Targeted reprogramming of tumor-associated macrophages for overcoming glioblastoma resistance to chemotherapy and immunotherapy.

The resistance of glioblastoma multiforme (GBM) to standard chemotherapy is primarily attributed to the existence of tumor-associated macrophages (TAMs) in the GBM microenvironment, particularly the anti-inflammatory M2 phenotype. Targeted modulation of M2-TAMs is emerging as a promising strategy to enhance chemotherapeutic efficacy. However, combination TAM-targeted therapy with chemotherapy faces substantial challenges, notably in terms of delivery efficiency and targeting specificity. In this study, we designed a pH-responsive hierarchical brain-targeting micelleplex loaded with temozolomide (TMZ) and resiquimod (R848) for combination chemo-immunotherapy against GBM. This delivery system, termed PCPA&PPM@TR, features a primary Angiopep-2 decoration on the outer layer via a pH-cleavable linker and a secondary mannose analogue (MAN) on the middle layer. This pH-responsive hierarchical targeting strategy enables effective BBB permeability while simultaneous GBM- and TAMs-targeting delivery. GBM-targeted delivery of TMZ induces alkylation and triggers an anti-GBM immune response. Concurrently, TAM-targeted delivery of R848 reprograms their phenotype from M2 to pro-inflammatory M1, thereby diminishing GBM resistance to TMZ and amplifying the immune response. In vivo studies demonstrated that targeted modulation of TAMs using PCPA&PPM@TR significantly enhanced anti-GBM efficacy. In summary, this study proposes a promising brain-targeting delivery system for the targeted modulation of TAMs to combat GBM.

Smartphone-Based Quantitative Detection of Ochratoxin A in Wheat via a Lateral Flow Assay.

Ochratoxin A (OTA) poses a severe health risk to livestock along the food chain. Moreover, according to the International Agency for Research on Cancer, it is also categorized as being possibly carcinogenic to humans. The lack of intelligent point-of-care test (POCT) methods restricts its early detection and prevention. This work establishes a smartphone-enabled point-of-care test for OTA detection via a fluorescent lateral flow assay within 6 min. By using a smartphone and portable reader, the assay allows for the recording and sharing of the detection results in a cloud database. This intelligent POCT provided (iPOCT) a linearity range of 0.1-3.0 ng/mL and a limit of detection (LOD) of 0.02 ng/mL (0.32 µg/kg in wheat). By spiking OTA in blank wheat samples, the recoveries were 89.1-120.4%, with a relative standard deviation (RSD) between 3.9-9.1%. The repeatability and reproducibility were 94.2-101.7% and 94.6-103.4%, respectively. This work provides a promising intelligent POCT method for food safety.