Nanotechnology for anticancer applications
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Date
17/07/2023Item status
Restricted AccessEmbargo end date
17/07/2024Author
Feng, Xue
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Abstract
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.