacoustic Imaging of Glutathione (GSH) in Living Mice

As one of the reduction species, glutathione (GSH) plays a tremendous role in regulating the homeostasis of redox state in living body. Accurate imaging of GSH in vivo is highly desired to provide a real-time visualization of physiological and pathological conditions while it is still a big challenge. Recently developed photoacoustic imaging (PAI) with high resolution and deep penetration characteristics is more promising for in vivo GSH detection. However, its application is dramatically limited by the difficult designation of photoacoustic probes with changeable near-infrared (NIR)-absorption under reductive activation. A cyanine derivative-based activatable probe is developed for in vivo ratiometric PAI of GSH for the first time. The probe is structurally designed to output ratiometric signals toward GSH in NIR-absorption region based on the cleavage of disulfide bond followed by a subsequent exchange between the secondary amine and sulfydryl group formed. Such a ratiometric manner provides high signal-to-noise imaging of blood vessels and their surrounding areas in tumor. Concomitantly, it also exhibits good specificity toward GSH over other thiols. Furthermore, the single composition architecture of the probe effectively overcomes the leakage issue compared with traditional multicomposition architecture-based nanoprobe, thus enhancing the imaging accuracy and fidelity in living body.

Activatable Semiconducting Theranostics: Simultaneous Generation and Ratiometric Photoacoustic Imaging of Reactive Oxygen Species In Vivo

Enhancing the generation of reactive oxygen species (ROS) is an effective anticancer strategy. However, it is a great challenge to control the production and to image ROS in vivo, both of which are vital for improving the efficacy and accuracy of cancer therapy. Herein, an activatable semiconducting theranostic nanoparticle (NP) platform is developed that can simultaneously enhance ROS generation while self-monitoring its levels through ratiometric photoacoustic (PA) imaging. The NP platform can further guide in vivo therapeutic effect in tumors. The theranostic NP platform is composed of: (i) cisplatin prodrug and ferric ion catalyst for ROS generation, a part of combination cancer therapy; and (ii) a ratiometric PA imaging nanoprobe consisting of inert semiconducting perylene-diimide (PDI) and ROS activatable near-infrared dye (IR790s), used in ratiometric PA imaging of ROS during cancer treatment. Ratiometric PA signals are measured at two near-infrared excitation wavelengths: 680 and 790 nm for PDI and IR790s, respectively. The measurements show highly accurate visualization of • OH generation in vivo. This novel ROS responsive organic theranostic NP allows not only synergistic cancer chemotherapy but also real-time monitoring of the therapeutic effect through ratiometric PA imaging.