|Noninvasive diagnosis and treatment of in situ early-stage cancers assisted by biomimetic nanoplatforms
|Lai, Puxiang (BME)
|Cancer -- Imaging
Magnetic particle imaging
Hong Kong Polytechnic University -- Dissertations
|Department of Biomedical Engineering
|xxii, 112 pages : color illustrations
|Cancer claims nearly 10 million lives each year and is the second leading cause of death worldwide. Increasing the rate of early diagnosis could considerably increase the 5-year survival rate from 26% to 91%. At present, the ultimate standard for clinical diagnosis of cancer is the pathological section, which depends on the localization and preliminary judgment of imaging diagnosis, and usually reflects advanced stages of development. It is clinically impactful if the changes in the tumor microenvironment and biological organization in the early stage of cancer can be sensed and identified. That said, these microenvironment changes are subtle and difficult to be accurately identified with existing imaging techniques. Therefore, early, stable, and reliable imaging modalities play a crucial role in cancer diagnosis and therapy. In recent years, innovative imaging methods have been explored to achieve higher sensitivity, specificity, and accuracy, improving the state of the art for early diagnosis and therapy-efficacy detection of tumors.
In this thesis, to achieve early theranostic of tumors, we explored the application of two new imaging methods, photoacoustic imaging (PAI) and magnetic particle imaging (MPI), combined with functional optimization of imaging contrast agents. Aiming at the challenges of poor targeting ability, immune rejection, and poor biocompatibility of contrast agents, a set of strategies of cell membrane modification were proposed to enhance the imaging performance.
Firstly, we utilized PAI that combines the advantages of optical imaging and ultrasound imaging to achieve deep-tissue (liver) penetration and high-contrast imaging. The abundant sinusoids in the liver provides a strong background photoacoustic (PA) signal, and the liver, the main organ of the immune system, traps many nanoprobes in order to remove foreign substances, greatly reducing the signal-to-noise ratio (SNR). Therefore, we proposed to use the erythrocyte membrane to modify gold nano-stars to prolong the circulation time of the nanoprobes in vivo to enhance the enrichment of the nanoprobes in tumors. Owing to the immune-escaping property from the erythrocyte membrane, we successfully verified that the functionalized gold nano-stars can assist PAI to detect small tumors up to 2 mm in diameter in the liver, demonstrating the biomimetic nanoplatforms are phenomenal in cancer theranostic.
However, the accumulating effect of nanoprobes in brain glioma imaging is still unsatisfactory due to the presence of the blood-brain barrier (BBB), which impedes the delivery of theranostic agents to the tumor site. Therefore, to improve the BBB penetration and active targeting properties of the nanoprobes, homologous tumor cell membranes were extracted and coated with magnetic nanoparticles (MNPs). In this thesis, we demonstrated depth-independent and highly sensitive MPI as well as its usage as a precise and quantitative imaging method, as its signal comes directly from the magnetic moment of MNP with no background signal interference.
In the first two works, we demonstrated the promising performance of the biomimetic NPS for early diagnosis of cancers. Moreover, their safety in in-vivo and non-invasive photothermal therapy could also be achieved. In the experiments, the heterogeneity of tumors and individual differences among patients will lead to differences in treatment efficacies, and new drug delivery methods were hence explored in this thesis. In addition to assessing the efficacy by studying the recovery from cancer, it is desirable to visualize the delivery of drugs during treatment process. Therefore, in the third study, we used PAI to monitor drug delivery in real time, providing valuable information on the distribution and concentration of the drugs in the tumor. This information can be used to optimize the therapeutic strategy and improve the treatment outcomes for patients with cancer.
Collectively, the three studies discussed in this thesis highlight the emerging bio-imaging modalities and the versatility and effectiveness of biomimetic nanoplatforms in liver cancer and glioblastoma, providing new opportunities for early cancer diagnosis and therapy.
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