Author: Fan, Yadi
Title: Red emissive carbon dots-based nanocomposites for multimodality imaging-guided synergistic phototherapy
Advisors: Yang, Mo (BME)
Degree: Ph.D.
Year: 2021
Subject: Nanostructured materials
Cancer -- Photochemotherapy
Hong Kong Polytechnic University -- Dissertations
Department: Department of Biomedical Engineering
Pages: xii, 126 pages : color illustrations
Language: English
Abstract: Over the past decades, multi-functional nanocomposites that combine diagnosis and therapy into one platform have become an attractive way for cancer therapy. Carbon dots (CDs), as a class of zero-dimensional (0D) nanomaterial, have presented advantages in various fields (e.g., biosensing, bioimaging, delivery, and cancer theranostics) owing to its superior optical properties, biocompatibility, and easy modification. However, most of the reported CDs are blue emissive, which could be affected by the disturbance of auto-fluorescence, light scattering from tissue with low tissue penetration depth. In contrast, red-emitting CDs can decrease auto-fluorescence as well as the damage to the cells. It is also possible to integrate red-emitting CDs with other nanomaterials to generate hybrid nanocomposite for multi-modality imaging. Multi-modality imaging with complementary advantages is needed to overcome the limitations of simple or dual mode imaging to provide more information in anatomy and physiology. Moreover, red-emitting CDs have strong absorption in the near-infrared region (NIR) with photothermal (PTT) and photodynamic (PDT) effects, which show great potential in cancer phototherapy. Due to the limitation and unsatisfying efficacy of traditional methods such as surgery, radiotherapy etc., the NIR light triggered non-invasive phototherapy provide the promising for more effective cancer therapy. In this thesis, we developed two red-emissive CDs based hybrid nanocomposite for multi-modality imaging-guided synergistic phototherapy.
In the first part of this thesis, we chelated gadolinium (Gd) metal ions into red CDs with various doping rates using a microwave-assisted synthesis approach for fluorescence/photoacoustic/magnetic resonance imaging (FL/PA/MRI) guided PDT/PTT cancer therapy. The red CDs have superior NIR absorption to overcome the limitations of auto-fluorescence disturbance and light scattering of short wavelength. The doped Gd has excellent T1-weighted relaxivity for MRI imaging. The optimized Gd doping rate (Gd 1%) was selected to achieve good red fluorescence, PA and MRI imaging signals at the same time. Moreover, Gd-CDs also showed good photothermal conversion efficiency as well as photodynamic effects under NIR irradiation. The combined PDT/PTT therapeutic efficacy of the obtained nanocomposite (Gd-CDs) to suppress tumor growth under NIR irradiation was confirmed both in vitro and in vivo.
Since most tumor sites are characterized by hypoxia, this promotes tumor progression and metastasis, and also limits the therapeutic effects related to oxygen. To overcome this problem, our second hybrid nanocomposite (AIPH@MSN/CDs-MnO2-PEG) was synthesized based on its smart response to tumor microenvironment (TME) for co-enhanced synergistic PDT/PTT therapy. Here, red fluorescence CDs were used as the photosensitisers for PDT, photothermal agent for PTT, as well as for PA and FL imaging. AIPH (2, 2'-Azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride) encapsulated by carrier of mesoporous silicon (MSN) could respond to the local hyperthermia and generate free radicals as oxygen-independent PDT. Manganese dioxide (MnO2) was responsive to endogenous H2O2 in acidic TME to produce oxygen in situ for overcoming tumor hypoxia to promote the oxygen-dependent PDT. Therefore, a largely enhanced synergistic PTT/PDT cancer therapy effect was achieved. Moreover, the simultaneous degradation of MnO2 enhanced T1-weighted MRI relaxation through water-soluble Mn ions as well as generated ultrasound signals due to the generation of O2 bubbles. The co-enhanced PDT combined with PTT under single NIR laser irradiation were demonstrated both in vitro and in vivo. Under the guidance of FL/MRI/US/PA multi-modality imaging, the nanocomposite exhibited excellent biocompatibility and synergistic anti-tumor performance.
Rights: All rights reserved
Access: open access

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