One-step synthesis of multifunctional nanoparticles for CT/PA imaging guided breast cancer photothermal therapy.

Advances in nanotheranostics have promoted the development of precision medicine, which has great potential as a weapon for clinical diagnosis and therapy of tumors. However, the combination of three functional principle components (imaging probes, therapeutic agents and surface coating) in traditional theranostic system is difficult to be achieved in only one step, while undergoing multiple synthesis procedures, time-consuming process and unknown toxicity. Herein, we fabricated iodinated polyaniline (LC@I-PANi) nanoparticles via a facile one-step synthesis approach integrating chemical oxidative polymerization and iodine-doping process for computed tomography (CT) imaging and photoacoustic (PA) imaging-guided photothermal therapy (PTT). Iodic acid (HIO3) as an oxidant induces chemical oxidation polymerization of aniline monomers. Meanwhile, iodine is incorporated into the polyaniline structural units in the process of polymerization to obtain LC@I-PANi nanoparticles. Moreover, thel-cysteine (LC) has an effect on diameter of LC@I-PANi nanoparticles, which enables nanoparticles have size-controlled spherical morphology and good colloidal stability. The hemolysis assay and cytotoxicity assessment verified the good biocompatibility of LC@I-PANi. Moreover, our LC@I-PANi nanoparticles could not only exhibit appealing PTT efficiency, but also achieve excellent CT/PA dual-mode imaging effect. The histological evaluations suggested the negligible toxicity of LC@I-PANi in vivo. This is the first time to our knowledge that multifunctional LC@I-PANi nanoparticles were prepared by an ingenious one-step method. This work not only highlights a one-step strategy that simplified the complex synthesis of LC@I-PANi nanoparticles, but also provides insight for further biomedical application of "all-in-one" theranostic agent.

Coupling metal organic frameworks with molybdenum disulfide nanoflakes for targeted cancer theranostics.

The superior properties of metal organic frameworks (MOF) can provide great opportunities for merging functional nanoparticles to construct smart and versatile cancer theranostic agents. In this study, on the basis of non-mesoporous nanoparticles (molybdenum disulfide, MoS2), the structure of the MOF shell layer with an adjustable structure can be constructed through the natural coordination interaction between polydopamine (PDA) and iron ion, and the tumor cell target ligand was modified on the surface of the nanocomposite after loading the anticancer drug doxorubicin hydrochloride (DOX) to form a multifunctional cancer theranostics nanoplatform (DOX@MoS2-PMA). Benefiting from the excellent properties of MoS2 and MOF, the favorable photothermal properties and pH/near-infrared (NIR) laser-triggered DOX release behavior of composite nanoparticles were demonstrated. Its well-defined nanostructure, adequate colloidal stability, and satisfactory biocompatibility were further evidenced. Furthermore, the selective tumor cell targeting ability of DOX@MoS2-PMA can improve the cellular uptake efficacy and the photothermal-chemotherapy combination therapy can significantly enhance the killing effect on cancer cells both in vitro and in vivo. In addition, fluorescence imaging results show that nanoparticles can efficiently accumulate inside tumors. The photoacoustic (PA) and magnetic resonance (MR) imaging capabilities derived from different components of nanoparticles can perform better imaging effects. To the best of our knowledge, this is the first attempt to merge the performance of MoS2 with MOF for PA/MR dual-modality imaging-guided photothermal-chemotherapy combination therapy. Our work presented herein proves that MOF can be combined with non-mesoporous nanoparticles and exhibits excellent performance, thus opening a new avenue for endowing non-mesoporous nanoparticles with an efficient drug loading capacity and practical applications of MOFs in nanomedicine.

Polyethylenimine and sodium cholate-modified ethosomes complex as multidrug carriers for the treatment of melanoma through transdermal delivery.

Aim: Multidrug resistance is the main reason for the failure of chemotherapy during the treatment of the tumor. To overcome multidrug resistance, this study attempts to develop a novel transdermal drug-delivery system (TDDS) loading cytotoxic drug and chemosensitizer. Materials & methods: The polyethylenimine-modified ethosomes (Eth-PEI) and sodium cholate-modified ethosomes (Eth-SC) were firstly fabricated, and then a novel TDDS based on the carriers complex of Eth-PEI/Eth-SC was prepared by electrostatic interaction and evaluated both in vitro and in vivo. Results: The Eth-PEI/Eth-SC showed the excellent antitumor effect on treating melanoma, using doxorubicin and curcumin as the cytotoxic drug and chemosensitizer, respectively. Conclusion: The as-prepared TDDS composed of Eth-PEI/Eth-SC loading multidrug is an effective means for treating melanoma.

Merging metal organic framework with hollow organosilica nanoparticles as a versatile nanoplatform for cancer theranostics.

With great potential in nanomedicine, the integration of a metal organic framework (MOF) with a nanocarrier for smart and versatile cancer theranostics still seeks to expand. In this study, MOF was successfully merged with hollow mesoporous organosilica nanoparticles (HMONs) with a polydopamine (PDA) interlayer to form molecularly organic/inorganic hybridized nanocomposites (HMONs-PMOF). The well-defined nanostructure and favorable biocompatibility of HMONs-PMOF were demonstrated first. Doxorubicin hydrochloride (DOX) and indocyanine green (ICG) were separately loaded into the interior cavity of HMONs and the outer porous shell of MOF with high loading efficacy, respectively. The obtained dual drug-loaded nanocomposites (DI@HMONs-PMOF) displayed favorable photothermal properties and pH/NIR-triggered DOX release manner. Furthermore, in vitro cell experiments validated that HMONs-PMOF can efficiently deliver DOX into cancer cells. Upon entry into cancer cells, the photothermal effect of DI@HMONs-PMOF can induce the lysosome rupture, thereby facilitating the "lysosome escape" process and accelerating the DOX diffusion in the cytoplasm. Benefiting from the iron ion coordinated on PDA and ICG confined in MOF, magnetic resonance (MR) and photoacoustic (PA) dual-modality imaging were performed to verify the effective accumulation of DI@HMONs-PMOF at the tumor site. Interestingly, the results also suggested that the existence of ICG can cooperatively enhance the MR imaging capability of prepared nanocomposites. In addition, the significantly improved synergistic therapeutic efficacy was confirmed both in vitro and in vivo. Thus, our results indicated that the merged nanostructure of HMONs and MOF is promising for versatile cancer theranostics. STATEMENT OF SIGNIFICANCE: Metal organic framework (MOF) has recently emerged as a class of fascinating nanocarriers. The integration of MOF with other nanostructures can endow the new nanoformulation with collective functionality and synergistic performance that are not accessed from single-component nanostructure. Herein, we reported the successful merging of MOF and hollow mesoporous organosilica nanoparticles (HMONs) to form a hollow nanocontainer with a well-defined nanostructure. The large cavity of HMONs and highly porous network of MOF enable high drug loading efficacy. Moreover, the dual-modality magnetic resonance and photoacoustic imaging can be realized, which is also benefited from the merged nanostructure. Overall, we expected this paradigm could pave way for integrating MOF with other nanocarriers to achieve more diverse applications.

PEGylated (NH4)xWO3 nanorods as efficient and stable multifunctional nanoagents for simultaneous CT imaging and photothermal therapy of tumor.

The simultaneous imaging and photothermal therapy of tumors have attracted much attention, and a prerequisite is to obtain multifunctional nanomaterials. Ideally, one kind of nanoparticles with single component can be used as both imaging agent and photothermal agent. Herein, we have developed the PEGylated (NH4)xWO3 (denoted as (NH4)xWO3-PEG) nanorods as multifunctional nanoparticles with single semiconductor component. (NH4)xWO3-PEG nanorods with about 30nm diameter and length of several hundred nanometers have been obtained through a solvothermal synthesis-PEGylation two-step route. Under the irradiation of 980-nm laser with intensity of 0.72Wcm-2, aqueous dispersion of (NH4)xWO3-PEG nanorods (0.67-5.44mmol/L) displays high elevation (17.6-34.5°C) of temperature in 400s, accompanied by an excellent long-term photothermal stability. Furthermore, (NH4)xWO3-PEG nanorods exhibit as high as 6 times X-ray attenuation ability compared to that of the clinically used iodine-based X-ray computed tomography (CT) contrast agent (Iopromide). More importantly, after PBS solution of (NH4)xWO3-PEG nanorods is injected into the tumor of mice, the tumor can be effectively detected by CT imaging. Moreover, cancer cells in vivo can be further destroyed by the photothermal effects of (NH4)xWO3-PEG nanorods, under the irradiation of 980-nm laser with the safe intensity of 0.72Wcm-2 for 10min. Therefore, (NH4)xWO3-PEG nanorods can be used as a new kind of stable and efficient multifunctional nanoagent with single component for simultaneous CT imaging and photothermal therapy of tumor.

One-Pot Synthesis of MoS2 Nanoflakes with Desirable Degradability for Photothermal Cancer Therapy.

Developing biodegradable photothermal agent holds great significance for potential clinical translation of photothermal therapy. In the current study, one-pot hydrothermal synthesis of MoS2 nanoflakes with desirable degradation capability was presented. The participation of poly(acrylic acid) (PAA) in hydrothermal process could not only facilitate the modification of polyethylene glycol (PEG), but also bestow degradability to the prepared MoS2 nanoflakes. Moreover, the PEGylated hybrid nanoflakes (MoS2-PPEG) also exhibited excellent stability in various medium and outstanding photothermal properties. Interestingly, MoS2-PPEG behaved distinctly different degradation rate in diverse condition. The rapid degradation of MoS2-PPEG was observed in neutral pH solution, whereas much slower degradation occurred in an acidic tumor microenvironment. Furthermore, data indicated that the major degradation product of MoS2-PPEG was water-soluble Mo-based ion. Meanwhile, the good in vitro biocompatibility of MoS2-PPEG was also confirmed in terms of cytotoxicity and hemolysis. With favorable photothermal performance, MoS2-PPEG can efficiently killing cancer cells in vitro and suppress the tumor growth in vivo. More importantly, the gradual decreasing content of MoS2-PPEG in organs and detectable Mo element in urine of mice suggested that the degradability of MoS2-PPEG might facilitate its excretion to some degree. Hence, the degradable MoS2 nanoflakes prepared by one-pot hydrothermal routine may provide insight for further biomedical applications of inorganic photothermal agent.

Green electrospun grape seed extract-loaded silk fibroin nanofibrous mats with excellent cytocompatibility and antioxidant effect.

Silk fibroin (SF) from Bombyx mori has an excellent biocompatibility and thus be widely applied in the biomedical field. Recently, various SF-based composite nanofibers have been developed for more demanding applications. Additionally, grape seed extract (GSE) has been demonstrated to be powerful on antioxidation. In the present study, we dedicate to fabricate a GSE-loaded SF/polyethylene oxide (PEO) composite nanofiber by green electrospinning. Our results indicated the successful loading of GSE into the SF/PEO composite nanofibers. The introduction of GSE did not affect the morphology of the SF/PEO nanofibers and GSE can be released from the nanofibers with a sustained manner. Furthermore, comparing with the raw SF/PEO nanofibrous mats, the GSE-loaded SF/PEO nanofibrous mats significantly enhanced the proliferation of the skin fibroblasts and also protected them against the damage from tert-butyl hydroperoxide-induced oxidative stress. All these findings suggest a promising potential of this novel GSE-loaded SF/PEO composite nanofibrous mats applied in skin care, tissue regeneration and wound healing.

Flower-like PEGylated MoS2 nanoflakes for near-infrared photothermal cancer therapy.

Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS2) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS2 nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS2-PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation, and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS2-PEG nanoflakes under the irradiation. These results thus suggest that the MoS2-PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy.

Au/polypyrrole@Fe3O4 nanocomposites for MR/CT dual-modal imaging guided-photothermal therapy: an in vitro study.

Construction of multifunctional nanocomposites as theranostic platforms has received considerable biomedical attention. In this study, a triple-functional theranostic agent based on the cointegration of gold nanorods (Au NRs) and superparamagnetic iron oxide (Fe3O4) into polypyrrole was developed. Such a theranostic agent (referred to as Au/PPY@Fe3O4) not only exhibits strong magnetic property and high near-infrared (NIR) optical absorbance but also produces high contrast for magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Importantly, under the irradiation of the NIR 808 nm laser at the power density of 2 W/cm(2) for 10 min, the temperature of the solution containing Au/PPY@Fe3O4 (1.4 mg/mL) increased by about 35 °C. Cell viability assay showed that these nanocomposites had low cytotoxicity. Furthermore, an in vitro photothermal treatment test demonstrates that the cancer cells can be efficiently killed by the photothermal effects of the Au/PPY@Fe3O4 nanocomposites. In summary, this study demonstrates that the highly versatile multifunctional Au/PPY@Fe3O4 nanocomposites have great potential in simultaneous multimodal imaging-guided cancer theranostic applications.

In vitro and in vivo toxicity studies of copper sulfide nanoplates for potential photothermal applications.

Copper sulfide (CuS) has emerged as a promising photothermal agent. However, its potential toxic effects still remained poorly understood. Herein, CuS nanoplates were synthesized for toxicity assessment. The in vitro study indicated that the cell viability decreased when CuS nanoplate concentration was higher than 100 µg/mL. CuS nanoplates caused apparent toxicity to HUVEC and RAW 264.7 cells. For acute toxicity, maximum tolerated dose and lethal dose 50 were 8.66 and 54.5 mg/kg, respectively. Furthermore, the sub-chronic toxicity test results indicated that there was no obvious effect at tested doses during the test period. The biodistribution study showed that intravenously administrated CuS nanoplates were mainly present in the spleen, liver and lung. Taken together, our results shed light on the rational design of CuS nanomaterials to minimize toxicity, thus providing a useful guideline in selecting CuS as the photothermal agent for cancer therapy. FROM THE CLINICAL EDITOR: Photothermal ablation therapy is a promising new treatment modality for cancer. One of the potential photothermal agents is copper sulfide (CuS). In this article, the potential toxic effects of CuS nanoplates were studied. The authors showed that further modification on the design of CuS nanomaterials was needed to minimize toxicity.