Biomedical Engineering Reference
In-Depth Information
spatial controllability and programmable pattern. The incorporation of
multifunctional components requires taking advantage of versatile linking
tools, such as the click reaction. Dong et al. prepared two-photon sensitive and
sugar-targeted nanocarriers from biodegradable amphiphiles.
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Both of the
linkages between the polymeric backbone and functional ligands depended on
click chemistry. More and more outstanding methodologies of integration are
emerging, such as degradable covalent bonds, reversible dynamic covalent
bonds, and noncovalent interactions.
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5.4 Applications in Drug and Gene Delivery
Various drugs and genes have been exploited to treat different malignancies.
Given that the side effects of these chemotherapeutic drugs are severe and the
exterior genes are rapidly degraded by various enzymes in the blood, delivery
vehicles such as polymeric micelles, vesicles, and conjugates should be adopted.
The common drugs contain doxorubicin, cisplatin, paclitaxel, methotrexate,
or 5-fluorouracil. Although the discovery of various antitumor drugs for
cancer therapy has made a giant leap, clinical outcomes are disappointing
because most of them exhibit severe side effects. Utilization of nanocarrier
systems like self-assembled polymeric micelles might overcome this problem.
The polymeric micelle carriers have several unique advantages, such as
enhancing the aqueous solubility and bioavailability of drugs, prolonging the
circulation time, improving the preferential accumulation at the tumor site by
the EPR effect, and reducing systemic side effects.
In the meantime, gene therapy has drawn significant attention over the past
decades as a potential method for treating genetic disorders and an alternative
approach to traditional chemotherapy applied in treating cancer. However,
free oligonucleotides and DNA are rapidly degraded by serum nucleases in the
blood when injected intravenously, so the design of effective vectors that
compact and protect oligonucleotides becomes indispensible for gene therapy.
The gene carriers mainly include two kinds, namely viral vectors and nonviral
vectors. For viral vectors, they are very efficient at transfection, but meanwhile
plagued by some downsides, such as immunogenicity, limitations in scale-up
procedures, and safety concerns. By comparison, nonviral vectors are endowed
with many advantages, like low/absent immunogenicity, easy manufacture,
high compound stability, and facile chemical modification, so nonviral gene
vectors are receiving more and more attention.
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5.4.1 Application as Drug Carriers
Owing to their outstanding pharmacokinetics and biodistribution profiles via
the EPR effect, drug delivery systems in the form of nanocarriers have
exhibited exciting efficacy for cancer treatments. Five drug-loaded patterns of
HBPs have been summarized.
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As shown in Figure 5.7, the drugs are tied to
HBPs through noncovalent interactions for the drug complexes (type 1) or
