Nanotechnology for anticancer applications
Item statusRestricted Access
Embargo end date17/07/2024
Cancer is one of the most deadly diseases in the world. Except for surgery, chemotherapy and radiation therapy are the main methods for cancer treatment currently. Nanoparticle (NP) based drug delivery systems have been introduced as suitable vehicles to deliver conventional drug formulations to tumour sites precisely. However, the NPs platforms still face complex biological obstacles in the clinic that severely limit their therapeutic outcomes. The ineffective intratumoral penetration is one of the significant reasons that nano-drug formulations cannot cure cancer completely. At present, a series of studies demonstrated that the delivery of nanomedicines is highly affected by their physical and chemical properties. In addition, magnetophoresis is a promising strategy to improve the tumor penetration of nanomedicines by gaining the help of external magnetic propulsive force. Therefore, the penetration of ultrasmall iron oxide (Fe3O4) NPs with various sizes (10, 15 and 21 nm), shapes (spherical and octahedral), surface charges (negative and positive) and magnetizations in a 3D tumor spheroid model was determined in chapter 2. The results demonstrate that relatively large (21 nm), spherical, and positively charged ultrasmall Fe3O4 NPs showed greater penetration in tumor under a magnetic field. Furthermore, in chapter 3, the thesis combined ultrasmall Fe3O4 NPs and anticancer drugs to design novel and facile magnetic self-assembled drug NPs to improve tumor penetration ability and loading efficiency of clinical drugs. The results prove that the strategy can be used for various drugs. After the formation of the magnetic doxorubicin (DOX) NPs, glycol chitosan (GC) was applied to modify the surface to enable the NPs’ acidity-responsiveness. These Fe3O4-DOX@GC NPs can be effectively directed by external magnetic fields and transform to a positive charge in the tumour microenvironment, dramatically raising cell internalization and tumor penetration. Recently, the strategy of carrier-free nanomedicines based on the selfassembly of therapeutic molecules has been proposed to achieve an extremely high drug loading capacity (> 80%) and higher anticancer efficiency of chemotherapeutic drugs. This thesis further explores the possibility of carrier-free nanomedicines in terms of synergistic therapy rather than simple chemotherapy in chapter 4. A carrierfree drug NP, which combines a chemotherapeutic drug, curcumin (Cur), and a phototherapeutic drug, indocyanine green (ICG), was developed for synergistic cancer treatment (ICG-Cur NPs). Subsequently, ICG-Cur NPs were modified with metalphenolic networks (MPNs) to allow them to escape from the degradative endo/lysosomal environment during the cellular uptake process. The results show that the thick MPN coating could facilitate the fast endo/lysosomal escape of ICG-Cur NPs within 4 h, leading to remarkably enhanced anticancer efficiency in 3D solid tumor models. Real-time obtaining information on the drug release situation and structural integrity of nanomedicines is crucial to the drug delivery system in body application. In chapter 5, a self-assembled FRET drug NP with the function of self-monitored drug release and dissociation was developed. The achievement of this self-monitored function is based on the FRET and J-aggregate phenomena between a fluorescent anticancer drug, Cur (acts as a donor) and a fluorescent dye, DiI (acts as an acceptor). The prepared FRET NPs showed a strong red shift of fluorescence spectra (FRET Jband) beyond the FRET emission wavelength. The results show a direct correlation between the drug content in NPs and the relative intensity of NPs at the FRET J-band. Consequently, this work provides a new design strategy for carrier-free drug NPs in terms of the convenient self-monitor of drug release and NP degradation, and this design has a high potential to be applied to other drugs. At present, there are many types of anticancer drugs on the market, and each may possess different physicochemical and pharmacological properties. The purposes of chapter 6 are to find out whether the performance and success of nanomedicines are more relevant to the properties of loaded drugs. This work performed a meta-analysis to compare nanomedicines based on three frequently used clinical anticancer drugs, including DOX, paclitaxel (PTX) and docetaxel (Doce), in terms of their pharmacokinetics, tumor accumulation and therapeutic efficiencies relative to free drugs. Collectively, the results suggest that the performance of nanomedicines is corporately determined by the type of loaded drugs and the type of nanocarriers. These findings are expected to guide nanomedicines scientists when designing nanomedicines based on different drugs and considering which drug to be loaded on nanomedicines.