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Activatable imaging probes are promising to achieve increased signal-to-noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a non-invasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from the metal ion-associated potential long-term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH-responsive polymer and gadolinium metallofullerene (GMF). This GMF-based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH-responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic-to-hydrophilic conversion of the pH-responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.

We have developed a one-step nucleic acid dipstick assay (NADA) for visually detecting polymerase chain reaction (PCR) products within 3min. "One-step" means that there were no additional procedures between amplification and detection.This method was achieved through the use of asymmetric PCR and specially designed probes with appropriate melting temperature values. We initially combined one-step NADA with asymmetric capillary convective PCR (ACCPCR), an easy and rapid nucleic acid amplification technique, to construct an on-site nucleic acid diagnostic platform.We developed a diagnostic assay for the hepatitis B virus based on the ACCPCR-NADA platform to verify its feasibility. It exhibited an analytical sensitivity of three copies per test and a broad detection spectrum including genotype A-I. It also showed 97.9% sensitivity and 100% specificity based on the results observed using 67 serum samples with the Roche COBAS AmpliPrep/COBAS TaqMan (COBAS) system as the standard for comparison.The results provide evidence for the feasibility of using an ACCPCR-NADA platform in practical applications, especially in on-site test.

This paper describes a rapid diagnostic platform for pathogen detection based on the acetylcholinesterase-catalyzed hydrolysis reaction. Owing to the signal amplification strategies, the sensitivity of this assay is comparable to that of PCR. In addition, the readout of this assay is based on the color change of solutions, which can be easily observed by the naked eye alone.

Molecular design of biomaterials with unique features recapitulating nature's niche to influence biological activities has been a prolific area of investigation in chemistry and material science. The extracellular matrix (ECM) provides a wealth of bioactive molecules in supporting cell proliferation, migration, and differentiation. The well-patterned fibril and intertwining architecture of the ECM profoundly influences cell behavior and development. Inspired by those features from the ECM, we attempted to integrate essential biological factors from the ECM to design bioactive molecules to construct artificial self-supportive ECM mimics to advance stem cell culture. The synthesized biomimic molecules are able to hierarchically self-assemble into nanofibril hydrogels in physiological buffer driven by cooperative effects of electrostatic interaction, van der Waals forces, and intermolecular hydrogen bonds. In addition, the hydrogel is designed to be degradable during cell culture, generating extra space to facilitate cell migration, expansion, and differentiation. We exploited the bioactive hydrogel as a growth-factor-free scaffold to support and accelerate neural stem cell adhesion, proliferation, and differentiation into functional neurons. Our study is a successful attempt to entirely use bioactive molecules for bottom-up self-assembly of new biomaterials mimicking the ECM to directly impact cell behaviors. Our strategy provides a new avenue in biomaterial design to advance tissue engineering and cell delivery.

Photodynamic therapy (PDT) is an efficacious treatment for some types of cancers. However, PDT-induced tumor hypoxia as a result of oxygen consumption and vascular damage can reduce the efficacy of this therapy. Measuring and monitoring intrinsic and PDT-induced tumor hypoxia in vivo during PDT is of high interest for prognostic and treatment evaluation. In the present study, static and dynamic 18F-FMISO PET were performed with mice bearing either U87MG or MDA-MB-435 tumor xenografts immediately before and after PDT at different time points. Significant difference in tumor hypoxia in response to PDT over time was found between the U87MG and MDA-MB-435 tumors in both static and dynamic PET. Dynamic PET with pharmacokinetics modeling further monitored the kinetics of 18F-FMISO retention to hypoxic sites after treatment. The Ki and k3 parametric analysis provided information on tumor hypoxia by distinction of the specific tracer retention in hypoxic sites from its non-specific distribution in tumor. Dynamic 18F-FMISO PET with pharmacokinetics modeling, complementary to static PET analysis, provides a potential imaging tool for more detailed and more accurate quantification of tumor hypoxia during PDT.

We report a simple method to convert RBCs into efficient microreactors for important biomedical applications. A commonly used cell membrane permeation agent Triton X-100 (TX) was employed at finely tuned concentrations to punch pores in the membranes and render RBCs highly permeable to substrates while maintaining membrane integrity. Subsequently, low concentration of the fixative agent glutaraldehyde (GA) was used to stabilize the cells and avoid inactivation of the membrane proteins. Atomic force microscopy (AFM) and measurement of Young’s modulus (YM) values clearly demonstrated that the reformed RBCs (Ref-RBCs) retained their size, the biconcave disk-like shape, elasticity, and mechanical flexibility comparable to natural RBCs. Furthermore, Ref-RBCs improve the blood survival time of loaded enzymes, and have high permeability to substrate molecules. By exploiting these properties of Ref-RBCs microreactors, we developed an important biomedical application of blood detoxification. When uric acid (UA) and KCN were used as endogenous and exogenous toxin models, respectively, Ref-RBCs, loaded with the corresponding detoxifying enzymes, showed much faster toxin clearance rates than the unmodified RBCs both in vitro and in an in vivo animal model. Our results suggest that these microreactors, after confirming biocompatibility, would have promising therapeutic applications, especially in blood and liver-related diseases.

Nanomedicines have been demonstrated to have passive or active tumor targeting behaviors, which are promising for cancer chemotherapy. However, most nanomedicines still suffer from a suboptimal targeting effect and drug leakage, resulting in unsatisfactory treatment outcome. Herein, a hierarchical responsive nanomedicine (HRNM) is developed for programmed delivery of chemotherapeutics. The HRNMs are prepared via the self-assembly of cyclic Arg-Gly-Asp (RGD) peptide conjugated triblock copolymer, poly(2-(hexamethyleneimino)ethyl methacrylate)-poly(oligo-(ethylene glycol) monomethyl ether methacrylate)-poly[reduction-responsive camptothecin] (PC7A-POEG-PssCPT). In blood circulation, the RGD peptides are shielded by the POEG coating; therefore, the nanosized HRNMs can achieve effective tumor accumulation through passive targeting. Once the HRNMs reach a tumor site, due to the hydrophobic-tohydrophilic conversion of PC7A chains induced by the acidic tumor microenvironment, the RGD peptides will be exposed for enhanced tumor retention and cellular internalization. Moreover, in response to the glutathione inside cells, active CPT drugs will be released rapidly for chemotherapy. The in vitro and in vivo results confirm effective tumor targeting, potent antitumor effect, and reduced systemic toxicity of the HRNMs. This HRNM is promising for enhanced chemotherapeutic delivery.

Engineering functional nanomaterials with high therapeutic efficacy and minimum side effects has increasingly become a promising strategy for cancer treatment. Herein, a reactive oxygen species (ROS) enhanced combination chemotherapy platform is designed via a biocompatible metal-polyphenol networks self-assembly process by encapsulating doxorubicin (DOX) and platinum prodrugs in nanoparticles. Both DOX and platinum drugs can activate nicotinamide adenine dinucleotide phosphate oxidases, generating superoxide radicals (O2•- ). The superoxide dismutase-like activity of polyphenols can catalyze H2 O2 generation from O2•- . Finally, the highly toxic HO• free radicals are generated by a Fenton reaction. The ROS HO• can synergize the chemotherapy by a cascade of bioreactions. Positron emission tomography imaging of 89 Zr-labeled as-prepared DOX@Pt prodrug Fe3+ nanoparticles (DPPF NPs) shows prolonged blood circulation and high tumor accumulation. Furthermore, the DPPF NPs can effectively inhibit tumor growth and reduce the side effects of anticancer drugs. This study establishes a novel ROS promoted synergistic nanomedicine platform for cancer therapy.

Histone deacetylase 10 (HDAC10) is a member of the class II HDACs, and its role in cancer is emerging. In this study, we found that HDAC10 is highly expressed in lung cancer tissues. It resides mainly in the cytoplasm of lung cancer cells but resides in the nucleus of adjacent normal cells. Further examinations revealed that HDAC10 resides in the cytoplasm in multiple lung cancer cell lines, including the A549, H358 and H460 cell lines, but mainly resides in the nucleus of normal lung epithelial 16HBE cells. A leucine-rich motif, R505L506L507C508V509A510L511, was identified as its nuclear localization signal (NLS), and a mutant (Mut-505-511) featuring mutations to A at each of its original R and L positions was found to be nuclear-localization defective. Functional analysis revealed that HDAC10 promoted lung cancer cell growth and that its knockdown induced cell cycle arrest and apoptosis. Mechanistic studies showed that HDAC10 knockdown significantly decreased the phosphorylation of AKT at Ser473 and that AKT expression significantly rescued the cell cycle arrest and apoptosis elicited by HDAC10 knockdown. A co-immunoprecipitation assay suggested that HDAC10 interacts with AKT and that inhibition of HDAC10 activity decreases its interaction with and phosphorylation of AKT. Finally, we confirmed that HDAC10 promoted lung cancer proliferation in a mouse model. Our study demonstrated that HDAC10 localizes and functions in the cytoplasm of lung cancer cells, thereby underscoring its potential role in the diagnosis and treatment of lung cancer.

It is a critically important challenge to rapidly design effective vaccines to reduce the morbidity and mortality of unexpected pandemics. Inspired from the way that most enveloped viruses hijack a host cell membrane and subsequently release by a budding process that requires cell membrane scission, we genetically engineered viral antigen to harbor into cell membrane, then form uniform spherical virus-mimetic nanovesicles (VMVs) that resemble natural virus in size, shape, and specific immunogenicity with the help of surfactants. Incubation of major cell membrane vesicles with surfactants generates a large amount of nano-sized uniform VMVs displaying the native conformational epitopes. With the diverse display of epitopes and viral envelope glycoproteins that can be functionally anchored onto VMVs, we demonstrate VMVs to be straightforward, robust and tunable nanobiotechnology platforms for fabricating antigen delivery systems against a wide range of enveloped viruses.

Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released-Gd-ions-associated toxicity. Herein, a radionuclide-64 Cu-labeled doxorubicin-loaded polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging-guided combination cancer therapy. In this system, the near-infrared (NIR)-absorbing PDA acts as a platform for the assembly of different moieties; Gd3 N@C80 , a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as-prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r 1 = 14.06 mM-1 s-1 ), low risk of release of Gd ions, and NIR-triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo-photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.

The combination of gold and copper is a good way to pull down the cost of gold and ameliorate the instability of copper. Through shape control, the synergy of these two metals can be better exploited. Here, we report an aqueous phase route to the synthesis of pentacle gold–copper alloy nanocrystals with fivefold twinning, the size of which can be tuned in the range from 45 to 200 nm. The growth is found to start from a decahedral core, followed by protrusion of branches along twinning planes. Pentacle products display strong localized surface plasmon resonance peaks in the near-infrared region. Under irradiation by an 808-nm laser, 70-nm pentacle nanocrystals exhibit a notable photothermal effect to kill 4T1 murine breast tumours established on BALB/c mice. In addition, 70-nm pentacle nanocrystals show better catalytic activity than conventional citrate-coated 5-nm Au nanoparticles towards the reduction of p-nitrophenol to p-aminophenol by sodium borohydride., Control over the size and shape of nanostructures is important for many applications but challenging, especially for bimetallic systems. Here, the authors report the size-controlled synthesis of star-shaped gold–copper nanocrystals and show their applications in catalysis and photothermal therapy.

Ultrasensitive and quantitative detection of cancer biomarkers is an unmet challenge because of their ultralow concentrations in clinical samples. Although gold nanoparticle (AuNP)-based immunoassays offer high sensitivity, they were unable to quantitatively detect targets of interest most likely due to their very narrow linear ranges. This article describes a quantitative colorimetric immunoassay based on glucose oxidase (GOx)-catalyzed growth of 5 nm AuNPs that can detect cancer biomarkers from attomolar to picomolar levels. In addition, the limit of detection (LOD) of prostate-specific antigen (PSA) of this approach (93 aM) exceeds that of commercial enzyme-linked immunosorbent assay (ELISA) (6.3 pM) by more than 4 orders of magnitude. The emergence of red or purple color based on enzyme-catalyzed growth of 5 nm AuNPs in the presence of target antigen is particularly suitable for point-of-care (POC) diagnostics in both resource-rich and resource-limited settings.

The diagnosis and treatment of cancer have been greatly improved with the recent developments in molecular imaging. One of the promising molecular imaging tools for cancer diagnosis and treatment is fluorescence imaging. Fluorescence imaging probes can be functionalized with targeting moieties and therapeutic agents, provide new potentials for clinical diagnostics and therapies, and will undoubtedly play a critical role in cancer therapy. In this chapter, we focus on the recent outcome of basic studies in the design of new near-infrared fluorescent probes used for fluorescence imaging-guided cancer diagnosis and treatment.

It is still in high demand to develop extremely sensitive and accurate clinical tools for biomarkers of interest for early diagnosis and monitoring of diseases. In this report, we present a highly sensitive and compatible gold nanoparticle (AuNP)-based fluorescence activatable probe for sensing ultra-low levels of prostate-specific antigen (PSA) in patient serum samples. The limit of detection of the newly-developed probe for PSA was pushed down to 0.032 pg/mL, which is more than two orders of magnitude lower than that of the conventional fluorescence probe. The ultrahigh sensitivity of this probe was attributed to the high loading efficiency of the dyes on AuNP surfaces and high fluorescence quenching unquenching abilities of the dye-AuNP pairs. The efficiency and robustness of this probe was investigated in patient serum samples, demonstrating the great potential of this probe in real-world applications.