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Title: Novel and multifunctional nanoplatforms for efficient synergistic cancer therapy and multimodal imaging
Authors: Fang, Xueyang
Degree: Ph.D.
Issue Date: 2022
Abstract: The rapid development of nanotechnology in the past decade provides an opportunity for advancing cancer treatment through a combination of in-depth understanding and utilization of fundamental concepts in different scientific aspects such as chemistry, engineering, and biomedicine. The advancement of technology helps to achieve highly efficient cancer diagnosis and treatment. The design and synthesis of functionalized nanomedicine rely on the distinguishing characteristics between normal and tumor tissue, which helps to improve the therapeutic efficacy by targeting and regulating the tumor microenvironment (TME). In chapter two, a novel cancer theranostic agent was designed and prepared for photoacoustic imaging (PAI)-guided chemo-photothermal synergistic therapy. Briefly, the novel theranostic agent was constructed with a gold nanocage (AuNC) core covered with selenium and chitosan (CS) shell. The theranostic agent encapsulated the anti-cancer drug doxorubicin (DOX) and acted as a multifunctional nanocomposite (AuNCs/DOX@Se-iRGD) with cancer targeting ability for enhancing cancer diagnosis and treatment. In vivo results indicated that the nanocomposite demonstrated a strong contrast-enhanced PAI signal 24 h after intravenous injection, which could provide contour and location information of the tumor. Furthermore, the combined treatment of chemo- and photothermal synergistic therapy significantly suppressed tumor growths, and showed negligible acute toxicity to major organs. This study provides a feasible strategy for constructing multifunctional nanoplatforms for future cancer therapy. The emergence of two-dimensional (2D) metal phosphorous trichalcogenides (MPX3) significantly broadens the applications of 2D materials. Yet, the rational design of MPX3-based composites and their specific applications in cancer theranostic biomedicine are rare. In chapter three, we reported the first design of a biomimetic FePSe3-based nanosheets (FePSe3@APP@CCM). The FePSe3-based nanosheets are loaded with anti-PD-1 peptide (APP) as inner component and coated with CT26 cancer cell membrane (CCM) as the outer shells, which served as a theranostic agent for multimodal imaging and cancer therapy. Under near-infrared (NIR) laser irradiation, the photothermal effects induced by these nanosheets not only directly abolished cancer cells but also triggered intense immune responses. Together with the APP, this single 2D nanoplatform could induce multiple immune responses, thus promoting the release of cytokines or presentation of antigens to activate cytotoxic T lymphocytes (CTLs) for efficient immunotherapeutic effects. Therefore, this study demonstrates the great potential of FePSe3@APP@CCM for future cancer theranostic.
In chapter four, we introduced iron and manganese into one MPX3 nanosystem for multifunctional application in the field of anticancer. Unlike the above-mentioned Fe-based nanosheets with a single metallic element, FMPS@PVP, combining iron and manganese, was able to catalyze H2O2 to produce O2 and generate cytotoxic ·OH simultaneously in the TME, and thus alleviating hypoxia and triggering chemo-dynamic therapy (CDT). Apart from the alleviation of hypoxia, FMPS@PVP could also inhibit the expression of hypoxia-inducible factor 1α (HIF-1α), which improved the function of CD4+ and CD8+ cells, thereby activating the proliferation and differentiation of CTLs with enhanced cytotoxicity for cancer cells. Moreover, FMPS@PVP could inhibit the expression of regulatory T cells (Tregs) and relieve the immunosuppressive effect of Tregs. Overall, this work broadens the application of the new MPX3 materials in the field of biomaterials for cancer therapy. In conclusion, findings in the three nanosystems could contribute to the research field of developing novel theranostic agents for cancer imaging and therapy.
Subjects: Nanomedicine
Cancer -- Diagnosis
Cancer -- Treatment
Hong Kong Polytechnic University -- Dissertations
Pages: 192 pages : color illustrations
Appears in Collections:Thesis

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