is suggested that chitosan also plays the role of crosslinker as well as serving as a
surfactant. Further, an increase in LCST due to the presence of iron oxide MNPs is a
very important result and it can be said that dipole–dipole interactions might prevent
the collapse of crosslinked polymer segments.
The inclination of the researchers during the last two decades towards the development and implementation of new environmentally responsive smart materials,
biomimetics, biosensors, artificial muscles, DDSs, and chemical separations to
name a few has given tremendous importance to nanogels instead of bulk hydrogels
[216]. Hydrogel transitions, i.e., volume changes that occur in response to changing
environmental conditions such as temperature, pH, ionic strength, solvent composition, electric stimuli, and γ-radiation have been studied. Therefore, the nanogels can
be designed to undergo large changes in their chemical, mechanical, optical, and
electrical make-up in response to a chemical stimulus, biomolecular interaction, or
electromagnetic field. Natural biopolymers have been widely used to prepare responsive hydrogels for biomedical application due to their biocompatibility, low toxicity,
and a high content of functional groups [217–222]. Although significant benefits have
been achieved, few studies have yet been conducted on preparation of natural
biopolymer-based bionanomaterials for simultaneous sensing, imaging diagnosis,
and therapy. One study describes a multifunctional system on the basis of immobilization of quantum dots (QDs) into the hydroxypropyl cellulose-polyacrylic acid
(HPC-PAA) semi-interpenetrating (semi-IPN) nanogel for simultaneous optical
pH-sensing, tumor cell imaging, and pH-regulated delivery of anticancer drugs
[223]. Despite the exciting conception, several key issues remain unaddressed in
this system. To address the key issues, Wu et al. [224] further reported the development of a new class of chitosan-based responsive hybrid nanogels (R h < 100 nm)
with CdSe QDs (3.2–3.8 nm) in-situ immobilized in chitosan–poly(methacrylic acid)
(chitosan–PMMA) semi-IPN networks for integration of optical pH-sensing, tumor
cell imaging, and controlled drug delivery. The mean diameter of chitosan–PMAA
nanogels varies from 174.5 to 74.7 nm when the MAA:chitosan ratio changes from
2.10 to 0.53. These hybrid nanogels exhibited marked swelling at both high and low
pH values, but a minimum size at pH 5.0–5.5. The swelling of the hybrid nanogels
containing pH-responsive groups is governed by the internal osmotic pressure due to
the mobile counter-ions contained within the particles, which balance the internal
electrostatic repulsion. At high pH values (e.g., >8.0), the nanogels remained nearly
at a maximum swelling degree due to the high degree of ionization of the –COO
À
groups of the PMMA chains. With a decrease in pH, the –COO
À groups gradually
protonate to –COOH, which not only enhance the hydrogen bonding interactions
between the chitosan and PMMA chains, but also reduce the Coulombic repulsion
within the particles, resulting in a gradual decrease in the size of hybrid nanogels. It is
worth mentioning that the fluorescence of the hybrid nanogels does not completely
quench, even at extreme pH environments; thus, the hybrid nanogels can be used for
cell labeling under physiologically important pH conditions.
Engineering of Polysaccharides via Nanotechnology
119
surfactant. Further, an increase in LCST due to the presence of iron oxide MNPs is a
very important result and it can be said that dipole–dipole interactions might prevent
the collapse of crosslinked polymer segments.
The inclination of the researchers during the last two decades towards the development and implementation of new environmentally responsive smart materials,
biomimetics, biosensors, artificial muscles, DDSs, and chemical separations to
name a few has given tremendous importance to nanogels instead of bulk hydrogels
[216]. Hydrogel transitions, i.e., volume changes that occur in response to changing
environmental conditions such as temperature, pH, ionic strength, solvent composition, electric stimuli, and γ-radiation have been studied. Therefore, the nanogels can
be designed to undergo large changes in their chemical, mechanical, optical, and
electrical make-up in response to a chemical stimulus, biomolecular interaction, or
electromagnetic field. Natural biopolymers have been widely used to prepare responsive hydrogels for biomedical application due to their biocompatibility, low toxicity,
and a high content of functional groups [217–222]. Although significant benefits have
been achieved, few studies have yet been conducted on preparation of natural
biopolymer-based bionanomaterials for simultaneous sensing, imaging diagnosis,
and therapy. One study describes a multifunctional system on the basis of immobilization of quantum dots (QDs) into the hydroxypropyl cellulose-polyacrylic acid
(HPC-PAA) semi-interpenetrating (semi-IPN) nanogel for simultaneous optical
pH-sensing, tumor cell imaging, and pH-regulated delivery of anticancer drugs
[223]. Despite the exciting conception, several key issues remain unaddressed in
this system. To address the key issues, Wu et al. [224] further reported the development of a new class of chitosan-based responsive hybrid nanogels (R h < 100 nm)
with CdSe QDs (3.2–3.8 nm) in-situ immobilized in chitosan–poly(methacrylic acid)
(chitosan–PMMA) semi-IPN networks for integration of optical pH-sensing, tumor
cell imaging, and controlled drug delivery. The mean diameter of chitosan–PMAA
nanogels varies from 174.5 to 74.7 nm when the MAA:chitosan ratio changes from
2.10 to 0.53. These hybrid nanogels exhibited marked swelling at both high and low
pH values, but a minimum size at pH 5.0–5.5. The swelling of the hybrid nanogels
containing pH-responsive groups is governed by the internal osmotic pressure due to
the mobile counter-ions contained within the particles, which balance the internal
electrostatic repulsion. At high pH values (e.g., >8.0), the nanogels remained nearly
at a maximum swelling degree due to the high degree of ionization of the –COO
À
groups of the PMMA chains. With a decrease in pH, the –COO
À groups gradually
protonate to –COOH, which not only enhance the hydrogen bonding interactions
between the chitosan and PMMA chains, but also reduce the Coulombic repulsion
within the particles, resulting in a gradual decrease in the size of hybrid nanogels. It is
worth mentioning that the fluorescence of the hybrid nanogels does not completely
quench, even at extreme pH environments; thus, the hybrid nanogels can be used for
cell labeling under physiologically important pH conditions.
Engineering of Polysaccharides via Nanotechnology
119