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The fabrication of functional nanoparticles with unique ultra-sensitivity to endogenous tumor microenvironment (TME) is of great significance for their improved theranostic performance and easy excretion out of the body, which has not been realized among diverse nano-sized photothermal agents for photothermal therapy (PTT) of tumor. In this work, we report on the synthesis of 2D ultrathin MnO 2 nanosheets for highly efficient PTT against tumor with ultra-sensitivity to endogenous TME. These ultrathin 2D MnO 2 nanosheets show the intriguing characteristic of disintegration and releasing of Mn 2+ in response to the mild acidic condition and elevated reducing microenvironment of TME, which has successfully realized the pH- and reducing-responsive T 1 -weighted magnetic resonance imaging of tumor. Importantly, the high PTT efficiency of 2D MnO 2 nanosheets responsive to exogenous NIR irradiation has been systematically demonstrated both in vitro and in vivo for suppressing the tumor growth. This first report on the exploring of TME-sensitive photothermal agents with concurrent diagnostic and therapeutic (theranostic) functions significantly broadens the biomedical application of 2D functional biomaterials, which also promotes the further potential clinical translations of nano-sized photothermal agents. [ABSTRACT FROM AUTHOR]

The combination of chemotherapy with photothermal therapy, which may lead to improved therapeutic efficacies and reduced side effects of conventional chemotherapy, would require safe drug delivery systems (DDSs) with strong near-infrared (NIR) absorbance, efficient drug loading, and effective tumor homing ability. Herein, we fabricate nano-assemblies containing J-aggregates of a NIR dye, IR825, for drug delivery and combined photothermal & chemotherapy of cancer. It is found that IR825 could be complexed with a low-molecular-weight cationic polymer polyethylenimine (PEI), forming IR825@PEI J-aggregates with greatly enhanced NIR absorbance red-shifted to 915 nm. Those nano-assemblies of J-aggregates are further modified with polyethylene glycol (PEG), obtaining IR825@PEI-PEG nano-complex which exhibits great dispersity in physiological solutions, excellent photostability, and is able to efficiently load chemotherapeutic drug doxorubicin (DOX) via a unique strategy different from drug loading in conventional amphiphilic polymer-based DDSs. In vivo animal experiments uncover that IR825@PEI-PEG/DOX upon intravenous injection into tumor-bearing mice shows rather high tumor uptake as illustrated by photoacoustic imaging. In vivo combined photothermal & chemotherapy is then carried out, demonstrating great synergistic anti-tumor therapeutic effect remarkably superior to those achieved by the respective mono-therapies. Hence, we present a novel type of nanoscale DDSs based on nano-assemblies of small molecules without involving amphiphilic polymers, promising for imaging-guided combination cancer therapy. [ABSTRACT FROM AUTHOR]

Theranostic agents with both imaging and therapeutic functions have attracted enormous interests in cancer diagnosis and treatment in recent years. In this work, we develop a novel theranostic agent based on Prussian blue nanocubes (PB NCs), a clinically approved agent with strong near-infrared (NIR) absorbance and intrinsic paramagnetic property, for in vivo bimodal imaging-guided photothermal therapy. After being coated with polyethylene glycol (PEG), the obtained PB-PEG NCs are highly stable in various physiological solutions. In vivo T 1 -weighted magnetic resonance (MR) and photoacoustic tomography (PAT) bimodal imaging uncover that PB-PEG NCs after intravenous (i.v.) injection show high uptake in the tumor. Utilizing the strong and super stable NIR absorbance of PB, in vivo cancer treatment is then conducted upon i.v. injection of PB-PEG NCs followed by NIR laser irradiation of the tumors, achieving excellent therapeutic efficacy in a mouse tumor model. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of PB-PEG NCs to mice at our tested dose, which is two-fold of the imaging/therapy dose, within two months. Our work highlights the great promise of Prussian blue with well engineered surface coating as a multifunctional nanoprobe for imaging-guided cancer therapy. [ABSTRACT FROM AUTHOR]

A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a ‘photothermal ablation assisted surgery’ strategy, promising for future clinical cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract: The ‘sea urchin’-like nanostructures with particular small size (<100 nm) and abundant multi-tips have not yet been employed for the cancer photothermal therapy (PTT). Here we report sub-100 nm hollow Au–Ag alloy nanourchins (HAAA-NUs) with ultrahigh density of nanotips synthesized via a facile seed-mediated growth. The HAAA-NUs exhibit a remarkably integrated high-quality photothermal feature including well-defined but tunable surface plasmon resonance peak, strong absorption (2.2 × 1010 M−1 cm−1) as well as high photothermal conversion efficiency (80.4%) in the near-infrared region. Importantly, the HAAA-NUs demonstrate improved photothermal stability verified via continuous exposition and cyclic irradiation of laser beam. The cell assay, in vitro cell ablation and in vivo breast cancer treatment verify that the HAAA-NUs are superior photothermal agent for photothermal tumor ablation therapy owing to low toxicity and high cell destruction capability. [Copyright &y& Elsevier]

Abstract: In this work, we develop a multifunctional nano-platform by coating upconversion nanoparticles (UCNPs) with bovine serum albumin (BSA), obtaining UCNP@BSA nanoparticles with great solubility and stability in physiological environments. Two types of dye molecules, including a photosensitizer, Rose Bengal (RB), and an NIR-absorbing dye, IR825, can be simultaneously loaded into the BSA layer of the UCNP@BSA nanoparticles. In this carefully designed UCNP@BSA-RB&; IR825 system, RB absorbs green light emitted from UCNPs under 980-nm excitation to induce photodynamic cancer cell killing, while IR825 whose absorbance shows no overlap with upconversion excitation and emission wavelengths, offers nanoparticles a strong photothermal perform under 808-nm laser irradiation. Without showing noticeable dark toxicity, the obtained dual-dye loaded nanoparticles are able to kill cancer via combined photothermal and photodynamic therapies, both of which are induced by NIR light with high tissue penetration, by a synergetic manner both in vitro and in vivo. In addition, the intrinsic paramagnetic and optical properties of Gd3+-doped UCNPs can further be utilized for in vivo dual modal imaging. Our study suggests that UCNPs with well-designed surface engineering could serve as a multifunctional nano-platform promising in cancer theranostics. [Copyright &y& Elsevier]

Abstract: In recent years, graphene and graphene-based nanocomposites owning to their highly enriched physical and chemical properties have been widely explored for applications in many different fields including biomedicine. In the present work, we decorate graphene oxide (GO) by both iron oxide nanoparticles (IONPs) and gold, forming a multi-functional magnetic & plasmonic GO–IONP–Au nanocomposite with strong superparamagnetism and significantly enhanced optical absorbance in the near-infrared (NIR) region. We then coat the nanocomposite with polyethylene glycol (PEG), obtaining GO–IONP–Au–PEG with high stability in physiological environments and no significant in vitro toxicity. Remarkably enhanced photothermal cancer ablation effect using GO–IONP–Au–PEG is realized in comparison to PEGylated GO used in our earlier studies, as demonstrated in both in vitro cell tests and in vivo animal experiments. Moreover, the IONP and Au compartments in the GO–IONP–Au–PEG nanocomposite could be further taken advantages for magnetic resonance (MR) and X-ray dual-modal imaging. Our work shows the promise of using graphene-based multi-functional nanocomposite as cancer theranostics. [Copyright &y& Elsevier]

Abstract: Theranostics, the combination of diagnostics and therapies, has become a new concept in the battles with various major diseases such as cancer. Herein, we develop multifunctional nanoparticles (MFNPs) with highly integrated functionalities including upconversion luminescence, superparamagnetism, and strong optical absorption in the near-infrared (NIR) region with high photostability. In vivo dual modal optical/magnetic resonance imaging of mice uncovers that by placing a magnet nearby the tumor, MFNPs tend to migrate toward the tumor after intravenous injection and show high tumor accumulation, which is ∼8 folds higher than that without magnetic targeting. NIR laser irradiation is then applied to the tumors grown on MFNP-injected mice under magnetic tumor-targeting, obtaining an outstanding photothermal therapeutic efficacy with 100% of tumor elimination in a murine breast cancer model. We present here a strategy for multimodal imaging-guided, magnetically targeted physical cancer therapy and highlight the promise of using multifunctional nanostructures for cancer theranostics. [Copyright &y& Elsevier]

Abstract: Photothermal therapy as a physical treatment approach to destruct cancer has emerged as an alternative of currently used cancer therapies. Previously we have shown that polyethylene glycol (PEG) functionalized nano-graphene oxide (nGO-PEG) with strong optical absorption in the near-infrared (NIR) region was a powerful photothermal agent for in vivo cancer treatment. In this work, by using ultra-small reduced graphene oxide (nRGO) with non-covalent PEG coating, we study how sizes and surface chemistry affect the in vivo behaviors of graphene, and remarkably improve the performance of graphene-based in vivo photothermal cancer treatment. Owing to the enhanced NIR absorbance and highly efficient tumor passive targeting of nRGO-PEG, excellent in vivo treatment efficacy with 100% of tumor elimination is observed after intravenous injection of nRGO-PEG and the followed 808 nm laser irradiation, the power density (0.15 W/cm2, 5 min) of which is an order of magnitude lower than that usually applied for in vivo tumor ablation using many other nanomaterials. All mice after treatment survive over a period of 100 days without a single death or any obvious sign of side effect. Our results highlight that both surface chemistry and sizes are critical to the in vivo performance of graphene, and show the promise of using optimized nano-graphene for ultra-effective photothermal treatment, which may potentially be combined with other therapeutic approaches to assist our fight against cancer. [Copyright &y& Elsevier]

Abstract: Carbon nanotubes have shown great potential in various areas of biomedicine. Herein, we synthesize a series of amphiphilic polymers by anchoring polyethylene glycol (PEG) of different lengths at various densities on poly(maleic anhydride-alt-1-octadecene) (PMHC18). The blood circulation and biodistribution of those PEG-PMHC18-coated SWNTs in mice after intravenous injection are measured by an established Raman spectroscopy method. It is found that heavily PEGylated SWNTs with ultra-long blood circulation half-lives, although shows high uptake in the tumor, tend to accumulate in the skin dermis. A surface coating which affords SWNTs a blood half-life of 12–13 h appears to be optimal to balance the tumor-to-normal organ (T/N) uptake ratios of nanotubes in major organs. Using the selected SWNT conjugate, we then carry out a pilot in vivo photothermal therapy study and observe a promising cancer treatment efficacy. Our results highlight the importance of surface coating to the in vivo behaviors of nanomaterials in general and could provide guidelines to the future design of SWNT bioconjugates for various in vivo applications. [ABSTRACT FROM AUTHOR]

Gallium indium (GaIn) alloy as a kind of liquid metal (LM) with unique chemical and physical properties has attracted increasing attention for its potential biomedical applications. Herein, a series of core-shell GaIn@Metal (Metal: Pt, Au, Ag, and Cu) heterogeneous nanoparticles (NPs) are obtained by a simple in-situ reduction method. Take core-shell GaIn@Pt NPs for example, the synthesized GaIn@Pt NPs after Pt growth on their surface showed significantly improved photothermal conversion efficiency (PCE) and thermal stability under near-infrared (NIR) II light irradiation. Moreover, the core-shell GaIn@Pt NPs also exhibited good Fenton-like catalytic effect due to the presence of Pt on their surface, and could convert tumor endogenous H 2 O 2 to generate reactive oxygen species (ROS) for cancer cell killing. With biocompatible polyethylene glycol (PEG) modification, such GaIn@Pt-PEG NPs showed efficient tumor homing after intravenous injection, and could lead to effective NIR II triggered photothermal-chemodynamic synergistic therapy of tumors as evidenced in a mouse tumor model. Our work highlights the ingenious use of the chemical properties of metals, providing a rather simple route for the surface engineering of LM-based multifunctional nanoplatforms to achieve a variety of functionalities. Core-shell GaIn@Pt heterogeneous NPs prepared by in-situ reduction method were used for photothermal-enhanced catalytic therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

The rapid development of nanotechnology has triggered the emerging of tremendous theranostic nanoplatforms for combating cancers. Silicene, as an emerging two-dimensional (2D) material, has been recently explored as therapeutic agent due to their desirable biodegradation and strong photothermal-conversion performance. However, the rational design of silicene-based composites for further exerting multifunctional medical applications is still highly challenging. Herein, we report on the construction of silicene-based silicene@Pt composite nanosheets for computed tomography (CT)/photoacoustic (PA) imaging-guided dual-sensitized radiotherapy combined with photonic tumor hyperthermia, which has been achieved by a seed-growth approach to in situ grow Pt components onto silicene nanosheets' surface. Especially, by functionalization of Pt components, these nanosheets could act as both contrast agents for CT imaging and dual radio-sensitizing agents for radiotherapy, which could deposit Pt-involved radiation energy (sensitized therapeutic process I) and overcome hypoxia-associated radio-resistance by Pt-catalytic O 2 generation from overexpressed H 2 O 2 within the tumor microenvironment (sensitized therapeutic process II). The strong photothermal-conversion performance of silicene nanosheets not only endowed silicene@Pt composite nanosheets with photoacoustic imaging property, but also realized the photonic tumor hyperthermia and achieved a combined therapeutic effect with radiotherapy. This work not only broadens the biomedical applications of silicene, but also develops functionalization strategies of silicene for versatile biomedical applications. Image 1 [ABSTRACT FROM AUTHOR]

Nanoscale outer membrane vesicles (OMVs) secreted by Gram-negative bacteria are often applied in antibacterial treatment as adjuvants or antigens. Recently, OMVs have also been tested in a few anti-tumor treatment studies, in which OMVs are injected multiple times to achieve certain therapeutic effects, showing risks in repeated cytokine storms. Herein, we propose the use a single low dose of OMVs combined with photothermal therapy (PTT) for effective cancer treatment. It was found that single i. v. injection of OMVs could activate the immune system by boosting the secretion levels of anti-tumor related cytokines. In addition, single i. v. injection of OMVs could also lead to extravasation of red blood cells in the tumor mainly owing to the effect of lipopolysaccharide on the OMVs. Such effect was not observed in other normal organs. As the results, the tumors on OMV-treated mice showed obviously darkened color with greatly increased intratumoral optical absorbance in the near-infrared (NIR) region, further enabling effective photothermal ablation of those tumors by the NIR laser. Without causing obvious adverse responses, bacteria-derived OMVs may be a new type of therapeutic agent for cancer treatment with multiple functions. Image 1 [ABSTRACT FROM AUTHOR]

• Gold bipyramids with tunable surface plasmon resonance properties are synthesized. • The morphological yield is over 90% without any purification step. • Gold bipyramids exhibit high absorbance in 740–960 nm. • The functionalized gold bipyramids show great photothermal effect. • Gold bipyramids can be used as for imaging-guided cancer therapy. Monodisperse gold bipyramids (AuBPs) with controlled aspect ratio and tunable surface plasmon resonance (SPR) property have been synthesized using cetyltrimethylammonium bromide (CTAB) and sodium oleate (NaOL). The morphological yield of AuBPs is about 90% without any purification step. The presence of NaOL plays an important role in promoting the morphological yield of AuBPs by pre-reduce Au3+ to Au+. The obtained AuBPs exhibit strong absorbance in the near infrared region (NIR) that can be systematically tuned from 740 nm to 960 nm. After functionalized with polyethylene glycol (PEG), the as-prepared AuBPs have shown excellent photothermal stability and great biocompatibility, which could be used for high contrast computed tomography (CT) imaging and photothermal cancer therapy. This work provides not only a simple method for the synthesis of AuBPs with high morphological yield, but also a promising theranostic agent for cancer therapy. [ABSTRACT FROM AUTHOR]