Shape memory micro-anchors with magnetic guidance for precision micro-vascular deployment.

Transcatheter medical micro-devices through circulatory system show great potential for therapy but lack strategies to stably anchor them at the desired site in vascularized tissues to take actions. Here a shape memory functionalized biodegradable magnetic micro-anchor (SM2A) is developed to achieve magnetic guided endovascular localization through precisely controlled shape transformation. The SM2A comprises anisotropic polylactide-based microparticle embedded with superparamagnetic Fe3O4 nanoparticles, exhibiting thermally activated tunable shape recovery modes at a body-friendly temperature range to accomplished an efficient endovascular anchoring effect in both decellularized liver organ and rabbit ear embolization models. The SM2A can be anchored at the target micro-vessel, exhibiting a controlled radial expansion of the vessel wall yielding with estimated stresses of 7-26 kPa in contact stress and 38-218 kPa in von Mises stress. The SM2A is a promising platform to incorporate diagnostic or therapeutic agents for precision deployment and in-situ action.

Visualization and Evaluation of Chemoembolization on a 3D Decellularized Organ Scaffold.

Transarterial chemoembolization (TACE) has emerged as the mainstay treatment for patients suffering from unresectable intermediate hepatocellular carcinoma and also holds the potential to treat other types of hypervascular cancers such as renal cell carcinoma. However, an in vitro model for evaluating both embolic performance and drug-release kinetics of the TACE embolic agents is still lacking since the current models greatly simplified the in vivo vascular systems as well as the extracellular matrices (ECM) in the organs. Here, we developed a decellularized organ model with preserved ECM and vasculatures as well as a translucent appearance to investigate chemoembolization performances of a clinically widely used embolic agent, i.e., a doxorubicin-loaded ethiodised oil (EO)-based emulsion. We, for the first time, utilized an ex vivo model to evaluate the liquid-based embolic agent in two organs, i.e., liver and kidneys. We found that the EO-based emulsion with enhanced stability by incorporating an emulsifier, i.e., hydrogenated castor oil-40 (HCO), showed an enhanced occlusion level and presented sustained drug release in the ex vivo liver model, suggesting an advantageous therapeutic effect for TACE treatment of hepatocellular carcinoma. In contrast, we observed that drug-release burst happened when applying the same therapy in the kidney model even with the HCO emulsifier, which may be explained by the presence of the specific renal vasculature and calyceal systems, indicating an unfavorable effect in the renal tumor treatment. Such an ex vivo model presents a promising template for chemoembolization evaluation before in vivo experiments for the development of novel embolic agents.

Decellularized liver as a translucent ex vivo model for vascular embolization evaluation.

Transarterial chemoembolization (TACE) is the preferred treatment for patients with unresectable intermediate stage hepatocellular carcinoma, however currently the development of embolic agents for TACE lacks in vitro models that closely represent the sophisticated features of the organ and the vascular systems therein. In this study, we presented a new strategy using an ex vivo liver model to provide a translucent template for evaluating embolic agents of TACE. The ex vivo liver model was developed through decellularizion of rat liver organs with preserved liver-specific vasculatures and improved transmittance of the whole liver up to 23% at 550 nm. Using this model, we investigated the embolization performances of both liquid and particle-based embolic agents, including penetration depth, embolization end-points, injection pressure and spatial distribution dynamics. We found that the embolization endpoint of liquid embolic agent such as ethiodised oil was strongly dependent on the injection pressure, and the pressure quickly built up when reaching the capillary endings, which could cause embolic agent leaking and potential tissue damages. In contrast, for particle-based embolic agents such as poly-dl-lactide microparticles and CalliSpheres® beads, their embolization endpoints were mainly determined by the particle size, whereas the particle densities close to the endpoints dramatically dropped down, which with the penetration depth represented two critical factors determining the embolic distribution. Such a decellularized organ model may open a new route to visually and quantitatively characterize embolization effects of various embolotherapies.

[Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus].

BACKGROUND & OBJECTIVE: H101 is an E1B-55 kDa gene-deleted replication-selective adenovirus, which showed a significant antitumor activity. This study was to compare effects and toxicities of intratumoral H101 injection combined with cisplatin plus 5-fluorouracil (PF) regimen or adriamycin plus 5-fluorouracil (AF) regimen versus PF or AF regimen alone in treating patients with head and neck or esophagus squamous cell cancer. METHODS: A total of 160 patients were recruited. PF regimen (cisplatin 20 mg/m(2) ivgtt, qd x 5d; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients have no history of PF chemotherapy,or sensitive to PF chemotherapy,while AF regimen (adriamycin 50 mg/m(2) iv,d1; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients didn't response to PF regimen. All patients were randomized to either receive intratumoral H101 injection (5.0 x 10(11)-1.5 x 10(12) VP/day for 5 consecutive days every 3 weeks) or not. Treatment repeated every 3 weeks,all patients have to receive at least 2 cycles of chemotherapy. RESULTS: Among 123 accordant patients,overall response rate of PF plus H101 group (group A1) was 78.8% (41/52),of PF alone group (group B1) was 39.6% (21/53),of AF plus H101 group (group A2) was 50.0% (7/14),of AF alone group (group B2) was 50.0% (2/4). Differences of response rates between group A1 and group B1,between group A1+A2 and group B1+B2 were significant (P=0.000). Main side effects were fever (45.7%), injection site reaction (28.3%),and influenza-like symptoms (9.8%). CONCLUSION: Intratumoral H101 injection showed a distinct efficacy in patients with squamous cell cancer of head and neck or esophagus,and was relatively safe.