Over the past few decades, colorimetric paper-based lateral
flow
immunoassay (LFIA) has emerged as a versatile analytical tool for
rapid point-of-care detection of infectious diseases with high simplicity
and flexibility. The LFIA sensitivity is based on color visualization
of the antibody-labeled nanoparticles bound with the target analytes
at the test line. Therefore, the nanoparticle design is crucial for
LFIA sensitivity. The traditional LFIA is based on spherical gold
nanoparticles, which usually suffer from poor sensitivity because
of very low optical contrast at the test line. To improve the LFIA
sensitivity, we have developed an LFIA based on gold nanostars (GNSs)
with different branch lengths and sharpness (GNS-1, GNS-2, and GNS-3),
which possess higher optical contrast than conventional gold nanospheres
(GNSPs). We have selected the bacterium Yersinia pestis as a model analyte system. The effective affinity of GNSPs and GNSs
with the Y. pestis fraction 1 (F1)
protein was quantitively investigated by colorimetric and optical
density measurements of the test line. The results show that GNS-3,
which has maximum spike length and branch sharpness, exhibits the
highest analytical sensitivity based on the limit of detection of
the LFIA readout compared to other GNSs and GNSPs. The detection limit
of the Y. pestis F1 antigen was achieved
up to 0.1 ng/mL for GNS-3, which is 100 times lower than that for
the GNSP at a 1 pmol/L concentration and 10 times lower than that
for the reported procedure based on traditional gold nanoparticles.
Overall, our prototype LFIA platform based on a highly spiked GNS
(GNS-3) exhibits high analytical sensitivity, indicating it to be
a promising candidate for routine LFIA application to detect infectious
diseases.
Bladder cancer has been ranked as one of the most commonly occurring cancers in men and women with approximately half of the diagnoses being the late stage and/or metastatic diseases. We have developed a novel cancer treatment by combining gold nanostar-mediated photothermal therapy with checkpoint inhibitor immunotherapy to treat bladder cancer. Experiment results with a murine animal model demonstrated that our developed photoimmunotherapy therapy is more efficacious than any individual studied treatment. In addition, we used intravital optical imaging with a dorsal skinfold window chamber animal model to study immune responses and immune cell accumulation in a distant tumor following our photoimmunotherapy. The mice used have the CX3CR1-GFP receptor on monocytes, natural killer cells, and dendritic cells allowing us to dynamically track their presence by fluorescence imaging. Our proof-of-principle study results showed that the photoimmunotherapy triggered anti-cancer immune responses to generate anti-cancer immune cells which accumulate in metastatic tumors. Our study results illustrate that intravital optical imaging is an efficient and versatile tool to investigate immune responses and mechanisms of photoimmunotherapy in future studies.
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