Microbubble Biointerfacing by Regulation of the Platelet Membrane Surfactant Activity at the Gas-Liquid Interface for Acute Thrombosis Targeting.

Biointerfacing nanomaterials with cell membranes has been successful in the functionalization of nanoparticles or nanovesicles, but microbubble functionalization remains challenging due to the unique conformation of the lipid monolayer structure at the gas-liquid interface that provides insufficient surfactant activity. Here, we describe a strategy to rationally regulate the surfactant activity of platelet membrane vesicles by adjusting the ratio of proteins to lipids through fusion with synthetic phospholipids (i.e., liposomes). A "platesome" with the optimized protein-to-lipid ratio can be assembled at the gas-liquid interface in the same manner as pulmonary surfactants to stabilize a microsized gas bubble. Platesome microbubbles (PMBs) inherited 61.4 % of the platelet membrane vesicle proteins and maintained the active conformation of integrin αIIbß3 without the talin 1 for fibrin binding. We demonstrated that the PMBs had good stability, long circulation, and superior functionality both in vitro and in vivo. Moreover, by molecular ultrasound imaging, the PMBs provide up to 11.8 dB of ultrasound signal-to-noise ratio enhancement for discriminating between acute and chronic thrombi. This surface tension regulating strategy may provide a paradigm for biointerfacing microbubbles with cell membranes, offering a potential new approach for the construction of molecular ultrasound contrast agents for the diagnosis of different diseases.

Engineering Platelets with PDL1 Antibodies and Iron Oxide Nanoparticles for Postsurgical Cancer Immunotherapy.

Recently, immune checkpoint blockade (ICB) therapy has achieved great success in inhibition of the recurrence and metastasis of tumor. However, this therapy is challenged by the poor delivery efficiency of ICB agents and the insufficient activation of antitumor immunity by ICB only. Here, we describe a strategy using platelets as carriers for co-delivery of ICB agents (anti-PDL1 antibodies, aPDL1) and photothermal agents (iron oxide nanoparticles, IONPs) to the postsurgical tumor site, which simultaneously provides photothermal therapy for ablation of residual tumor cells and ICB therapy for blocking the immunoinhibitory signals in the tumor microenvironment. We engineered platelets by chemical conjugation of aPDL1 and physical adsorption of IONPs on the surfaces of the platelets. Once they were adhered to the subendothelium of the surgical site, engineered platelets (P-P-IO) were activated and released aPDL1 and IONPs to the surrounding tissue. Upon laser irradiation, mild photothermal therapy (PTT) induces necrosis of residual tumor cells, producing tumor-associated antigens to generate innate immune responses. The co-delivered aPDL1 leads to efficient antitumor immunity, as evidenced by the reduced recurrence of the residual tumor and improved infiltration of both CD4+ and CD8+ T cells in a postsurgical breast tumor xenograft mouse model. We believe our strategy holds great promise in the clinic for combating postsurgical cancer recurrence.

A nanoparticle-containing polycaprolactone implant for combating post-resection breast cancer recurrence.

The recurrence and metastasis of tumor after surgery is the main cause of death for patients with breast cancer. Systemic chemotherapy suffered from low delivery efficiency to tumors and the side effects of chemo drugs. Localized chemotherapy using drug-containing implants is an alternative, while the reconstruction of breast tissue is generally considered after chemotherapy, resulting in a second surgery for patients. Here, we describe a strategy using implantable drug-containing polymeric scaffolds to deliver chemo drugs directly to the post-resection site, and simultaneously provide mechanical support and regenerative niche for breast tissue reconstruction. When doxorubicin was loaded in mesoporous silica nanoparticles and subsequently incorporated into polycaprolactone scaffolds (DMSN@PCL), a 9-week sustained drug release was achieved post implantation in mice. The local recurrence of residual tumor after surgery was significantly inhibited within 4 weeks in a post-surgical mouse model bearing xenograft MDA-MB-231 tumor. DMSN@PCL scaffolds exhibited good biocompatibility in mice during the treatment. We believe our strategy holds great promise as an adjuvant localized chemotherapy in clinics for combating post-resection breast cancer recurrence.

Diagnostic value of conventional ultrasound and shear wave elastography in detecting transjugular intrahepatic portosystemic shunt dysfunction.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) dysfunction can cause recurrent portal hypertension (PH)-related complications such as ascites and gastroesophageal variceal bleeding. Portography is invasive and costly limits its use as a screening modality. PURPOSE: To assess the clinical value of conventional ultrasound in combination with point shear wave elastography (pSWE) to predict TIPS dysfunction. MATERIAL AND METHODS: A total of 184 patients with cirrhosis scheduled for TIPS implantation were enrolled in this study and evaluated retrospectively. The splenoportal venous blood flow parameter, liver stiffness (LS), and spleen stiffness (SPS) were measured. Outcome measures included differences in portal vein velocity (PVV), splenic vein velocity (SPVV), LS, and SPS. The accuracy of change in PVV (ΔPVV), SPVV (ΔSPVV), and SPS (ΔSPS) to diagnose TIPS dysfunction was investigated. RESULTS: TIPS dysfunction occurred in 28 of 184 patients (15.2%). Eighteen (64.3%) patients had shunt stenoses and 10 (35.7%) had shunt occlusion. Portal vein diameter (PVD), PVV, splenic vein diameter (SPVD), SPVV, LS, and SPS were not significantly different between the TIPS normal and TIPS dysfunction groups. Compared with the TIPS normal group, PVV and SPVV of the TIPS dysfunction group decreased significantly, whereas SPS increased significantly (P < 0.001). The values of areas under the receiver operating characteristic curves of ΔPVV, ΔSPVV, and ΔSPS for the diagnosis of TIPS dysfunction were 0.97, 0.96, and 0.87, respectively. CONCLUSION: pSWE showed a diagnostic efficacy comparable to conventional ultrasound for diagnosing TIPS dysfunction and can be used routinely after TIPS procedures.