Many studies have focused on developing effective therapeutic
strategies
to selectively destroy primary tumors, eliminate metastatic lesions,
and prevent tumor recurrence with minimal side effects on normal tissues.
In this work, we synthesized engineered cellular nanovesicles (ECNVs)
with tumor-homing and immune-reprogramming functions for photoacoustic
(PA) imaging-guided precision chemoimmunotherapy. M1-macrophage-derived
cellular nanovesicles (CNVs) were loaded with gold nanorods (GNRs),
gemcitabine (GEM), CpG ODN, and PD-L1 aptamer. The good histocompatibility
and tumor-homing effect of CNVs improved drug retention in the bloodstream
and led to their enrichment in tumor tissues. Furthermore, the photothermal
ability of GNRs enabled PA imaging-guided drug release. GEM induced
tumor immunogenic cell death (ICD), and CpG ODN promoted an immune
response to the antigens released by ICD, leading to long-term specific
antitumor immunity. In addition, the PD-L1 aptamer relieved the inhibitory
effect of the PD1/PD-L1 checkpoint on CD8+ T-cells and
augmented the immunotherapeutic effect. The synergistic innate and
adaptive immune responses enhanced the antitumor effect of ECNVs.
In summary, this nanoplatform integrates local targeted photothermal
therapy with extensive progressive chemotherapy and uses ICD to reshape
the immune microenvironment for tumor ablation.
Nowadays, the bipolar electrochemiluminescence (BP-ECL) is basically performed in complicated and expensive microfluidic devices, which may limit its wide applications. Here, a paper-based BP-ECL biosensor using "U"-shaped bipolar electrode (BPE) is developed for detection of oxidase-substrate biomarkers in human serum samples, with no need for complicated and expensive microfluidic technologies and peripheral apparatuses. The BP-ECL paper chips (PCs) can be well fabricated by two screen-printing processes: wax-screen-printing for on-paper hydrophilic and hydrophobic patterns, and carbon ink-screen-printing for BPEs and driving electrodes on wax-patterned paper. A low-cost and portable CCD is used to detect ECL signals from the luminol-H 2 O 2 reaction at the BPE anodic pole. Under optimized conditions, the paper-based BP-ECL biosensor can measure the concentrations of H 2 O 2 , with a linear range of 5-10000 μM and a detection limit of 0.424 μM. Importantly, the biosensor is capable of achieving a linear range of 10-5000 μM for choline, lactate or cholesterol; and the respectively corresponding detection limits are 0.573 μM, 3.132 μM and 7.418 μM. Moreover, it has an acceptable detection range, sensitivity, stability and selectivity. Finally, the developed method is successfully applied for determination of choline, lactate or cholesterol in human serum.
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