Guanhui Gao

Graphene Quantum Dots Derived from Carbon Fibers

Graphene quantum dots (GQDs), which are edge-bound nanometer-size graphene pieces, have fascinating optical and electronic properties. These have been synthesized either by nanolithography or from starting materials such as graphene oxide (GO) by the chemical breakdown of their extended planar structure, both of which are multistep tedious processes. Here, we report that during the acid treatment and chemical exfoliation of traditional pitch-based carbon fibers, that are both cheap and commercially available, the stacked graphitic submicrometer domains of the fibers are easily broken down, leading to the creation of GQDs with different size distribution in scalable amounts. The as-produced GQDs, in the size range of 1-4 nm, show two-dimensional morphology, most of which present zigzag edge structure, and are 1-3 atomic layers thick. The photoluminescence of the GQDs can be tailored through varying the size of the GQDs by changing process parameters. Due to the luminescence stability, nanosecond lifetime, biocompatibility, low toxicity, and high water solubility, these GQDs are demonstrated to be excellent probes for high contrast bioimaging and biosensing applications.

Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a light-activated local treatment modality that is under intensive preclinical and clinical investigations for cancer. To enhance the treatment efficiency of phototherapy and reduce the light-associated side effects, it is highly desirable to improve drug accumulation and precision guided phototherapy for efficient conversion of the absorbed light energy to reactive oxygen species (ROS) and local hyperthermia. In the present study, a programmed assembly strategy was developed for the preparation of human serum albumin (HSA)-indocyanine green (ICG) nanoparticles (HSA-ICG NPs) by intermolecular disulfide conjugations. This study indicated that HSA-ICG NPs had a high accumulation with tumor-to-normal tissue ratio of 36.12±5.12 at 24 h and a long-term retention with more than 7 days in 4T1 tumor-bearing mice, where the tumor and its margin, normal tissue were clearly identified via ICG-based in vivo near-infrared (NIR) fluorescence and photoacoustic dual-modal imaging and spectrum-resolved technology. Meanwhile, HSA-ICG NPs efficiently induced ROS and local hyperthermia simultaneously for synergetic PDT/PTT treatments under a single NIR laser irradiation. After an intravenous injection of HSA-ICG NPs followed by imaging-guided precision phototherapy (808 nm, 0.8 W/cm2 for 5 min), the tumor was completely suppressed, no tumor recurrence and treatments-induced toxicity were observed. The results suggest that HSA-ICG NPs generated by programmed assembly as smart theranostic nanoplatforms are highly potential for imaging-guided cancer phototherapy with PDT/PTT synergistic effects.

Binary and ternary atomic layers built from carbon, boron, and nitrogen.

Two-dimensional (2D) atomic layers derived from bulk layered materials are very interesting from both scientific and application viewpoints, as evidenced from the story of graphene. Atomic layers of several such materials such as hexagonal boron nitride (h-BN) and dichalcogenides are examples that complement graphene. The observed unconventional properties of graphene has triggered interest in doping the hexagonal honeycomb lattice of graphene with atoms such as boron (B) and nitrogen (N) to obtain new layered structures. Individual atomic layers containing B, C, and N of various compositions conform to several stable phases in the three-component phase diagram of B-C-N. Additionally, stacking layers built from C and BN allows for the engineering of new van-der-Waals stacked materials with novel properties. In this paper, the synthesis, characterization, and properties of atomically thin layers, containing B, C, and N, as well as vertically assembled graphene/h-BN stacks are reviewed. The electrical, mechanical, and optical properties of graphene, h-BN, and their hybrid structure are also discussed along with the applications of such materials.

Improving drug accumulation and photothermal efficacy in tumor depending on size of ICG loaded lipid-polymer nanoparticles

A key challenge to strengthen anti-tumor efficacy is to improve drug accumulation in tumors through size control. To explore the biodistribution and tumor accumulation of nanoparticles, we developed indocyanine green (ICG) loaded poly (lactic-co-glycolic acid) (PLGA) -lecithin-polyethylene glycol (PEG) core-shell nanoparticles (INPs) with 39 nm, 68 nm and 116 nm via single-step nanoprecipitation. These INPs exhibited good monodispersity, excellent fluorescence and size stability, and enhanced temperature response after laser irradiation. Through cell uptake and photothermal efficiency in vitro, we demonstrated that 39 nm INPs were more easily be absorbed by pancreatic carcinoma tumor cells (BxPC-3) and showed better photothermal damage than that of 68 nm and 116 nm size of INPs. Simultaneously, the fluorescence of INPs offered a real-time imaging monitor for subcellular locating and in vivo metabolic distribution. Near-infrared imaging in vivo and photothermal therapy illustrated that 68 nm INPs showed the strongest efficiency to suppress tumor growth due to abundant accumulation in BxPC-3 xenograft tumor model. The findings revealed that a nontoxic, size-dependent, theranostic INPs model was built for in vivo cancer imaging and photothermal therapy without adverse effect.

NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

Dextran-based redox-responsive doxorubicin prodrug micelles for overcoming multidrug resistance

Multidrug resistance (MDR) is one of the critical reasons for the failure of cancer chemotherapy. To overcome MDR, we have developed redox-responsive doxorubicin prodrug (DEX-PEI(-SS-DOX)) micelles based on dextran-poly(ethylene imine) copolymers (DEX-PEI). The DEX-PEI(-SS-DOX) conjugates were conveniently prepared by grafting PEI to dextran, and then the anticancer drug doxorubicin (DOX) was conjugated to DEX-PEI through redox-responsive cleavable disulfide linkers. The amphiphilic DOX prodrug self-assembled into micelles in aqueous solution and the micelles showed an average size of 100–140 nm with a uniform spherical morphology. In vitro drug release studies showed that the prodrug micelles accomplished rapid drug release under reducing conditions. Confocal images revealed that the micelles enhance the cellular accumulation of DOX and achieve endosomal escape in human breast carcinoma multidrug resistant (MCF-7/ADR) cells. The therapeutic efficacy of the self-assembled DOX prodrug micelles against MCF-7/ADR cells in vitro was evaluated through the MTT assay. The results showed that the therapeutic efficacy of DOX prodrug micelles against MCF-7/ADR cells was remarkably enhanced compared with free DOX. These results indicate that the redox-responsive DOX prodrug micelles could be a promising delivery system for overcoming MDR.

Indocyanine Green-Loaded Polydopamine-Reduced Graphene Oxide Nanocomposites with Amplifying Photoacoustic and Photothermal Effects for Cancer Theranostics

Photoacoustic (PA) imaging and photothermal therapy (PTT) as light-induced theranostic platforms have been attracted much attention in recent years. However, the development of highly efficient and integrated phototheranostic nanoagents for amplifying PA imaging and PTT treatments poses great challenges. Here, we report a novel phototheranostic nanoagent using indocyanine green-loaded polydopamine-reduced graphene oxide nanocomposites (ICG-PDA-rGO) with amplifying PA and PTT effects for cancer theranostics. The results demonstrate that the PDA layer coating on the surface of rGO could effectively absorb a large number of ICG molecules, quench ICGs fluorescence, and enhance the PDA-rGOs optical absorption at 780 nm. The obtained ICG-PDA-rGO exhibits stronger PTT effect and higher PA contrast than that of pure GO and PDA-rGO. After PA imaging-guided PTT treatments, the tumors in 4T1 breast subcutaneous and orthotopic mice models are suppressed completely and no treatment-induced toxicity being observed. It illustrates that the ICG-PDA-rGO nanocomposites constitute a new class of theranostic nanomedicine for amplifying PA imaging and PTT treatments.

Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy.

Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.

Photosensitizer-conjugated redox-responsive dextran theranostic nanoparticles for near-infrared cancer imaging and photodynamic therapy

Photodynamic therapy (PDT) has emerged as an effective treatment for tumor with minimal nonspecific damage to adjacent healthy tissues. Herein, redox-responsive self-quenching polysaccharide-based theranostic nanoparticles (DEX-SS-Ce6 NPs) were developed for tumor imaging and photodynamic therapy. The dextran–chlorin e6 conjugates (DEX-SS-Ce6) could self-assemble into nanoparticles with uniform sphere shape in aqueous solution and exhibit cellular redox-responsive “OFF/ON” behavior of a fluorescence signal. In addition, the DEX-SS-Ce6 NPs demonstrated an effective cellular uptake property and high phototoxicity upon near-infrared (NIR) laser irradiation. More importantly, DEX-SS-Ce6 NP treated mice presented enhanced tumor targeting ability and improved photodynamic therapeutic efficiency in an in vivo study, compared with free Ce6 treated mice. These results suggest that the DEX-SS-Ce6 NP is a great potential system for tumor imaging and photodynamic therapy.

Indocyanine green–loaded polydopamine–iron ions coordination nanoparticles for photoacoustic/magnetic resonance dual-modal imaging-guided cancer photothermal therapy

Multi-modal imaging-guided cancer photothermal therapy (PTT) with advanced theranostic nanoagents can efficiently improve therapeutic efficacy and reduce treatment side effects. Herein, we have developed a theranostic nanoagent based on indocyanine green (ICG)-loaded polydopamine (PDA)-iron ions coordination nanoparticles (PDA-Fe3+-ICG NPs), which are used for photoacoustic (PA) and magnetic resonance (MR) dual-modal imaging-guided cancer PTT treatments. In this nanoplatform, ICG molecules, the U.S. Food and Drug Administration approved near-infrared (NIR) dye, absorbing on PDA NPs (a melanin-like biopolymer) to significantly increase the NIR optical absorption of PDA NPs nearly 6 times and decreases their fluorescence emission, which can improve the PA contrast ability and promote the photothermal conversion efficiency of PDA NPs. Meanwhile, Fe3+ ions chelated on the PDA NPs act as a T1-weighted MRI contrast agent (r1 = 14 mM-1 s-1). In a mouse 4T1 breast tumor model, PA/MRI dual-modal imaging and highly efficient PTT treatments with low laser density were achieved with remarkable therapeutic efficiency and minimal side effects. This study illustrates that the highly integrated and biocompatible PDA-based NPs can serve as a versatile nanoplatform by loading different imaging molecules and drugs for multi-modal imaging and cancer combination therapy.