Ultradense Erythrocyte Bionic Layer Used to Capture Circulating Tumor Cells and Plasma-Assisted High-Purity Release.

The isolation and detection of rare circulating tumor cells (CTCs) from patient peripheral blood can help early diagnosis of cancer and evaluation of therapeutic outcomes. At present, most of the available strategies for enriching CTCs face serious problems with purity due to the nonspecific interactions between the capture medium and leukocytes. Inspired by the immune evasion ability of homologous red blood cells (RBCs), we modified the tumor-targeting molecule folic acid (FA) on the surface of RBCs by hydrophobic interactions. Under the treatment of polybrene, the charges on the surface of RBCs are neutralized, which reduces the mutual repulsion force. Furthermore, RBCs treated with polyethylene also have excellent deformability, thereby enabling engineered RBCs to form a dense bionic layer on the adhesive glass slide, which can greatly inhibit the nonspecific adhesion of leukocytes. The bionic layer can achieve high-purity enrichment of tumor cells in phosphate-buffered saline (PBS), and we can achieve high-activity release in plasma. The cell count showed over 80% capture efficiency and over 70% release rate, and the purity of CTCs obtained in the artificial blood sample after release was higher than 90%. The RBC bionic surface coating is notably cost-effective and highly applicable for CTC isolation in clinic practice, and thus provides new prospects for designing cell-material interfaces for advanced cell-based biomedical studies in the future.

Uricase and Horseradish Peroxidase Hybrid CaHPO4 Nanoflower Integrated with Transcutaneous Patches for Treatment of Hyperuricemia.

Currently, there are approximately 170 million hyperuricemia patients in China. Conventional drug therapy has limited clinical benefits and may induce serious side effects. Enzyme replacement therapy has attracted much attention owing to its advantages of strong specificity, small dosage, and remarkable curative effect. Uricase is an efficient oxidase, which can oxidize uric acid to allantoin and hydrogen peroxide, to reduce the uric acid level. In this study, we used a mild biomimetic method to prepare a novel uricase and horseradish peroxidase (HRP) loaded CaHPO4 nanoflower (uricase&HRP-CaHPO4 nanoflower). The nanoflower was then integrated with a hyaluronic acid dissolvable microneedle system (uricase&HRP-CaHPO4 @HA MN) to achieve transdermal drug delivery for the treatment of hyperuricemia, which has high patient compliance. In this system, the stability and catalytic activity of uricase could be improved by the CaHPO4 nanoflower, and HRP could decompose the hydrogen peroxide to accelerate the reaction of uricase. An in vivo study demonstrated that the uricase&HRP-CaHPO4 @HA MN could effectively reduce the uric acid level of blood as intravenous injection without side effects. Thus, this uricase&HRP-CaHPO4 @HA MN can facilitate transcutaneous hyperuricemia treatment and provide a new alternative for the exploration of clinical treatment of hyperuricemia.

Novel Approach of Using Near-Infrared Responsive PEGylated Gold Nanorod Coated Poly(l-lactide) Microneedles to Enhance the Antitumor Efficiency of Docetaxel-Loaded MPEG-PDLLA Micelles for Treating an A431 Tumor.

The combination of chemotherapy and photothermal therapy (PTT) plays a significant role in synergistic tumor therapy. However, a high dosage of chemotherapy drugs or photothermal agents may cause series side effects. To overcome these challenges, we designed a near-infrared (NIR) responsive PEGylated gold nanorod (GNR-PEG) coated poly(l-lactide) microneedle (PLLA MN) system (GNR-PEG@MN) to enhance antitumor efficiency of docetaxel-loaded MPEG-PDLLA (MPEG-PDLLA-DTX) micelles for treating an A431 tumor. The as-made GNR-PEG@MNs contained only 31.83 ± 1.22 µg of GNR-PEG per patch and exhibited excellent heating efficacy both in vitro and in vivo. Meanwhile, GNR-PEG@MN with the height of 480 µm had good skin insertion ability and was harmless to the skin. On the other hand, GNR-PEG@MN had good heating transfer ability in vivo, and the tumor sites could reach 50 °C within 5 min. In comparison with chemotherapy and PTT alone, the combination of low dosage MPEG-PDLLA-DTX micelles (5 mg/kg) and GNR-PEG@MNs completely eradicated the A431 tumor without recurrence in vivo, demonstrating a remarkable synergetic effect. Hence, GNR-PEG@MN could be a promising carrier to enhance the antitumor effect of MPEG-PDLLA-DTX micelles for treating superficial tumors and is expected to have a great potential in clinical translation for human epidermoid cancer therapy.

Visible-light-controllable drug release from multilayer-coated microneedles.

A method for the generation of visible-light-controllable drug release polyelectrolyte multilayers on poly(l-lactide) (PLLA) microneedles is developed by host-guest chemistry. In response to visible light irradiation, model drugs encapsulated on polyelectrolyte multilayers transfer into the skin following brief microneedle application.