PEGylated fullerene/iron oxide nanocomposites for photodynamic therapy, targeted drug delivery and MR imaging.

Recently, fullerene and fullerene derivatives owning to their highly enriched physical and chemical properties have been widely explored for applications in many different fields including biomedicine. In this study, iron oxide nanoparticles (IONPs) were decorated onto the surface of fullerene (C60), and then PEGylation was performed to improve the solubility and biocompatibility of C60-IONP, obtaining a multi-functional C60-IONP-PEG nanocomposite with strong superparamagnetism and powerful photodynamic therapy capacity. Hematoporphyrin monomethyl ether (HMME), a new photodynamic anti-cancer drug, was conjugated to C60-IONP-PEG, forming a C60-IONP-PEG/HMME drug delivery system, which demonstrated an excellent magnetic targeting ability in cancer therapy. Compared with free HMME, remarkably enhanced photodynamic cancer cell killing effect using C60-IONP-PEG/HMME was realized not only in a cultured B16-F10 cells in vitro but also in an in vivo murine tumor model due to 23-fold higher HMME uptake of tumor and strong photodynamic activity of C60-IONP-PEG. Moreover, C60-IONP-PEG could be further used as a T2-contrast agent for in vivo magnetic resonance imaging. Our work showed C60-IONP-PEG/HMME had a great potential for cancer theranostic applications.

Shi J ，Yu X ，Wang L ，Liu Y ，Gao J ，Zhang J ，Ma R ，Liu R ，Zhang Z ... -  《-》

A fullerene-based multi-functional nanoplatform for cancer theranostic applications.

Recently, nanomaterials with multiple functions, such as drug carrier, MRI and optical imaging, photothermal therapy etc, have become more and more popular in the domain of cancer research. In this study, a C60-IONP nanocomposite is synthesized via decorating iron oxide nanoparticles (IONP) onto fullerene (C60) and then functionalized by polyethylene glycol (PEG2000), giving C60-IONP-PEG with excellent stability in physiological solutions, finally folic acid (FA), a widely used tumor targeting molecule, was linked to C60-IONP-PEG in order to obtain an active tumor targeting effect to MCF-7 cells and malignant tumor in mice models. Herein, a hybrid nanoplatform with multi-functional characteristics for cancer diagnosis, photodynamic therapy (PDT), radiofrequency (RF) thermal therapy (RTT) and magnetic targeting applications was developed and explored its biofunctions in vitro and in vivo. C60-IONP-PEG-FA showed neglectable toxicity, not only served as a powerful tumor diagnostic magnetic resonance imaging (MRI) contrast agent, but also as a strong photosensitizer and powerful agent for photothermal ablation of tumor, furthermore a remarkable synergistic enhancement of PDT combination with RTT was also observed during the treatment both in vitro and in vivo. Moreover, the multi-functional nanoplatform also could selectively kill cancer cells in highly localized regions via the excellent active tumor targeting and magnetic targeted abilities. This work showed the multi-functional C60-IONP-PEG-FA nanoplatform had a great potential for cancer theranostic applications.

Shi J ，Wang L ，Gao J ，Liu Y ，Zhang J ，Ma R ，Liu R ，Zhang Z ... -  《-》

A tumor-specific cleavable nanosystem of PEG-modified C60@Au hybrid aggregates for radio frequency-controlled release, hyperthermia, photodynamic therapy and X-ray imaging.

Taking advantages of fullerene (C60) and gold nanoparticles (AuNPs) for potentials in photodynamic therapy (PDT), drug delivery and radio frequency thermal therapy (RTT), a C60@Au hybrid nanocomposite was synthesized by chemical deposition of Au nanoparticles onto C60, and functionalized by PEG5000 via a pH cleavable hydrazone bond, making C60@Au-PEG keep the PEG on the surface of drug delivery system during circulation but dissociate PEG from the system after accumulation in tumor tissue, then doxorubicin (DOX) was loaded onto C60@Au-PEG with a very high drug loading efficiency. The release profiles of DOX from C60@Au-PEG/DOX showed strong dependences on radio frequency (RF). For the drug delivery, C60@Au-PEG/DOX afforded much higher antitumor efficacy owing to 8.6-fold higher DOX uptake of tumor than DOX. Besides, in this work, C60@Au-PEG/DOX not only served as a powerful RTT agent for RF-thermal ablation of tumor and a strong photosensitizer (PS) for PDT, but also as an X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, C60@Au-PEG/DOX showed excellent chemo-RF thermal-photodynamic therapeutic efficacy, RF-controlled drug releasing function, tumor targeting property, tumoral acid PEG dissociating character and X-ray imaging ability, demonstrating that there is a great potential of C60@Au-PEG/DOX for simultaneous diagnosis and therapy in cancer treatment. A significant challenge in cancer therapy is to maximize the therapeutic efficacy and minimize the side effects. In the past decade, a lot of nanoparticles have been used as the carriers for efficient drug delivery. However, the design of drug delivery system (DDS) with stimuli-responsive controlled-release property, simultaneous diagnosis and therapy functions is still a challenge. Herein, we developed a new drug delivery system (C60@Au-PEG/DOX), and explored its applications in tumor therapy. The in vitro and in vivo results showed C60@Au-PEG/DOX could significantly improve the therapeutic efficacy and reduce the systemic toxicity through X-ray imaging guided locatable DOX release, photodynamic and photothermal therapies. These results are of interest as they demonstrate a multi-functional DDS for tumor theranostic applications.

Shi J ，Chen Z ，Wang L ，Wang B ，Xu L ，Hou L ，Zhang Z ... -  《-》

Graphene-based magnetic plasmonic nanocomposite for dual bioimaging and photothermal therapy.

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.

Shi X ，Gong H ，Li Y ，Wang C ，Cheng L ，Liu Z ... -  《-》

Drug/Dye-Loaded, Multifunctional PEG-Chitosan-Iron Oxide Nanocomposites for Methotraxate Synergistically Self-Targeted Cancer Therapy and Dual Model Imaging.

Lin J ，Li Y ，Li Y ，Wu H ，Yu F ，Zhou S ，Xie L ，Luo F ，Lin C ，Hou Z ... -  《-》