Pengfei Rong

Biodegradable Gold Nanovesicles with an Ultrastrong Plasmonic Coupling Effect for Photoacoustic Imaging and Photothermal Therapy

The hierarchical assembly of gold nanoparticles (GNPs) allows the localized surface plasmon resonance peaks to be engineered to the near-infrared (NIR) region for enhanced photothermal therapy (PTT). Herein we report a novel theranostic platform based on biodegradable plasmonic gold nanovesicles for photoacoustic (PA) imaging and PTT. The disulfide bond at the terminus of a PEG-b-PCL block-copolymer graft enables dense packing of GNPs during the assembly process and induces ultrastrong plasmonic coupling between adjacent GNPs. The strong NIR absorption induced by plasmon coupling and very high photothermal conversion efficiency (η=37%) enable simultaneous thermal/PA imaging and enhanced PTT efficacy with improved clearance of the dissociated particles after the completion of PTT. The assembly of various nanocrystals with tailored optical, magnetic, and electronic properties into vesicle architectures opens new possibilities for the construction of multifunctional biodegradable platforms for biomedical applications.

Dye Loaded Ferritin Nanocages for Multimodal Imaging and Photothermal Therapy

Multimodal imaging-guided photothermal therapy (PTT), for the therapy of cancer, based on a ferritin (FRT) nanocage loaded with the near-infrared dye IR820 (designated DFRT) is demonstrated. The dual roles of DFRT (in imaging and PTT) are successfully balanced by using two different excitation wavelengths: 550 nm for high quantum-yield fluorescence imaging on the one hand and 808 nm for photoacoustic imaging and PTT with high photothermal conversion efficiency on the other.

Triphase Interface Synthesis of Plasmonic Gold Bellflowers as Near-Infrared Light Mediated Acoustic and Thermal Theranostics

We present a novel gold bellflower (GBF) platform with multiple-branched petals, prepared by a liquid–liquid–gas triphase interface system, for photoacoustic imaging (PAI)-guided photothermal therapy (PTT). Upon near-infrared (NIR) laser irradiation, the GBFs, with strong NIR absorption, showed very strong PA response and an ultrahigh photothermal conversion efficiency (η, ∼74%) among the reported photothermal conversion agents. The excellent performance in PAI and PTT is mainly attributed to the unique features of the GBFs: (i) multiple-branched petals with an enhanced local electromagnetic field, (ii) long narrow gaps between adjacent petals that induce a strong plasmonic coupling effect, and (iii) a bell-shaped nanostructure that can effectively amplify the acoustic signals during the acoustic propagation. Besides the notable PTT and an excellent PAI effect, the NIR-absorbing GBFs may also find applications in NIR light-triggered drug delivery, catalysis, surface enhanced Raman scattering, stealth, antireflection, IR sensors, telecommunications, and the like.

Photosensitizer Loaded Nano-Graphene for Multimodality Imaging Guided Tumor Photodynamic Therapy

Graphene, a 2-dimensional carbon nanomaterial, has attracted wide attention in biomedical applications, owing to its intrinsic physical and chemical properties. In this work, a photosensitizer molecule, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor®), is loaded onto polyethylene glycol (PEG)-functionalized graphene oxide (GO) via supramolecular π-π stacking. The obtained GO-PEG-HPPH complex shows high HPPH loading efficiency. The in vivo distribution and delivery were tracked by fluorescence imaging as well as positron emission tomography (PET) after radiolabeling of HPPH with 64Cu. Compared with free HPPH, GO-PEG-HPPH offers dramatically improved photodynamic cancer cell killing efficacy due to the increased tumor delivery of HPPH. Our study identifies a role for graphene as a carrier of PDT agents to improve PDT efficacy and increase long-term survival following treatment.

In Vivo Volumetric Photoacoustic Molecular Angiography and Therapeutic Monitoring with Targeted Plasmonic Nanostars

Photoacoustic (PA) imaging promises deeper tissue penetration while maintaining rich optical contrast as compared to other high resolution optical imaging techniques. In this report, a near-infrared pulse laser serves as the excitation source, and 128 ultrasonic transducers are spirally distributed on a hemispherical surface to receive PA signals for three-dimensional (3D) image reconstruction. With these attributes, the unique modality produces an isotropic and homogeneous spatial resolution (∼200 μm) with penetration depth of centimeters. Cyclic Arg-Gly-Asp (RGD) peptides conjugated plasmonic gold nanostars (RGD-GNS) are designed to specifically target over-expressed integrin α(v)β₃ on tumor neovasculature, enabling highly sensitive angiography and photothermal therapy (PTT). After the administration of RGD-GNS, tumor angiogenesis is clearly imaged with enhanced contrast, and the growth of tumor is effectively inhibited by PTT after laser irradiation. This study suggest that the PA angiography with plasmonic RGD-GNS can be applied as a triple functional platform for tumor diagnosis, PTT, and treatment monitoring. This PA technique offers deeper imaging depth with homogeneous resolution over existing optical imaging techniques for early diagnosis of tumor angiogenesis as well as on-the-spot nanotherapeutic evaluation.

Semimetal nanomaterials of antimony as highly efficient agent for photoacoustic imaging and photothermal therapy

In this study we report semimetal nanomaterials of antimony (Sb) as highly efficient agent for photoacoustic imaging (PAI) and photothermal therapy (PTT). The Sb nanorod bundles have been synthesized through a facile route by mixing 1-octadecane (ODE) and oleyl amine (OAm) as the solvent. The aqueous dispersion of PEGylated Sb NPs, due to its broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, is applicable as a photothermal agent driven by 808 nm laser with photothermal conversion efficiency up to 41%, noticeably higher than most of the PTT agents reported before. Our in vitro experiments also showed that cancer cell ablation effect of PEGylated Sb NPs was dependent on laser power. By intratumoral administration of PEGylated Sb NPs, 100% tumor ablation can be realized by using NIR laser irradiation with a lower power of 1 W/cm(2) for 5 min (or 0.5 W/cm(2) for 10 min) and no obvious toxic side effect is identified after photothermal treatment. Moreover, intense PA signal was also observed after intratumoral injection of PEGylated Sb NPs and NIR laser irradiation due to their strong NIR photoabsorption, suggesting PEGylated Sb NPs as a potential NIR PA agent. Based on the findings of this work, further development of using other semimetal nanocrystals as highly efficient NIR agents can be achieved for vivo tumor imaging and PTT.

VEGF-loaded graphene oxide as theranostics for multi-modality imaging-monitored targeting therapeutic angiogenesis of ischemic muscle

Herein we report the design and synthesis of multifunctional VEGF-loaded IR800-conjugated graphene oxide (GO-IR800-VEGF) for multi-modality imaging-monitored therapeutic angiogenesis of ischemic muscle. The as-prepared GO-IR800-VEGF positively targets VEGF receptors, maintains an elevated level of VEGF in ischemic tissues for a prolonged time, and finally leads to remarkable therapeutic angiogenesis of ischemic muscle. Although more efforts are required to further understand the in vivo behaviors and the long-term toxicology of GO, our work demonstrates the success of using GO for efficient VEGF delivery in vivo by intravenous administration and suggests the great promise of using graphene oxide in theranostic applications for treating ischemic disease.

A symmetrical fluorous dendron-cyanine dye-conjugated bimodal nanoprobe for quantitative 19F MRI and NIR fluorescence bioimaging.

(19)F MRI and optical imaging are two powerful noninvasive molecular imaging modalities in biomedical applications. (19)F MRI has great potential for high resolution in vivo imaging, while fluorescent probes enable ultracontrast cellular/tissue imaging with high accuracy and sensitivity. A bimodal nanoprobe is developed, integrating the merits of (19)F MRI and fluorescence imaging into a single synthetic molecule, which is further engineered into nanoprobe, by addressing shortcomings of conventional contrast agents to explore the quantitative (19)F MRI and fluorescence imaging and cell tracking. Results show that this bimodal imaging nanoprobe presents high correlation of (19)F MR signal and NIR fluorescence intensity in vitro and in vivo. Additionally, this nanoprobe enables quantitative (19)F MR analysis, confirmed by a complementary fluorescence analysis. This unique feature can hardly be obtained by traditional (19)F MRI contrast agents. It is envisioned that this nanoprobe can hold great potential for quantitative and sensitive multi-modal molecular imaging.

A cyclic HSV1-TK reporter for real-time PET imaging of apoptosis

Significance Apoptosis, or programmed cell death, is critical for maintaining tissue homeostasis and development in multicellular organisms. This article describes a unique molecularly engineered cyclic herpes simplex virus type 1–thymidine kinase (cTK) reporter for real-time apoptosis PET imaging. This reporter enables quantitative and real-time monitoring of caspase-3 activity in response to extracellular stimuli. As a PET reporter, cTK shows low background and high sensitivity in response to caspase-3 activation. The application of this particular caspase reporter system would be of significance in assisting preclinical high-throughput screening of different apoptosis-inducing drugs and monitoring their therapeutic efficacy in a noninvasive and quantitative manner. The coordination of cell proliferation and programmed death (apoptosis) is essential for normal physiology, and imbalance in these two opposing processes is implicated in various diseases. Objective and quantitative noninvasive imaging of apoptosis would significantly facilitate rapid screening as well as validation of therapeutic chemicals. Herein, we molecularly engineered an apoptosis switch-on PET-based cyclic herpes simplex virus type 1–thymidine kinase reporter (cTK266) containing a caspase-3 recognition domain as the switch. Translation of the reporter and protein splicing in healthy mammalian cells produce an inactive cyclic chimera. Upon apoptosis, caspase-3–specific cleavage of the circular product occurs, resulting in the restoration of the thymidine kinase activity, which can be detected in living cells and animals by noninvasive PET imaging. Our results showed the high sensitivity of this reporter in dynamic and quantitative imaging of apoptosis in living subjects. This reporter could be applied as a valuable tool for high-throughput functional screening of proapoptotic and antiapoptotic compounds in preclinical models in drug development, and monitoring the destination of therapeutic cells in clinical settings.

Dual-Modality Noninvasive Mapping of Sentinel Lymph Node by Photoacoustic and Near-Infrared Fluorescent Imaging Using Dye-Loaded Mesoporous Silica Nanoparticles.

The imaging of sentinel lymph nodes (SLNs), the first defense against primary tumor metastasis, has been considered as an important strategy for noninvasive tracking tumor metastasis in clinics. In this study, we developed an imaging contrast system based on fluorescent dye-loaded mesoporous silica nanoparticles (MSNPs) that integrate near-infrared (NIR) fluorescent and photoacoustic (PA) imaging modalities for efficient SLN mapping. By balancing the ratio of dye and nanoparticles for simultaneous optimization of dual-modality imaging (NIR and PA), the dye encapsulated MSNP platform was set up to generate both a moderate NIR emission and PA signals simultaneously. Moreover, the underlying mechanisms of the relevance between optical and PA properties were discovered. Subsequently, dual-modality imaging was achieved to visualize tumor draining SLNs up to 2 weeks in a 4T1 tumor metastatic model. Obvious differences in uptake rate and contrast between metastatic and normal SLNs were observed both in vivo and ex vivo. Based on all these imaging data, it was demonstrated that the dye-loaded MSNPs allow detection of regional lymph nodes in vivo with time-domain NIR fluorescent and PA imaging methods efficiently.