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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5919_Библиотеки_им_академика_М_И_Перельмана.pdf
Stimuli-Responsive Drug Delivery Systems: From Concept to Clinical Translation 139
Table 1
List of various pH-responsive materials
Stimulus Material Drug Reference
pH Liposome Antagomir-10b
Paclitaxel (PTX)
Chitosan hydrogels Antibiotics and anti-inflammatory
factors
Mesoporous bioglass with hydroxyapatite
(HAp)
Mesoporous ceramics with
hydroxyapatite
Metformin hydrochloride (MH) [8]
Levofloxacin (Levo) [10]
interaction between the solvent and the polymer, affects the temperature at which these transitions take place. The thermoresponsive behavior of polymers can be modified by introducing
reactants into the polymer/solvent system, including additives like
co-polymers, co-solvents, plasticizers, surfactants, and salts. These
additives can affect the quality of the solvent, thereby altering the
interactions between the solvent and the polymer [
4.3 Natural ThermoResponsive Materials
They include gelatin, agarose, and pectin. The most well-known
thermo-responsive natural polymer is gelatin. A possible delivery
method for bone formation from BMP9-transduced mesenchymal
stem cells is polydiolcitrate-gelatin scaffolds with thermosresponsive qualities [
12]. Poly(N-alkyl substituted acrylamide)
PNIPPAm nanofibers for release of doxorubicin were synthesized
using 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride and N-hydroxysuccinimide as crosslinking agents
13]. Additionally, gelatin nanoparticles were created for the drug
[
delivery of doxorubicin [
14]. Thermo-responsive chitosan/β-gly-
cerophosphate hydrogels were developed for the sustained delivery
of venlafaxine hydrochloride [
15].
[6, 7]
[9]
11].
4.4 Synthetic Thermo-Responsive Materials
They include PEG–PPG–PEG copolymer poly(N-vinyl-alkylamides), poly(N-alkyl substituted acrylamides), and PEG–PLLA/
PDLA–PEG copolymer, among many others. An extensively studied thermo-responsive polymers are based on PNIPAAm, a poly
(N-alkyl substituted acrylamide). Gene therapy, tissue engineering,
and drug delivery are just a few of the biomedical applications for
PNIPAAm-based polymers (e.g., thermo-responsive polyplex
micelles with PEG shells and PNIPAAm layers to protect DNA
cores for gene therapy) [
respond to temperature are provided in Table
16]. Key examples of materials that
2.
140 Manisha et al.
Table 2
List of various thermo-responsive materials
Stimulus Property Material Drug Reference
Temperature Synthetic Poly (N-alkyl substituted acrylamide)
PNIPPAm
PEG and PNIPPAm DNA [17]
Natural Chitosan (CS) and poly (ethylene glycol)-poly
(N-isopropylacrylamide) (PEGPNIPAAm)
Chitosan/β-glycerophosphate Venlafaxine
Biodegradable citrate-based, poly
(polyethyleneglycol citrate-co-Nisopropylacrylamide) mixed with gelatin
1-ethyl-3-(3-dimethyl-aminopropyl)-1-
and
(DPPE) (gelatin-co-
4.5 LightResponsive Materials
carbodiimide hydrochloride
N-hydroxysuccinimide
Nanopar
ticles based on gelatin, poly(lactide)
and 1,2-dipalmitoyl-sn-glycero-3phosphoethanolamine
PLA-DPPE)
Light is an exceptional stimulus for various applications due to its
controllable intensity and quick switching capability, wavelength,
and high spatial resolution [
UV to NIR, have been utilized for light-responsive materials.
Although UV light is widely used, its detrimental effects and shallow tissue penetration limit its applications. However, NIR light is
better suited for biomedical applications due to its deeper penetration and less toxicity to tissues [
temporal tunability, useful in therapeutics and dynamic cell culture
system [22]. Depending on the kind of photochemical reaction
occurring, light-responsive systems are classified into four categories [
23]: photocleavage (breaking of covalent bonds), photo-
thermal (dissipation of vibrational motion), photopolymerization
(in situ crosslinking), and photoisomerization (structural changes).
Photoisomerization is
visible light and is frequently used with azobenzenes [
spiropyrans [
25]. Photoexcitation of azobenzenes under UV light
(365 nm) causes a transition from the trans to the cis form, which is
utilized to destabilize dif ferent drug delivery vehicles such as dendrimers [
26], micelles [27], and liposomes [28]. The cis conforma-
tion disrupts the packing of these assemblies due to increased
polarity and steric effects. To extend the effects of light stimulation
and encourage the release of encapsulated drugs, a long cis lifetime
is desired. Research studies have demonstrated that the trans-cis
isomerization of an azobenzene derivative following its
Doxorubicin
(DOX)
Mesenchymal
stem cells
(MSCs)
hydrochloride
BMP9
(growth
differentiation
factor)
Doxorubicin
(DOX)
Doxorubicin
(DOX)
[16]
[18]
[15]
[12]
[13]
[14]
19, 20]. Different wavelengths, from
21]
hotoreactions offer spatio-
. P
a reversible process caused by UV and
24] and
Stimuli-Responsive Drug Delivery Systems: From Concept to Clinical Translation 141
incorporation into liposomes can result in bilayer defects and the
release of the entrapped payload [
29–31]. Azobenzene-glycolipids
incorporated into HSPC/DSPG/Chol liposomes have been shown
to control drug release by light stimuli [31], maintaining the drug’s
stability while it is entrapped and instantly releasing almost all of the
cargo when exposed to UV light. Furthermore, decyl-azobenzyltriethylammonium and cholesterol sulfate-based fluid-phase
photoresponsive nonphospholipid liposomes present a viable
method for regulating multidose release via photocycling between
the cis and trans azobenzene isomers [
nonphospholipid vesicles have
32]. These photoresponsive
advantages over traditional
phospholipid-based liposomes due to their distinct composition,
including improved chemical stability and increased
impermeability.
The ortho-nitrobenzyl (o-nitrobenzyl) moiety is the widely
used photocleavable molecule [
33]. One instance consists of drug
delivery micelles made of poly(S-(o-nitrobenzyl)-L-cysteine)-bpoly(ethylene glycol) block copolymers [34]. The o-nitrobenzyl
groups are gradually photocleaved upon exposure to light at wavelengths approximately 310 and 350 nm. This causes the selfassembled micelles to contract until they fully cleave, allowing the
controlled release of the encapsulated drug through adjustment of
the light exposure duration. This strategy is promising not only for
developing light-responsive polypeptide-based block co-polymers
but also for creating light-stimulated nanomedicine therapies. The
nitrobenzyl group has also been incorporated into liposomes for
drug delivery [
35–37].
Light
causes hydrolysis of o-nitrobenzyl
results in the separation of hydrophobic and hydrophilic groups
from the amphiphilic phospholipid, leading to destabilization of
membrane and drug release. By grafting an azide tail precursor
containing o-nitrobenzyl to an alkyne-functionalized lysolipid
through a copper-catalyzed azide–alkyne cycloaddition reaction,
liposomes possessing photocleavable characteristics can be generated in situ [
35]. Photolysis of the integrated o-nitrobenzyl group
changes the molecular structure of the photo-responsive phospholipid bilayer, increasing the phase transition and permeability of the
membrane, which disrupts the liposome structure and releases the
load. This in situ liposome production method creates photoresponsive liposomes for drug delivery by combining a click reaction with precursor design. Key examples of materials that respond
to light are provided in Table
3.
4.6 RedoxResponsive Polymeric
Materials
Redox-responsive polymers can respond to biological stimuli generated by oxidants or reductants found in the environment and can
also react to changes in redox conditions or the application of an
external voltage. Tetrathiafulvalene, viologens, organometallic
compounds, and disulfide bonds are important chemical groups
that contribute to their redox-responsive properties. These
142 Manisha et al.
Table 3
List of various light-responsive materials
Stimulus Material Drug Reference
Light Micelles of polyglycerol using spiropyran Hydrophobic
content
Liposomes formed by decyl-azobenzyl-triethylammonium and
cholesterol sulfate
Liposomes with multibranched gold nanoantennas [40]
The nitrobenzyl group incorporated into liposomes [35–37]
Poly(ethylene glycol) (PEG)-based hydrogel [11]
PEG and hyaluronic acid (HA) [41]
Polyesters hydrogels [42]
Polyacrylamide-based hydrogel with azobenzene Colloidal
gold encapsulated in liposomes
Hydrophobic
content
Mesenchymal
stem cells
[38, 39]
[31]
[43]
Table 4
List of various redox-responsive materials
Stimulus Material Drug Reference
Redox Carbon nanotube (CNT)-gelatin methacrylate (GelMA) [44]
Carbon nanotube (SWCNT) [45]
Poly(lactic acid) and barium titanate nanoparticles [46]
Glycolipid, chitosan, and stearic acid Doxorubicin
(DOX)
Polyethylene glycol and polycaprolactone Doxorubicin
(DOX)
Keratin grafted poly(N-(2-hydroxypropy l)
methacrylamide)
Polymers polyvinylidene fluoride (PVDF) [50]
Polypyrr
ole (PPy)
Doxor
ubicin
(DOX)
Interleukin IL-3 [51]
[47]
[48]
[49]
4.7 Magnetic Responsive Materials
materials are used in biomedical applications such as drug delivery
systems, specifically for cancer treatment, and the design of artificial
muscles and self-healing materials. Key examples of materials that
respond to redox condition are provided in Table
4.
Magnetic-responsive materials can be classified into four types:
oxides, coated oxides, metallic materials, and coated metallic materials [ 52].
The majority of the materials in the first group are iron
oxides, also known as ferrite nanoparticles, which are usually
arranged in crystalline forms like magnetite or maghemite. These
particles are either ferromagnetic or ferrimagnetic, but they resist
self-agglomeration when their sizes fall below 128 nm. Instead,
they behave like superparamagnetic particles. Particles smaller
than 50 nm are referred to as ultrasmall superparamagnetic iron
oxide nanoparticles (USPIONs) in this particular category, which is
Stimuli-Responsive Drug Delivery Systems: From Concept to Clinical Translation 143
called superparamagnetic iron oxide nanoparticles (SPIONs)
53]. Because ferrite particles have relatively inert surfaces,
[
coatings—typically with
silica—are frequently necessar y to increase
their reactivity. This uses organosilane molecules to perform multiple covalent modifications with various functional groups. Research
has demonstrated that silica-modified magnetite nanoparticles
(Fe3O4-MNPs) are produced by hydrolyzing tetraethyl orthosilicate (TEOS) and retain a similar spherical shape and distribution
unmodified MNPs. However
ration magnetization increases [
netic metallic
nanoparticles have a larger magnetic moment;
, as more silica is added, the net satu-
54–56]. Compared to oxides, mag-
to
however, they are more reactive to oxidizing agents and pyrophoric, meaning they can self-ignite above 55 °C, which makes
them challenging to work with [
52]. Their surfaces can be passi-
vated with protective layers using surfactants, polymers, precious
metals, or mild oxidation to lessen these problems [57].
Monodisperse magnetic nanoparticles with excellent stability
and shape-controllable sizes ranging from a few to tens of nanometers can be synthesized using top-down and bottom-up
approaches [
55, 58]. These methods are categorized into physical,
chemical, and biological techniques. Chemical methods, part of the
bottom-up approach, can be performed in both gas and wet phases.
The most commonly used and cited wet phase methods include
sol-gel processes, co-precipitation, hydrothermal synthesis, thermal
decomposition, microemulsion, sonolysis, solvothermal, and electrochemical techniques [
readily functionalized for a range of biological uses [
59]. Magnetic nanoparticles (MNPs) are
59–63]. An
important characteristic that biocompatible MNPs should have
been greater hydrophilicity, which will improve their water solubil-
57]. MNPs must first be stabilized in nonaqueous solvents
ity [
using a hydrocarbon layer prior to surface functionalization.
Then, techniques like ligand addition, ligand exchange, and hydrophilic silica coating can be used to achieve functionalization. To
make MNP more soluble in water, the ligand addition method
employs an amphiphilic molecule with both hydrophilic and hydrophobic groups [
64]. By forming a chemical bond with the surface, a
novel kind of coordinating group replaces the hydrocarbon layer
and adds a polar group that promotes water solubility in the ligand
exchange process. The most efficient way to achieve biocompatibility, stability, and hydrophilicity is the third technique, hydrophilic
silica coating, which is usually achieved using the sol-gel process,
which includes TEOS hydrolysis [
that respond to magnetic field are provided in Table
55]. Key examples of materials
5.
4.8 ElectroResponsive Materials
Electro-responsive delivery systems (ESDSs) can be synthesized
using drug carriers that align their dipoles when an electric potential is applied. According to the literature, conducting polymers
(ICPs) [
70] and hydrogel [71, 72] are promising and potentially
useful materials for these delivery systems.
144 Manisha et al.
Table 5
List of various magnetic responsive materials
Stimulus Material Reference
Magnetic MNPs with polysaccharide-based polymers [65]
Enzyme-MNP complex [66]
Iron oxide nanoparticles (USPION) [67]
Iron oxide MNPs [68]
Peptide-MNPs (magnetic nanoparticles) [69]
4.8.1 Intrinsically Conducting Polymers
In this case, a conducting polymer was created in the presence of
large immobilized anionic dopants, such as polystyrene sulfonate.
Electrostatic interactions can be utilized to incorporate the cationic
drug into the polymer backbone [
73]. One possible dopant to
incorporate uncharged drugs into the ICPs is anionic
β-cyclodextrin.
4.8.2 Hydrogels These gel networks are hydrophilic, meaning they can swell when a
lot of water is absorbed into their polymeric structure. Because of
their structure and hydrophilic nature, these macromolecular
three-dimensional networks have high concentrations of ionizable
groups within their polymer chains. While most electro-responsive
hydrogels used are polycations, polyanions have also been investigated. These hydrogels can undergo deswelling, swelling, and erosion in response to variations in electric potential.
4.9 EnzymeResponsive Materials
Phospholipids have attracted a lot of interest as carriers in enzymeresponsive drug delivery systems (DDS), along with polymeric and
inorganic nanomaterials. Enzyme-cleavable segments are present in
the main chains or side groups of these nanomaterials. For example,
nanoscale self-assembled materials are frequently combined with
linkers that can be recognized by an enzyme or modified by the
enzyme’s reaction product in order to design a drug delivery system
with spatial and temporal control [
74]. In inorganic nanosystems,
active targeting ligands that interact with particular enzymes are
used to impart enzyme sensitivity to nanoparticles [75, 76]. To
release the drug in enzyme-responsive drug delivery system, an
enzyme must change the structure or shape of the delivery vector.
Because of their ability to break bonds, enzymes such as oxidoreductases, phospholipases, and proteases—in particular, matrix
metalloproteinases (MMPs)—are frequently studied in DDS. Polymeric nanoparticles, liposomes, and inorganic nanoparticles like
gold and capped mesoporous silica nanoparticles are common vectors for enzyme-responsive drug delivery systems.
Another intriguing
platform for enzyme-responsive delivery
systems is gold nanoparticles (AuNPs). Researchers functionalized
the surface of AuNPs with a near-infrared fluorescence dye
Stimuli-Responsive Drug Delivery Systems: From Concept to Clinical Translation 145
5 Methods
connected by a peptide substrate to create an apoptosis imaging
probe [
77]. The fluorescence was quenched when the caspase-3
enzyme was not present. Nevertheless, the quenched fluorescence
was restored when caspase-3 cleaved the peptide substrate. In
biomedical applications, this imaging probe showed great promise
for apoptosis detection.
Over the past few decades, an excessive amount of research has
been conducted on stimuli-sensitive drug delivery systems (DDSs).
In this section, we will discuss the essential methods for designing
smart drug delivery systems (SDDS). These advanced systems are
designed to precisely regulate dose loading, ensure sustained
release, accommodate individual variability, and enhance targeted
permeability. SDDS exhibit dual or multi-responsiveness, responding to both internal and external stimuli for improved drug delivery
efficiency.
5.1 pH-Responsive Drug Delivery Systems
pH-responsive DDS for cancer therapy can be synthesized with
pH-cleavable bonds, such as acetal and hydrazone, added to the
carrier through linkers or cross-linkers containing these bonds.
Another method includes using ionic interactions for cross-linking
hydrogels. For instance, ionic interactions can be used to cross-link
polymeric precursors with basic or acidic groups, such as chitosan
and alginate, respectively. Because these carriers include functional
groups
that undergo protonation or deprotonation in response to
pH changes in the environment, they are susceptible to pH
changes. The ionic connections between polymer chains and the
ionic cross-linker are broken when an acidic pH is applied to a
hydrogel composed of acidic polymeric precursors because the
acidic functional groups get protonated. This causes the main
structure of the hydrogel to break down and the anticancer medications that are enclosed to leak out. Among the various mechanisms, the change in the swelling degree of the hydrogel network is
the most studied. To achieve this, the hydrogel network needs to
contain basic functional groups that can be protonated at low pH
levels, like those found in chitosan. Because of the electrostatic
repulsion forces between positively charged functional groups,
when these functional groups are protonated, osmotic pressure is
created within the hydrogel network, causing the hydrogel to
expand and change its degree of swelling. Furthermore, if the
polymer has both basic and acidic functional groups, such as carboxylic and amine groups, a change in pH will affect how much
these groups are protonated or deprotonated. Depending on the
pH level and the makeup of the polymeric precursors, this will
either cause the hydrogel network to expand or contract [
78].
146 Manisha et al.
5.2 RedoxResponsive Drug
Delivery Systems
5.3 ThermoResponsive Drug
Delivery Systems
To synthesize redox-responsive drug delivery systems (RSDSs),
disulfide bonds can be utilized as intermediate linkers within the
carrier structure. Incorporating a drug into the polymer chains via a
disulfide linker creates a redox-responsive delivery system. In biomedical applications, micelles synthesized from poly(ethylene glycol)-b-poly(caprolactone) (PEG-PCL) block co-polymer networks
have garnered significant attention for redox-responsive drug
release. An effective biodegradable micelle-based system using
PEG-SS-PCL block co-polymers has been synthesized for efficient
intracellular delivery of doxorubicin (DOX). This system works by
acting on the disulfide bonds between the polymeric blocks to
cause glutathione (GSH) to selectively detach the PEG block
from the carrier [
79]. Fur thermore, mesoporous silica nanoparti-
cles (MSNs) are popular material for creating nanocarriers in cancer
therapy because of their adjustable pore sizes, large surface area,
and excellent biocompatibility. For example, collagen-capped
MSNs have been used as redox-responsive nanocarriers to cleave
disulfide linkers and release fluorescein isothiocyanate under controlled conditions as a model drug [
80].
To synthesize thermo-responsive drug delivery systems (TSDSs),
an external temperature stimulus is necessary for targeted delivery
to tumor tissues. At a particular temperature, thermo-responsive
hydrogels experience a reversible phase transition that modifies
their hydrophobicity, solubility, and conformation [
81]. A variety
of tools, such as light, microwave radiation, and hot water perfusion, are used to raise the outside temperature. Nevertheless, the
penetration of these stimuli into thick tissues is limited [
82].
It has been shown that near-infrared (NIR) radiation is a useful
external stimulus for enhancing TSDS performance. NIR can target
tumor tissues specifically while causing the least amount of harm to
healthy tissue [
83]. A major obstacle in the development of TSDS is
choosing a hydrogel that can absorb and transform NIR energy
into heat [84]. Hydrophobic and hydrophilic segments are both
present in ideal TSDS hydrogels. Because poly(N-isopropyl acrylamide) (PNIPAM) has a lower critical solution temperature
(LCST) above 32 °C, it shows great promise for use in biomedical
applications [
85]. Strong hydrogen bonds between amide func-
tional groups and water molecules promote the dissolution of the
polymeric network below the LCST. These hydrogen bonds rupture when the ambient temperature approaches or surpasses the
LCST, which leads to the collapse of the polymer networks.
5.4 MagneticResponsive Drug
Delivery Systems
(MNPs)
MNPs can be created using various methods, including electrochemical approaches, microemulsion techniques, laser pyrolysis,
and solvothermal/hydrothermal methods [
86]. MNPs shows opti-
mal performance when their size is below 20 nm, at which point
they become superparamagnetic. Superparamagnetic nanoparticles
Stimuli-Responsive Drug Delivery Systems: From Concept to Clinical Translation 147
are composed of a biocompatible polymeric coating that can be
functionalized with drugs, antibodies, proteins, or plasmids, and a
core composed of magnetic materials, particularly iron oxides
87]. Polymers such as polyvinyl alcohol (PVA), poly
[
(N-isopropylamide) (PNIPAM), and polyethylene glycol (PEG)
are applied to the surfaces of iron oxide nanoparticles because of
their tendency to aggregate due to their hydrophobic nature. The
spleen or the mononuclear phagocyte system (MPS) can readily
eliminate large nanoparticles [
cles have zero
magnetization in the absence of a magnetic field,
86]. Superparamagnetic nanoparti-
which leads to high dispersion and inhibits aggregation and MPS
recognition [
88, 89].
A popular approach in the creation of magnetically responsive
nanocarriers is to coat MNPs with thermos-responsive polymers
such as PNIPAM and poloxamers. Through intramolecular interactions, the organic shell of these polymers holds drugs within its
branches; heat from an alternating magnetic field (AMF) causes the
polymer layer to collapse, freeing the trapped cargo. For example,
thermos-responsive polymers have been used to create mesoporous
silica nanoparticles [
90]. The silica matrix was filled with iron oxide
nanoparticles (IONPs), and the cargo was held in place by the silica
mesopores.
herm
A t
ostable polymeric shell consisting of N-isopropyl acrylamide (NIPAM) and N-(hydroxymethyl) acrylamide (NHMA) in a
90:10 ratio was applied to the drug-loaded magnetic nanoparticles.
This polymer transitions from linear to globular at 42–43 °C, which
is in the range of hyperthermia. When exposed to AMF, poly
(NIPAM/NHMA) can hold a significant number of therapeutic
agents inside the mesoporous silica matrix and release them. By
increasing the amount of PEO (the hydrophilic block), poloxamers,
which are poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers, can have their
transition temperature adjusted between 19 and 100 °C. Chen
et al. created magnetic, thermo-responsive, vitamin B12-loaded
micelles using poloxamers [
88]. Magnetically responsive nanocar-
riers (MNPs) are coated with biopolymers to improve their biocompatibility. Alginate hydrogel submicron beads were prepared by
incorporating silica-coated MNPs using alginate, a naturally occurring polymer obtained from brown algae [
91]. In a recent study,
MNPs and antibiotics were embedded in polyethylene glycol
dimethacrylate-cross-linked chitosan microbeads, enabling the
release of antibiotics with tunable kinetics based on the cross-linker
length, field strength, and frequency [
Elastin-like polypeptides
(ELPs) are one type of polypeptide
that has temperature-responsive characteristics [
92]
.
93]. ELPs are com-
posed of recurrent pentapeptide sequences, Val-Pro-Gly-X-Gly,
where the polymer’s transition temperature is influenced by the
hydrophilic nature of X (any amino acid). Another biopolymer
148 Manisha et al.
with a double helix that reacts to temperature is DNA. The four
nucleotides that make up each DNA strand are adenine (A), cytosine (C), thymine (T), and guanine (G). The double helix, which
splits at temperatures above the melting point, is formed by the
Watson-Crick bonds connecting the A-T and G-C bases. Based on
clusters of DNA-functionalized MNPs, Baglioni et al. created a
controlled DNA release system [
94].
An additional natural polymer called liposomes has been utilized to coat MNPs. To regulate the release of doxorubicin in
tumor cells, for instance, magnetic liposomes functionalized with
folate receptors were employed [
95]. Another tactic is to directly
bind therapeutic agents to MNP surfaces via temperatureresponsive linkers. Medication molecules can be attached to
MNPs through cycloaddition reactions, especially copper-catalyzed
azide-alkyne cycloaddition, which releases the molecules when
exposed to AMF. Using temperature-responsive linkers, the last
tactic entails directly attaching medicinal spices to the surface of
magnetic nanoparticles (MNPs). Cyclodextrins, especially
thermos-reversible ones, are now widely used to functionalize
MNPs. Drug molecules can be attached to MNPs using one such
reaction, the azide-alkyne cycloaddition catalyzed by copper. An
alternating magnetic field (AMF) can cause the drug molecules to
be released from the nanoparticles [
96].
5.5 LightResponsive Drug
Delivery System
One approach to designing a light-responsive DDS involves breaking covalent bonds between nanoparticles and drug molecules
using light. The photocleavable functional groups o-nitrobenzyl,
pyrene, and coumarin have been studied the most. These moieties
exhibit unique light-responsive properties and can shift the absorption maximum to absorb light, primarily UV-vis irradiation, by
utilizing substituent effects [
97]. For example, coumarin-
functionalized block copolymers have been used to create a
UV-triggered biocompatible micellar DDS [98]. By using atom
transfer radical polymerization to copolymerize coumarin methacrylate and n-butyl methacrylate, this system was produced. Then, in
the presence of light with a wavelength greater than 310 nm, the
anticancer medication 5-fluorouracil was covalently bound to the
coumarin. When UV light was applied at 245 nm, the medication
was gradually released into the cancer cells.
ferent approach to creating light-responsive DDS is to
A dif
modify the chemical structure. In these systems, noncovalent structural alterations like trans-to-cis transformations and polarity shifts
brought on by low-energy photons release cargo molecules that are
noncovalently bonded to nanocarriers when exposed to nearinfrared (NIR) radiation. When trans-to-cis transformation occurs,
light induces a conformational change in the double bond within
nanocarriers, thereby improving payload release. Azobenzene and
its derivatives, which undergo reversible photoisomerization with