Loading and delivery of Bcl‐2‐targeted short interfering RNA (siRNA) and anticancer drug doxorubicin (DOX) by polyethylenimine (PEI)‐conjugated graphene oxide (PEI‐GO) is studied. A higher knockdown efficiency of siRNA delivered by PEI‐GO than by PEI is achieved. Sequential delivery of siRNA and DOX by the PEI‐GO nanocarrier shows a synergistic effect, which leads to significantly improved chemotherapy efficacy.

Single stranded ribonucleic acid (ssRNA) acts as a probe, antisense (AS), miRNA analog and inhibitor, and is promising for gene therapy and molecular diagnosis. However, free ssRNA exhibits poor cellular uptake due to its negative charges, and enzyme instability, which have largely limited the practical applications of ssRNA in biomedicine. To address these issues, we have developed a PEGylated reduced graphene oxide (PEG-RGO) nanovector for efficient delivery of ssRNA. We have demonstrated that PEG-RGO exhibits superior ssRNA loading and delivery capability, compared to the widely studied PEGylated graphene oxide (PEG-GO). Computational simulation further suggested that PEG-RGO binds ssRNA much stronger than PEG-GO, consistent with the experimental results. These results will have implications in designing RGO-based biocompatible and efficient ssRNA delivery systems.

Although gold nanorods (GNRs) have been prepared with a wide range of methods for their uses as novel diagnostic and therapeutic agents, the synthesis of monodispersed GNRs with high yields and size tunability still requires further improvements. We report on a simple one-pot method for preparing highly monodispersed GNRs using phenols (e.g., hydroquinone, 1,2,3-trihydroxybenzene, and 1,2,4-trihydroxybenzene) as the reducing agent and NaBH 4 as the initiating reactant. Finetuning of the LSPR peak position of phenols-reduced GNRs from 550 to 1150 nm is accomplished by regulating the silver ion concentrations. The size of GNRs produced via phenols reduction can also be controlled by changing the NaBH 4 concentration. By systematically optimizing the concentrations of the reagents involved in the one-pot synthesis of GNRs, the yield (in many cases exceeding 90%) is significantly higher than that prepared with the commonly used reductant (e.g., ascorbic acid). The improved efficiency and controllability cut down the cost and time involved in GNRs production.

MicroRNAs (miRNAs) are key biological regulators and promising disease markers whose detection technologies hold great potentials in advancing fundamental research and medical diagnostics. Currently, miRNAs in biological samples have to be labeled before being applied to most high-throughput assays. Although effective, these labeling-based approaches are usually labor-intensive, time-consuming and liable to bias. Besides, the cross-hybridization of co-existing miRNA precursors (pre-miRNAs) is not adequately addressed in most assays that use total RNA as input. Here, we present a hybridization-triggered fluorescence strategy for label-free, microarray-based high-throughput miRNA expression profiling. The total RNA is directly applied to the microarray with a short fluorophore-linked oligonucleotide Universal Tag which can be selectively captured by the target-bound probes via base-stacking effects. This Stacking-Hybridized Universal Tag (SHUT) assay has been successfully used to analyze as little as 100 ng total RNA from human tissues, and found to be highly specific to homogenous miRNAs. Superb discrimination toward single-base mismatch at the 5′ or 3′ end has been demonstrated. Importantly, the pre-miRNAs generated negligible signals, validating the direct use of total RNA.

In this communication, preparation of graphene quantum dots (GQDs) with size about 10 nm by vigorous oxidation of graphite is reported. Thus obtained GQDs exhibit good physiological solubility, high photostability, low cytotoxicity, and yellow-green fluorescence with quantum yield about 7%. Furthermore, the feasibility of the GQDs for cell imaging application is demosntrated.

We have developed a fluorescence quenching based approach using graphene oxide (GO) for rapid detection of miRNAs. This GO-based method has been demonstrated to be highly specific to homogenous miRNAs, and is reverse transcription free which simplifies the detection procedures and reduces the total analysis time and cost.

Immunogenic cell death (ICD) is a specific kind of cell death that stimulates the immune system to combat cancer cells. Ultrasound (US)-controlled targeted release of drugs by liposome-microbubble complexes is a promising approach due to its non-invasive nature and visibility through ultrasound imaging. However, it is not known whether this approach can enhance ICD induced by drugs, such as doxorubicin. Herein, we prepared a doxorubicin-liposome-microbubble complex (MbDox), and the resultant MbDox was then characterized and tested for US-controlled release of Dox (MbDox+US treatment) to enhance the induction of ICD in LL/2 and CT26 cancer cells and in syngeneic murine models. We found that MbDox+US treatment caused more cellular uptake and nuclear accumulation of Dox in tumor cells, and more accumulation of Dox in tumor tissues. Enhanced induction of ICD occurred both and. MbDox+US treatment induced more apoptosis, stronger membrane exposure and the release of ER stress proteins and DAMPs in tumor cells, and increased DC maturation . In addition, MbDox+US treatment also resulted in stronger therapeutic effects in immunocompetent mice than in immunodeficient mice. Moreover, MbDox+US enhancement of ICD was also evidenced by a higher proportion of activated CD8 T-lymphocytes but lower Treg in tumor tissues. Taken together, our results demonstrate that US-controlled release of ICD inducers into nuclei using liposome-microbubble complexes may be an effective approach to enhance the induction of ICD for tumor treatment.

Traditional chemo‐immunotherapy can elicit T cell immune response by inducing immunogenic cell death (ICD), however, insufficient ICD limits the lasting antitumor immunotherapeutic efficacy. Herein, tadpole–ovoid manganese‐doped hollow mesoporous silica coated gold nanoparticles (Au@HMnMSNs) as biodegradable catalytic cascade nanoreactors are constructed to generate intratumoral high‐toxic hydroxyl radicals combined with DOX and Aspirin (ASA) for enhancing the induction of ICD and maturation of dendritic cells (DCs). The released Mn2+ can catalyze endogenous H2O2 to hydroxyl radicals, while internal gold nanoparticles mimetic glucose oxidase (GOx) converted glucose into H2O2 to accelerate the generation of hydroxyl radicals. On the other hand, tadpole oval‐structured Au@HMnMSNs can avoid the inactivation of gold nanoparticles due to strong protein adsorption. The introduction of ASA is to recruit DCs and cytotoxic T lymphocytes (CTLs) to tumor sites and restrain the intratumoral infiltration of immunosuppressive cells by decreasing the expression of prostaglandin E2 (PGE2). Accordingly, this work presents a novel insight to introduce GOx‐like catalytic cascade ICD nano‐inducer into antitumor immunotherapy for synergistic tumor therapy.