Huirong Lin

Tumor Microenvironment-Triggered Supramolecular System as an In Situ Nanotheranostic Generator for Cancer Phototherapy

The efficacy of photosensitizers in cancer phototherapy is often limited by photobleaching, low tumor selectivity, and tumor hypoxia. Assembling photosensitizers into nanostructures can improve photodynamic therapy efficacy and the safety profile of photosensitizers. Herein by employing supramolecular assembly, enhanced theranostic capability of Mn2+ -assisted assembly of a photosensitizer (sinoporphyrin sodium, DVDMS) is demonstrated. A tumor environment-triggered coassembly strategy is further developed to form Mn/DVDMS nanotheranostics (nanoDVD) for cancer phototherapy. MnO2 nanosheets serve as a highly effective DVDMS carrier and in situ oxygen and nanoDVD generator. In MCF-7 cells and xenograft tumors, MnO2 /DVDMS is reduced by glutathione (GSH) and H2 O2 and reassembled into nanoDVD, which can be monitored by activated magnetic resonance/fluorescence/photoacoustic signals. Intriguingly, the decrease of GSH, the production of O2 , and the formation of nanoDVD are shown to be synergistic with phototherapy to improve antitumor efficacy in vitro and in vivo, offering a new avenue for cancer theranostics.

Genetically Engineered Liposome‐like Nanovesicles as Active Targeted Transport Platform

Ligand-targeted delivery of drug molecules to various types of tumor cells remains a major challenge in precision medicine. Inspired by the secretion process and natural cargo delivery functions of natural exosomes, biomimetic synthetic strategies are exploited to prepare biofunctionalized liposome-like nanovesicles (BLNs) that can artificially display a wide variety of targeting protein/peptide ligands and directly encapsulate medical agents for enhanced drug delivery. Here, as a proof of concept, genetically engineered BLNs, which display human epidermal growth factor (hEGF) or anti-HER2 Affibody as targeting moieties, are developed to, respectively, target two types of tumor cells. Notably, in comparison to synthetic liposomes covalently coupled with hEGF, it is demonstrated in this work that biosynthetically displayed hEGF ligands on BLNs possess higher biological activities and targeting capabilities. Additionally, treatments with doxorubicin-loaded BLNs displaying Affibody ligands exhibit much better antitumor therapeutic outcomes than clinically approved liposomal doxorubicin (Doxil) in HER2-overexpressing BT474 tumor xenograft models. These data suggest that BLN is suitable as a potent surrogate for conventional proteoliposomes or immunoliposomes as a result of excellent targeting capacities and facile production of BLNs.

Enzyme-free colorimetric determination of EV71 virus using a 3D-MnO2-PEG nanoflower and 4-MBA-MA-AgNPs

We present a simple colorimetric assay for EV71 virus detection based on the aggregation of 4-mercaptobenzoic acid (4-MBA) and melamine (MA) modified silver nanoparticles (4-MBA-MA-AgNPs) in the presence of Mn2+. The EV71-Ab1 was incubated on a 96-well plate and the EV71-Ab2 was labeled on the surface of three-dimensional nanoflower-like MnO2-PEG (3D-MnO2-PEG). After layer-by-layer immunoreactions, the EV71 virus and the corresponding 3D-MnO2-PEG-Ab2 were captured on the plate. With the addition of Vitamin C (Vc), Mn2+ was released from the 3D-MnO2-PEG and then the aggregation of the 4-MBA-MA-AgNPs was induced, allowing a naked-eye detection limit of EV71 virus to be as low as 5 × 104 particles per mL, which is about three orders of magnitude lower than the conventional enzyme-linked immunosorbent assay (ELISA). This enzyme-free immunoassay based on a hybrid 3D-MnO2 features signal amplification strategies via a simple reduction reaction.

A Single-step Multi-level Supramolecular System for Cancer Sonotheranostics

A multi-level supramolecular system produced by single-step Fe3+-mediated ionic crosslinking self-assembly can overcome the critical issues of current sonodynamic therapy (SDT) and address the need to monitor therapeutic effects in vivo with a non-invasive approach. This rational design of organic sonosensitizer-based formulation shows great potential for clinical SDT against deep-seated cancer.

Self-Assembled Metal-Organic Nanoparticles for Multimodal Imaging-Guided Photothermal Therapy of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a high incidence of disease and the high recurrence rate is a major limitation for HCC treatment. To resolve such a challenge, multimodal imaging-guided photothermal therapy (PTT) provides a promising candidate for HCC treatment. Herein, we use a facile method to develop a novel self-assembled theranostic nanoparticle (NP) based on manganese irons (Mn2+) and indocyanine green (ICG) under the protection of poly(vinylpyrrolidone) (PVP). The fabricated NPs possess the properties of strong NIR optical absorbance, high photothermal conversion efficiency and multimodal imaging. Through intravenous injection, these NPs could highly accumulate in HepG2 tumor via the enhanced permeability and retention effect, as revealed by fluorescence/photoacoustic/magnetic resonance imaging, leading to an obviously improved in vivo therapeutic outcome. This study demonstrates that our self-assembled NPs could be a potential platform for multimodal imaging-guided PTT of HCC in future clinical therapy.

Gadolinium-Encapsulated Graphene Carbon Nanotheranostics for Imaging-Guided Photodynamic Therapy

Photosensitizers (PS) are an essential component of photodynamic therapy (PDT). Conventional PSs are often porphyrin derivatives, which are associated with high hydrophobicity, low quantum yield in aqueous solutions, and suboptimal tumor-to-normal-tissue (T/N) selectivity. There have been extensive efforts to load PSs into nanoparticle carriers to improve pharmacokinetics. The approach, however, is often limited by PS self-quenching, pre-mature release, and nanoparticle accumulation in the reticuloendothelial system organs. Herein, a novel, nanoparticle-based PS made of gadolinium-encapsulated graphene carbon nanoparticles (Gd@GCNs), which feature a high 1 O2 quantum yield, is reported. Meanwhile, Gd@GCNs afford strong fluorescence and high T1 relaxivity (16.0 × 10-3 m-1 s-1 , 7 T), making them an intrinsically dual-modal imaging probe. Having a size of approximately 5 nm, Gd@GCNs can accumulate in tumors through the enhanced permeability and retention effect. The unbound Gd@GCNs cause little toxicity because Gd is safely encapsulated within an inert carbon shell and because the particles are efficiently excreted from the host through renal clearance. Studies with rodent tumor models demonstrate the potential of the Gd@GCNs to mediate image-guided PDT for cancer treatment. Overall, the present study shows that Gd@GCNs possess unique physical, pharmaceutical, and toxicological properties and are an all-in-one nanotheranostic tool with substantial clinical translation potential.