An extravascular fluid transport system based on structural framework of fibrous connective tissues in human body.

OBJECTIVE: Interstitial fluid in extracellular matrices may not be totally fixed but partially flow through long-distance oriented fibrous connective tissues via physical mechanisms. We hypothesized there is a long-distance interstitial fluid transport network beyond vascular circulations. MATERIALS AND METHODS: We first used 20 volunteers to determine hypodermic entrant points to visualize long-distance extravascular pathway by MRI. We then investigated the extravascular pathways initiating from the point of thumb in cadavers by chest compressor. The distributions and structures of long-distance pathways from extremity ending to associated visceral structures were identified. RESULTS: Using fluorescent tracer, the pathways from right thumb to right atrium wall near chest were visualized in seven of 10 subjects. The cutaneous pathways were found in dermic, hypodermic and fascial tissues of hand and forearm. The perivascular pathways were along the veins of arm, axillary sheath, superior vena cava and into the superficial tissues on right atrium. Histological and micro-CT data showed these pathways were neither blood nor lymphatic vessels but long-distance oriented fibrous matrices, which contained the longitudinally assembled micro-scale fibres consistently from thumb to superficial tissues on right atrium. CONCLUSIONS: These data revealed the structural framework of the fibrous extracellular matrices in oriented fibrous connective tissues was of the long-distance assembled fibres throughout human body. Along fibres, interstitial fluid can systemically transport by certain driving-transfer mechanisms beyond vascular circulations.

Magnetic Mesoporous Silica Nanoparticles Cloaked by Red Blood Cell Membranes: Applications in Cancer Therapy.

Targeted drug delivery is an emerging technological strategy that enables nanoparticle systems to be responsive for tumor therapy. Magnetic mesoporous silica nanoparticles (MMSNs) were cloaked with red blood cell membrane (RBC). This integrates long circulation, photosensitizer delivery, and magnetic targeting for cancer therapy. In vivo experiments demonstrate that RBC@MMSNs can avoid immune clearance and achieve magnetic field (MF)-induced high accumulation in a tumor. When light irradiation is applied, singlet oxygen rapidly generates from hypocrellin B (HB)-loaded RBC@MMSN and leads to the necrosis of tumor tissue. Such a RBC-cloaked magnetic nanocarrier effectively integrates immunological adjuvant, photosensitizer delivery, MF-assisted targeting photodynamic therapy, which provides an innovative strategy for cancer therapy.

DNA origami/gold nanorod hybrid nanostructures for the circumvention of drug resistance.

We herein demonstrate that DNA origami can work as a multifunctional platform integrating a chemotherapeutic drug (doxorubicin), gold nanorods and a tumour-specific aptamer MUC-1, to realize the effective circumvention of drug resistance. Doxorubicin (DOX) was loaded efficiently onto DNA origami through base pair intercalation and surface-modified gold nanorods (AuNRs) were assembled onto the DNA origami through DNA hybridization. Due to the active targeting effect of the assembled aptamers, the multifunctional nanostructures achieved increased cellular internalization of DOX and AuNRs. Upon near-infrared (NIR) laser irradiation, the P-glycoprotein (multidrug resistance pump) expression of multidrug resistant MCF-7 (MCF-7/ADR) cells was down-regulated, achieving the synergistically chemotherapeutic (DOX) and photothermal (AuNRs) effects.

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.

A Self-Assembled DNA Origami-Gold Nanorod Complex for Cancer Theranostics.

A self-assembled DNA origami (DO)-gold nanorod (GNR) complex, which is a dual-functional nanotheranostics constructed by decorating GNRs onto the surface of DNA origami, is demonstrated. After 24 h incubation of two structured DO-GNR complexes with human MCF7 breast cancer cells, significant enhancement of cell uptake is achieved compared to bare GNRs by two-photon luminescence imaging. Particularly, the triangle shaped DO-GNR complex exhibits optimal cellular accumulation. Compared to GNRs, improved photothermolysis against tumor cells is accomplished for the triangle DO-GNR complex by two-photon laser or NIR laser irradiation. Moreover, the DO-GNR complex exhibits enhanced antitumor efficacy compared with bare GNRs in nude mice bearing breast tumor xenografts. The results demonstrate that the DO-GNR complex can achieve optimal two-photon cell imaging and photothermal effect, suggesting a promising candidate for cancer diagnosis and therapy both in vitro and in vivo.

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.

Selective inhibition of breast cancer stem cells by gold nanorods mediated plasmonic hyperthermia.

Cancer stem cells (CSCs) have been identified in a variety of cancers and emerged as a new target for cancer therapy. CSCs are resistant to many current cancer treatments, including chemotherapy and radiation therapy. Therefore, eradication of this cell population is a primary objective in cancer therapy. Here, we report gold nanorods (AuNRs) mediated photothermal treatment can selectively eliminate CSCs in MCF-7 breast cancer cells. It significantly reduced the aldehyde dehydrogenase positive (ALDH(+)) cells subpopulation and the mammosphere formation ability of treated cells. Also, the gene expression of stem cell markers was decreased. Cellular uptake assay revealed that polyelectrolyte conjugated AuNRs could be internalized by CSCs much more and faster than non cancer stem cells (NCSCs), which might be the main reason for the selective elimination of CSCs. We further loaded salinomycin (SA), a CSCs inhibitor with polyelectrolyte conjugated AuNRs to get a synergistic CSCs inhibition. Enhanced inhibition of CSCs was obtained by NIR light triggered drug release and hyperthermia. This CSCs-targeted thermo-chemotherapy platform provides a new combinatorial strategy for efficient inhibition of CSCs, which is promising to improve cancer treatment and may overcome the chemoresistance and recurrence of cancer.