Ligeng Xu

Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods.

Gold nanorods (Au NRs) have been recognized as promising materials for biomedical applications, like sensing, imaging, gene and drug delivery and therapy, but their toxicological issues are still controversial, especially for the Au NRs synthesized with seed-mediated method. In this study, we investigated the influence of aspect ratio and surface coating on their toxicity and cellular uptake. The cellular uptake is highly dependent on the aspect ratio and surface coating. However, the surface chemistry has the dominant roles since PDDAC-coated Au NRs exhibit a much greater ability to be internalized by the cells. The present data demonstrated shape-independent but coating-dependent cytotoxicity. Both the CTAB molecules left in the suspended solution and on the surface of Au NRs were identified as the actual cause of cytotoxicity. CTAB can enter cells with or without Au NRs, damage mitochondria, and then induce apoptosis. The effects of surface coating upon toxicity and cellular uptake were also examined using Au NRs with different coatings. When Au NRs were added into the medium, the proteins were quickly adsorbed onto the Au NRs that made the surface negatively charged. The surface charge may not directly affect the cellular uptake. We further demonstrated that the amount of serum proteins, especially for BSA, adsorbed on the Au NRs had a positive correlation with the capacity of Au NRs to enter cells. In addition, we have successfully revealed that the cationic PDDAC-coated Au NRs with an aspect ratio of 4 possess an ideal combination of both negligible toxicity and high cellular uptake efficiency, showing a great promise as photothermal therapeutic agents.

Selective targeting of gold nanorods at the mitochondria of cancer cells: Implications for cancer therapy

We have observed that Au nanorods (NRs) have distinct effects on cell viability via killing cancer cells while posing negligible impact on normal cells and mesenchymal stem cells. Obvious differences in cellular uptake, intracellular trafficking, and susceptibility of lysosome to Au NRs by different types of cells resulted in selective accumulation of Au NRs in the mitochondria of cancer cells. Their long-term retention decreased mitochondrial membrane potential and increased reactive oxygen species level that enhances the likelihood of cell death. These findings thus provide guidance for the design of organelle-targeted nanomaterials in tumor therapy.

Graphene oxide-silver nanocomposite as a highly effective antibacterial agent with species-specific mechanisms.

Recently, graphene oxide (GO) based nanocomposites have raised significant interests in many different areas, one of which being antibacterial agents where sliver nanoparticle (AgNPs) anchored GO (GO-Ag) has shown promising potential. However, to our best knowledge, factors affecting its antibacterial activity as well as the underlying mechanism remain unclear. In this study, we fabricate GO-Ag nanocomposites with different AgNPs to GO ratios and carefully investigate their antibacterial activities against both the Gram-negative (G-) bacteria Escherichia coli ( E. coli ) and the Gram-positive (G+) bacteria Staphylococcus aureus ( S. aureus ). We discover that, compared to AgNPs, GO-Ag nanocomposite with an optimal ratio of AgNPs to GO is much more effective and shows synergistically enhanced, strong antibacterial activities at rather low dose (2.5 μg/mL). The GO-Ag nanocomposite is more toxic to E. coli than that to S. aureus . The antibacterial effects of GO-Ag nanocomposite are further investigated, revealing distinct, species-specific mechanisms. The results demonstrate that GO-Ag nanocomposite functions as a bactericide against the G- E. coli through disrupting bacterial cell wall integrity, whereas it exhibits bacteriostatic effect on the G+ S. aureus by dramatically inhibiting cell division. Our work not only highlights the great promise of using GO-Ag as a highly effective antibacterial agent but also provides more in-depth understandings of the interactions between microorganisms and GO-based nanocomposites.

Surface-Engineered Gold Nanorods: Promising DNA Vaccine Adjuvant for HIV-1 Treatment

With the intense international response to the AIDS pandemic, HIV vaccines have been extensively investigated but have failed due to issues of safety or efficacy in humans. Adjuvants for HIV/AIDS vaccines are under intense research but a rational design approach is still lacking. Nanomaterials represent an obvious opportunity in this field due to their unique physicochemical properties. Gold nanostructures are being actively studied as a promising and versatile platform for biomedical application. Herein, we report novel surface-engineered gold nanorods (NRs) used as promising DNA vaccine adjuvant for HIV treatment. We have exploited the effects of surface chemistry on the adjuvant activity of the gold nanorod by placing three kinds of molecules, that is, cetyltrimethylammonium bromide (CTAB), poly(diallydimethylammonium chloride) (PDDAC), and polyethyleneimine (PEI) on the surface of the nanorod. These PDDAC- or PEI-modified Au NRs can significantly promote cellular and humoral immunity as well as T cell proliferation through activating antigen-presenting cells if compared to naked HIV-1 Env plasmid DNA treatment in vivo. These findings have shed light on the rational design of low-toxic nanomaterials as a versatile platform for vaccine nanoadjuvants/delivery systems.

Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

Conjugated polymers for photothermal therapy of cancer

Due to the high specificity, low side effects, and great efficacy, photothermal therapy using light energy to burn cancer has been proposed as an attractive alternative to traditional cancer therapies. In the recent few years, researchers have found that various conjugated polymers with strong absorbance in the near-infrared (NIR) window, if appropriately functionalized, could serve as highly effective photothermal agents, showing encouraging cancer ablation results both in vitro and in vivo. Those polymers could also be utilized as drug delivery carriers to load many aromatic therapeutic agents with high loading efficiencies, promising for combination cancer therapy. Thus, this mini-review article would discuss the latest progress in the development of conjugated polymers for photothermal therapy of cancer.

Graphene-Based Nanocomposite As an Effective, Multifunctional, and Recyclable Antibacterial Agent

The development of new antibacterial agents that are highly effective are of great interest. Herein, we present a recyclable and synergistic nanocomposite by growing both iron oxide nanoparticles (IONPs) and silver nanoparticles (AgNPs) on the surface of graphene oxide (GO), obtaining GO-IONP-Ag nanocomposite as a novel multifunctional antibacterial material. Compared with AgNPs, which have been widely used as antibacterial agents, our GO-IONP-Ag shows much higher antibacterial efficiency toward both Gram-negative bacteria Escherichia coli (E. coli) and Gram-positive bacteria Staphylococcus aureus (S. aureus). Taking the advantage of its strong near-infrared (NIR) absorbance, photothermal treatment is also conducted with GO-IONP-Ag, achieving a remarkable synergistic antibacterial effect to inhibit S. aureus at a rather low concentration of this agent. Moreover, with magnetic IONPs existing in the composite, we can easily recycle GO-IONP-Ag by magnetic separation, allowing its repeated use. Given the above advantages as well as its easy preparation and cheap cost, GO-IONP-Ag developed in this work may find potential applications as a useful antibacterial agent in the areas of healthcare and environmental engineering.

Hollow MnO 2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses

Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO2) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses. With hollow structures, H-MnO2 nanoshells post modification with polyethylene glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and a chemotherapy drug doxorubicin (DOX). The obtained H-MnO2-PEG/C&D would be dissociated under reduced pH within TME to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable in vivo synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Its further combination with checkpoint-blockade therapy would lead to inhibition of tumors at distant sites, promising for tumor metastasis treatment.MnO2 nanostructures are promising TME-responsive theranostic agents in cancer. Here, the authors develop a nano-platform based on hollow H-MnO2 nanoshells able to modulate the tissue microenvironment, release a drug and inhibit tumor growth alone or in combination with check-point blockade therapy.

Emerging nanomedicine approaches fighting tumor metastasis: animal models, metastasis-targeted drug delivery, phototherapy, and immunotherapy

Metastasis is directly or indirectly responsible for the majority of cancer deaths. Anti-metastasis treatment is thus the key to cure cancer. Recent development in nanomedicine has shown great promise for tackling cancer metastasis. In recent years, nanoparticle-based drug delivery systems have been extensively explored for improving cancer treatment, showing the ability to reduce the risk of tumor metastasis compared with conventional chemotherapy. Photothermal therapy, by employing nano-theranostic agents, has also been found to be able to inhibit lymphatic tumor metastasis. Moreover, the post-immunological effects of certain types of nano-therapies may also be utilized to treat tumor metastasis, presenting an exciting new avenue towards successful cancer treatment. In this review article, we would like to summarize the latest research advances in the development of various emerging nanomedicine approaches for cancer metastasis treatment, and discuss future prospects in this emerging field as well as the clinical translation potential of these techniques.

Antigen-Loaded Upconversion Nanoparticles for Dendritic Cell Stimulation, Tracking, and Vaccination in Dendritic Cell-Based Immunotherapy

A dendritic cell (DC) vaccine, which is based on efficient antigen delivery into DCs and migration of antigen-pulsed DCs to draining lymph nodes after vaccination, is an effective strategy in initiating CD8(+) T cell immunity for immunotherapy. Herein, antigen-loaded upconversion nanoparticles (UCNPs) are used to label and stimulate DCs, which could be precisely tracked after being injected into animals and induce an antigen-specific immune response. It is discovered that a model antigen, ovalbumin (OVA), could be adsorbed on the surface of dual-polymer-coated UCNPs via electrostatic interaction, forming nanoparticle-antigen complexes, which are efficiently engulfed by DCs and induce DC maturation and cytokine release. Highly sensitive in vivo upconversion luminescence (UCL) imaging of nanoparticle-labeled DCs is successfully carried out, observing the homing of DCs to draining lymph nodes after injection. In addition, strong antigen-specific immune responses including enhanced T cell proliferation, interferon gamma (IFN-γ) production, and cytotoxic T lymphocyte (CTL)-mediated responses are induced by a nanoparticle-pulsed DC vaccine, which is promising for DC-based immunotherapy potentially against cancer.