Luru Dai

DNA Origami as an In Vivo Drug Delivery Vehicle for Cancer Therapy

Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and may have high levels of systemic toxicity due to their nonspecific distribution. Various materials have been explored to fabricate nanoparticles as drug carriers to improve delivery efficiency. However, most of these materials suffer from multiple drawbacks, such as limited biocompatibility and inability to engineer spatially addressable surfaces that can be utilized for multifunctional activity. Here, we demonstrate that DNA origami possessed enhanced tumor passive targeting and long-lasting properties at the tumor region. Particularly, the triangle-shaped DNA origami exhibits optimal tumor passive targeting accumulation. The delivery of the known anticancer drug doxorubicin into tumors by self-assembled DNA origami nanostructures was performed, and this approach showed prominent therapeutic efficacy in vivo. The DNA origami carriers were prepared through the self-assembly of M13mp18 phage DNA and hundreds of complementary DNA helper strands; the doxorubicin was subsequently noncovalently intercalated into these nanostructures. After conducting fluorescence imaging and safety evaluation, the doxorubicin-containing DNA origami exhibited remarkable antitumor efficacy without observable systemic toxicity in nude mice bearing orthotopic breast tumors labeled with green fluorescent protein. Our results demonstrated the potential of DNA origami nanostructures as innovative platforms for the efficient and safe drug delivery of cancer therapeutics in vivo.

Spatiotemporal Drug Release Visualized through a Drug Delivery System with Tunable Aggregation‐Induced Emission

Tetraphenylethene and doxorubicin are assembled into a self-indicating drug delivery system (TD NPs). TD NPs are decomposed into DOX and TPE NPs in lysosome. Since TD NPs, TPE NPs and DOX are all fluorescent, the detachment of DOX from TPE NPs is accompanied by fluorescence changing. By observing the fluorescence changes, the spatiotemporal drug release is visualized.

Self‐Propelled Janus Mesoporous Silica Nanomotors with Sub‐100 nm Diameters for Drug Encapsulation and Delivery

The synthesis of an innovative self-propelled Janus nanomotor with a diameter of about 75 nm that can be used as a drug carrier is described. The Janus nanomotor is based on mesoporous silica nanoparticles (MSNs) with chromium/platinum metallic caps and propelled by decomposing hydrogen peroxide to generate oxygen as a driving force with speeds up to 20.2 μm s(-1) (about 267 body lengths per second). The diffusion coefficient (D) of nanomotors with different H2 O2 concentrations is calculated by tracking the movement of individual particles recorded by means of a self-assembled fluorescence microscope and is significantly larger than free Brownian motion. The traction of a single Janus MSN nanomotor is estimated to be about 13.47×10(-15) N. Finally, intracellular localization and drug release in vitro shows that the amount of Janus MSN nanomotors entering the cells is more than MSNs with same culture time and particle concentrations, meanwhile anticancer drug doxorubicin hydrochloride loaded in Janus MSNs can be slowly released by biodegradation of lipid bilayers in cells.

Controlled Rod Nanostructured Assembly of Diphenylalanine and Their Optical Waveguide Properties

Diphenylalanine (FF) microrods were obtained by manipulating the fabrication conditions. Fourier transform infrared (FTIR), circular dichroism (CD), fluorescence (FL) spectroscopy, and X-ray diffraction (XRD) measurements revealed the molecular arrangement within the FF microrods, demonstrating similar secondary structure and molecular arrangement within FF microtubes and nanofibers. Accordingly, a possible mechanism was proposed, which may provide important guidance on the design and assembly manipulation of peptides and other biomolecules. Furthermore, characterization of a single FF microrod indicates that the FF microrod can act as an active optical waveguide material, allowing locally excited photoluminescence to propagate along the length of the microrod with coupling out at the microrod tips.

Near‐Infrared‐Activated Nanocalorifiers in Microcapsules: Vapor Bubble Generation for In Vivo Enhanced Cancer Therapy

Photothermal therapy based on gold nanostructures has been widely investigated as a state-of-the-art noninvasive therapy approach. Because single nanoparticles cannot harvest sufficient energy, self-assemblies of small plasmonic particles into large aggregates are required for enhanced photothermal performance. Self-assembled gold nanorods in lipid bilayer-modified microcapsules are shown to localize at tumor sites, generate vapor bubbles under near-infrared light exposure, and subsequently damage tumor tissues. The polyelectrolyte multilayer enables dense packing of gold nanorods during the assembly process, which leads to the formation of vapor bubbles around the excited capsules. The resulting vapor bubbles achieve a high efficiency of suppressing tumor growth compared to single gold nanorods. In vivo experiments demonstrated the ability of soft-polymer multilayer microcapsules to cross the biological barriers of the body and localize at target tissues.

Macrophage Cell Membrane Camouflaged Au Nanoshells for in Vivo Prolonged Circulation Life and Enhanced Cancer Photothermal Therapy

Macrophage cell membrane (MPCM)-camouflaged gold nanoshells (AuNS) that can serve as a new generation of photothermal conversion agents for in vivo photothermal cancer therapy are presented. They are constructed by the fusion of biocompatible AuNSs and MPCM vesicles. The resulting MPCM-coated AuNSs exhibited good colloidal stability and kept the original near-infrared (NIR) adsorption of AuNSs. Because AuNS carried high-density coverage of MPCMs, the totally functional portions of macrophage cells membrane were grafted onto the surface of AuNSs. This surface functionalization provided active targeting ability by recognizing tumor endothelium and thus improved tumoritropic accumulation compared to the red blood cell membrane-coating approach. These biomimetic nanoparticles significantly enhance in vivo blood circulation time and local accumulation at the tumor when administered systematically. Upon NIR laser irradiation, local heat generated by the MPCM-coated AuNS achieves high efficiency to suppress tumor growth and selectively ablate cancerous cells within the illuminated zone. Therefore, MPCM-coated AuNSs remained the natural properties of their source cells, which may improve the efficacy of photothermal therapy modulated by AuNSs and other noble-metal nanoparticles.

The rate of change in Ca2+ concentration controls sperm chemotaxis

Sperm navigate in a chemoattractant gradient by translating changes in intracellular calcium concentration over time into changes in curvature of the swimming path.

Macrophage Cell Membrane Camouflaged Mesoporous Silica Nanocapsules for In Vivo Cancer Therapy.

Engineering natural macrophage cell membrane-camouflaged mesoporous silica nanocapsules can reduce the arrested percentage of immune cells and tissues, effectively prolong the survival time of nanoparticles in blood circulation system, and improve the accumulation in tumor.

Visualization of the intracellular location and stability of DNA origami with a label-free fluorescent probe

We report a label-free fluorescent strategy to study the distribution and stability of DNA origami nanostructures in live, cellular systems, using carbazole-based biscyanine as a probe molecule which has the characteristic property of restriction of intramolecular rotation (RIR) induced emission.

Cell Membrane Tracker Based on Restriction of Intramolecular Rotation

The fluorescence of tetraphenylethylene (TPE), an archetypal luminogen, is induced by restriction of intramolecular rotation (RIR). TPE was grafted with palmitic acid (PA) onto a hydrophilic peptide to yield a cell membrane tracker named TR4. TR4 was incorporated into liposomes, where it showed significant RIR characteristics. When cells were incubated with TR4, cytoplasmic membranes were specifically labeled. TR4 shows excellent photostability and low cytotoxicity.