86
mosensitive polymers that exhibit sol-gel transitions in response to
both endogenous and exogenous thermal fluctuations [6], and (iii)
redox-sensitive polymers commonly containing labile disulfide
linkages that respond to endogenous redox alterations [7]. Other
emerging types of responsive polymers for targeted drug delivery
have also been reported and can be separated based on the origin
of stimuli. For internally triggered DDS, biologically, enzyme- and
inflammation-responsive polymers have been developed while
externally triggered DDS include polymers that are photo, ultrasound, magnetically, or electrically sensitive [8]. Recent trends in
polymer DDS account for the combination of two or more of the
aforementioned characteristics in one polymeric structure which
can result in a dual or multisensitive polymer, thus leading to a
multifunctional material that can act in a more holistic approach
for treatment of the targeted disease [9]. The morphology of these
kinds of polymers at the nanoscale can result in various moieties
like polymersomes, nanocontainers, hydrogels, polymeric micelles,
nanospheres, and dendritic nanocarriers [10].
The use of stimuli-responsive polymers as DDS is based on
their ability to interact with a drug, bind covalently or electrostatically, and release it upon specific trigger, which depends on the
type of the targeted disease [11]. For example, in cancer theranostics the rationale behind the design of a responsive polymeric
nanomaterial is based on the physiology of cancer tissues, acidic
environment, thermal liability (40–45 °C), redox instabilities,
specificity of growth factors, and rise of the enhanced permeation
and retention (EPR) effect [12]. Bearing this into consideration by
loading an anticancer drug in a single- or multisensitive polymeric
nanocarrier which is further functionalized with targeting agents
for cancer cells, prolonged circulation of the drug, selective recognition, and targeted release of the drug can be achieved. In this
way chemotherapy becomes more efficient and less toxic for the
patient [13]. Toniolo et al. synthesized a triple-sensitive (pH,
thermo, redox) polymeric nanocontainer, loaded with the model
anticancer drug daunorubicin hydrochloride. These nanocarriers
exhibited a drug-loading capacity and an encapsulation efficiency
of 85% and 68% approximately whereas the drug release profile was
significantly enhanced at acidic pH, increased temperature, and
presence of glutathione [14].
Inorganic nanomaterials can also be incorporated in the structure of polymeric nanocarriers. For the purpose of this study, iron
oxide nanoparticles are presented. Iron oxide nanoparticles are
superparamagnetic (mNPs) and thus under the application of an
alternating magnetic field they dissipate thermal energy due to
Néel and Brown relaxations. One of the most studied applications
of mNPs in cancer treatment is through magnetic hyperthermia
treatment [15]. Polymeric nanocontainers containing iron oxide
nanoparticles (mNCs) can be used in magnetic hyperthermia and
cause a synergistic effect of temperature increase in the tumor area
Maria Theodosiou et al.
mosensitive polymers that exhibit sol-gel transitions in response to
both endogenous and exogenous thermal fluctuations [6], and (iii)
redox-sensitive polymers commonly containing labile disulfide
linkages that respond to endogenous redox alterations [7]. Other
emerging types of responsive polymers for targeted drug delivery
have also been reported and can be separated based on the origin
of stimuli. For internally triggered DDS, biologically, enzyme- and
inflammation-responsive polymers have been developed while
externally triggered DDS include polymers that are photo, ultrasound, magnetically, or electrically sensitive [8]. Recent trends in
polymer DDS account for the combination of two or more of the
aforementioned characteristics in one polymeric structure which
can result in a dual or multisensitive polymer, thus leading to a
multifunctional material that can act in a more holistic approach
for treatment of the targeted disease [9]. The morphology of these
kinds of polymers at the nanoscale can result in various moieties
like polymersomes, nanocontainers, hydrogels, polymeric micelles,
nanospheres, and dendritic nanocarriers [10].
The use of stimuli-responsive polymers as DDS is based on
their ability to interact with a drug, bind covalently or electrostatically, and release it upon specific trigger, which depends on the
type of the targeted disease [11]. For example, in cancer theranostics the rationale behind the design of a responsive polymeric
nanomaterial is based on the physiology of cancer tissues, acidic
environment, thermal liability (40–45 °C), redox instabilities,
specificity of growth factors, and rise of the enhanced permeation
and retention (EPR) effect [12]. Bearing this into consideration by
loading an anticancer drug in a single- or multisensitive polymeric
nanocarrier which is further functionalized with targeting agents
for cancer cells, prolonged circulation of the drug, selective recognition, and targeted release of the drug can be achieved. In this
way chemotherapy becomes more efficient and less toxic for the
patient [13]. Toniolo et al. synthesized a triple-sensitive (pH,
thermo, redox) polymeric nanocontainer, loaded with the model
anticancer drug daunorubicin hydrochloride. These nanocarriers
exhibited a drug-loading capacity and an encapsulation efficiency
of 85% and 68% approximately whereas the drug release profile was
significantly enhanced at acidic pH, increased temperature, and
presence of glutathione [14].
Inorganic nanomaterials can also be incorporated in the structure of polymeric nanocarriers. For the purpose of this study, iron
oxide nanoparticles are presented. Iron oxide nanoparticles are
superparamagnetic (mNPs) and thus under the application of an
alternating magnetic field they dissipate thermal energy due to
Néel and Brown relaxations. One of the most studied applications
of mNPs in cancer treatment is through magnetic hyperthermia
treatment [15]. Polymeric nanocontainers containing iron oxide
nanoparticles (mNCs) can be used in magnetic hyperthermia and
cause a synergistic effect of temperature increase in the tumor area
Maria Theodosiou et al.