Zipeng Zhen

Photostimulated near-infrared persistent luminescence as a new optical read-out from Cr3+-doped LiGa5O8

In conventional photostimulable storage phosphors, the optical information written by x-ray or ultraviolet irradiation is usually read out as a visible photostimulated luminescence (PSL) signal under the stimulation of a low-energy light with appropriate wavelength. Unlike the transient PSL, here we report a new optical read-out form, photostimulated persistent luminescence (PSPL) in the near-infrared (NIR), from a Cr3+-doped LiGa5O8 NIR persistent phosphor exhibiting a super-long NIR persistent luminescence of more than 1,000 h. An intense PSPL signal peaking at 716 nm can be repeatedly obtained in a period of more than 1,000 h when an ultraviolet-light (250–360 nm) pre-irradiated LiGa5O8:Cr3+ phosphor is repeatedly stimulated with a visible light or a NIR light. The LiGa5O8:Cr3+ phosphor has promising applications in optical information storage, night-vision surveillance, and in vivo bio-imaging.

RGD Modified Apoferritin Nanoparticles for Efficient Drug Delivery to Tumors

Ferritin (FRT) is a major iron storage protein found in humans and most living organisms. Each ferritin is composed of 24 subunits, which self-assemble to form a cage-like nanostructure. FRT nanocages can be genetically modified to present a peptide sequence on the surface. Recently, we demonstrated that Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (RGD4C)-modified ferritin can efficiently home to tumors through RGD-integrin αvβ3 interaction. Though promising, studies on evaluating surface modified ferritin nanocages as drug delivery vehicles have seldom been reported. Herein, we showed that after being precomplexed with Cu(II), doxorubicin can be loaded onto RGD modified apoferritin nanocages with high efficiency (up to 73.49 wt %). When studied on U87MG subcutaneous tumor models, these doxorubicin-loaded ferritin nanocages showed a longer circulation half-life, higher tumor uptake, better tumor growth inhibition, and less cardiotoxicity than free doxorubicin. Such a technology might be extended to load a broad range of therapeutics and holds great potential in clinical translation.

Hollow chitosan–silica nanospheres as pH-sensitive targeted delivery carriers in breast cancer therapy

Promising drug nanocarriers consisting of mono-dispersed and pH sensitive chitosan-silica hollow nanospheres (CS-SiO(2) HNPs) suitable for breast cancer therapy are produced and investigated. The SiO(2) HNPs are fabricated using a one-step, one-medium process which obviates the need for post-treatment to remove the templates, additional dissolution, or calcination. Taking advantage of the cross-linking reaction with (3-Glycidyloxypropyl) trimethoxysilane (GTPMS), cationic polysaccharide-chitosan decorates the surface and produces pH sensitive CS-SiO(2) HNPs. The materials enable controlled release of loaded drugs in pericellular and interstitial environments. In particular, the antibody molecule (to ErbB 2) can be conjugated onto the surface of the CS-SiO(2) HNPs thereby allowing the hollow nanospheres to serve as a targeted delivery agent to breast cancer cells. TNF-α are delivered to MCF-7 breast cancer cells under both in vitro and in vivo conditions to suppress the growth of cancerous cells and even kill them with high therapeutic efficacy. Owing to their hollow inner cavity and porous structures, the CS-SiO(2) HNPs are excellent pH-responsive targeted nanocarriers.

Ferritin Nanocages To Encapsulate and Deliver Photosensitizers for Efficient Photodynamic Therapy against Cancer

Photodynamic therapy is an emerging treatment modality that is under intensive preclinical and clinical investigations for many types of disease including cancer. Despite the promise, there is a lack of a reliable drug delivery vehicle that can transport photosensitizers (PSs) to tumors in a site-specific manner. Previous efforts have been focused on polymer- or liposome-based nanocarriers, which are usually associated with a suboptimal PS loading rate and a large particle size. We report herein that a RGD4C-modified ferritin (RFRT), a protein-based nanoparticle, can serve as a safe and efficient PS vehicle. Zinc hexadecafluorophthalocyanine (ZnF16Pc), a potent PS with a high (1)O2 quantum yield but poor water solubility, can be encapsulated into RFRTs with a loading rate as high as ~60 wt % (i.e., 1.5 mg of ZnF16Pc can be loaded on 1 mg of RFRTs), which far exceeds those reported previously. Despite the high loading, the ZnF16Pc-loaded RFRTs (P-RFRTs) show an overall particle size of 18.6 ± 2.6 nm, which is significantly smaller than other PS-nanocarrier conjugates. When tested on U87MG subcutaneous tumor models, P-RFRTs showed a high tumor accumulation rate (tumor-to-normal tissue ratio of 26.82 ± 4.07 at 24 h), a good tumor inhibition rate (83.64% on day 12), as well as minimal toxicity to the skin and other major organs. This technology can be extended to deliver other metal-containing PSs and holds great clinical translation potential.

Nanoscintillator-Mediated X-ray Inducible Photodynamic Therapy for In Vivo Cancer Treatment

Photodynamic therapy is a promising treatment method, but its applications are limited by the shallow penetration of visible light. Here, we report a novel X-ray inducible photodynamic therapy (X-PDT) approach that allows PDT to be regulated by X-rays. Upon X-ray irradiation, the integrated nanosystem, comprised of a core of a nanoscintillator and a mesoporous silica coating loaded with photosensitizers, converts X-ray photons to visible photons to activate the photosensitizers and cause efficient tumor shrinkage.

Tumor Vasculature Targeted Photodynamic Therapy for Enhanced Delivery of Nanoparticles

Delivery of nanoparticle drugs to tumors relies heavily on the enhanced permeability and retention (EPR) effect. While many consider the effect to be equally effective on all tumors, it varies drastically among the tumors’ origins, stages, and organs, owing much to differences in vessel leakiness. Suboptimal EPR effect represents a major problem in the translation of nanomedicine to the clinic. In the present study, we introduce a photodynamic therapy (PDT)-based EPR enhancement technology. The method uses RGD-modified ferritin (RFRT) as “smart” carriers that site-specifically deliver 1O2 to the tumor endothelium. The photodynamic stimulus can cause permeabilized tumor vessels that facilitate extravasation of nanoparticles at the sites. The method has proven to be safe, selective, and effective. Increased tumor uptake was observed with a wide range of nanoparticles by as much as 20.08-fold. It is expected that the methodology can find wide applications in the area of nanomedicine.

Development of Manganese-Based Nanoparticles as Contrast Probes for Magnetic Resonance Imaging

MRI is one of the most important imaging tools in clinics. It interrogates nuclei of atoms in a living subject, providing detailed delineation with high spatial and temporal resolutions. To compensate the innate low sensitivity, MRI contrast probes were developed and widely used. These are typically paramagnetic or superparamagnetic materials, functioning by reducing relaxation times of nearby protons. Previously, gadolinium(Gd)-based T1 contrast probes were dominantly used. However, it was found recently that their uses are occasionally associated with nephrogenic system fibrosis (NSF), which suggests a need of finding alternatives. Among the efforts, manganese-containing nanoparticles have attracted much attention. By careful engineering, manganese nanoparticles with comparable r1 relaxivities can be yielded. Moreover, other functionalities, be a targeting motif, a therapeutic agent or a second imaging component, can be loaded onto these nanoparticles, resulting in multifunctional nanoplatforms.

Gd-encapsulated carbonaceous dots with efficient renal clearance for magnetic resonance imaging.

Nanoprobes for MRI and optical imaging are demonstrated. Gd@C-dots possess strong fluorescence and can effectively enhance signals on T1 -weighted MR images. The nanoprobes have low toxicity, and, despite a relatively large size, can be efficiently excreted by renal clearance from the host after systemic injection.

Photostimulable near-infrared persistent luminescent nanoprobes for ultrasensitive and longitudinal deep-tissue bio-imaging.

In vivo fluorescence imaging suffers from suboptimal signal-to-noise ratio and shallow detection depth, which is caused by the strong tissue autofluorescence under constant external excitation and the scattering and absorption of short-wavelength light in tissues. Here we address these limitations by using a novel type of optical nanoprobes, photostimulable LiGa5O8:Cr3+ near-infrared (NIR) persistent luminescence nanoparticles, which, with very-long-lasting NIR persistent luminescence and unique photo-stimulated persistent luminescence (PSPL) capability, allow optical imaging to be performed in an excitation-free and hence, autofluorescence-free manner. LiGa5O8:Cr3+ nanoparticles pre-charged by ultraviolet light can be repeatedly (>20 times) stimulated in vivo, even in deep tissues, by short-illumination (~15 seconds) with a white light-emitting-diode flashlight, giving rise to multiple NIR PSPL that expands the tracking window from several hours to more than 10 days. Our studies reveal promising potential of these nanoprobes in cell tracking and tumor targeting, exhibiting exceptional sensitivity and penetration that far exceed those afforded by conventional fluorescence imaging.

Iron oxide nanoparticle encapsulated diatoms for magnetic delivery of small molecules to tumors.

Small molecules can be co-loaded with iron oxide nanoparticles onto diatoms. With an external magnetic field, the diatoms, after systemic administration, can be attracted to tumors. This study suggests a great potential of diatoms as a novel and powerful therapeutic vehicle.