Cancer Cell Membrane-Biomimetic Nanoparticles for Homologous-Targeting Dual-Modal Imaging and Photothermal Therapy.

An active cell membrane-camouflaged nanoparticle, owning to membrane antigens and membrane structure, can achieve special properties such as specific recognition, long blood circulation, and immune escaping. Herein, we reported a cancer cell membrane-cloaked nanoparticle system as a theranostic nanoplatform. The biomimetic nanoparticles (indocyanine green (ICG)-loaded and cancer cell membrane-coated nanoparticles, ICNPs) exhibit a core-shell nanostructure consisting of an ICG-polymeric core and cancer cell membrane shell. ICNPs demonstrated specific homologous targeting to cancer cells with good monodispersity, preferable photothermal response, and excellent fluorescence/photoacoustic (FL/PA) imaging properties. Benefited from the functionalization of the homologous binding adhesion molecules from cancer cell membranes, ICNPs significantly promoted cell endocytosis and homologous-targeting tumor accumulation in vivo. Moreover, ICNPs were also good at disguising as cells to decrease interception by the liver and kidney. Through near-infrared (NIR)-FL/PA dual-modal imaging, ICNPs could realize real-time monitored in vivo dynamic distribution with high spatial resolution and deep penetration. Under NIR laser irradiation, ICNPs exhibited highly efficient photothermal therapy to eradicate xenografted tumor. The robust ICNPs with homologous properties of cancer cell membranes can serve as a bionic nanoplatform for cancer-targeted imaging and phototherapy.

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.

Smart hyaluronidase-actived theranostic micelles for dual-modal imaging guided photodynamic therapy.

We here report smart hyaluronidase-actived theranostic nanoparticles based on hyaluronic acid (HA) coupled with chlorin e6 (Ce6) via adipic dihydrazide (ADH) forming HA-ADH-Ce6 conjugates and self-assembling into HACE NPs. The resulting nanoparticles showed stable nano-structure in aqueous condition with uniform size distribution and can be actively disassembled in the presence of hyaluronidase (over-expressed in tumor cells), exhibiting hyaluronidase-responsive "OFF/ON" behavior of fluorescence signal. The HACE NPs were rapidly taken up to human lung cancer cells A549 via CD44 (the HA receptor on the surface of tumor cells) receptor mediated endocytosis. Upon laser irradiation, the HACE NPs realized good near-infrared fluorescence imaging and photoacoustic imaging in the tumor bearing mice, which showed 5-fold higher fluorescence intensity and 3-fold higher photoacoustic (PA) intensity than free Ce6, respectively. In addition, under low dose of laser power, the HACE NPs presented more effective photodynamic therapy to suppression of tumor growth than free Ce6 in vitro and in vivo. Overall, these results suggest that the well-defined HACE NPs is a biocompatible theranostic nanoplatform for in vivo dual-modal tumor imaging and phototherapy simultaneously.

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 ICG's fluorescence, and enhance the PDA-rGO's 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.

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.

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.

Dextran based sensitive theranostic nanoparticles for near-infrared imaging and photothermal therapy in vitro.

Indocyanine green (ICG) nanoparticles were developed via electrostatic interactions of ICG and dextran based block copolymers (PEG-dextran(-SS-NH2)) as near-infrared (NIR) theranostic nanoparticles. The nanoparticles could be activated from "OFF" to "ON" of NIR fluorescence in an intracellular environment and used for NIR imaging and photothermal therapy.

Protein-assisted fabrication of nano-reduced graphene oxide for combined in vivo photoacoustic imaging and photothermal therapy.

Theranostic agents are attracting a great deal of attention in personalized medicine. Here, we developed a protein-based, facile method for fabrication of nanosized, reduced graphene oxide (nano-rGO) with high stability and low cytotoxicity. We constructed highly integrated photoacoustic/ultrasonic dual-modality imaging and photothermal therapy platforms, and further demonstrated that the prepared nano-rGO can be used as ready-to-use theranostic agents for both photoacoustic imaging and photothermal therapy without further surface modification. Intravenous administration of nano-rGO in tumor-bearing mice showed rapid and significant photoacoustic signal enhancement in the tumor region, indicating its excellence for passive targeting and photoacoustic imaging. Meanwhile, using a continuous-wave near-infrared laser, cancer cells in vivo were efficiently ablated, due to the photothermal effect of nano-rGO. The results suggest that the nano-rGO with protein-assisted fabrication was well suited for photoacoustic imaging and photothermal therapy of tumor, which is promising for theranostic nanomedicine.

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.