Search Results (58)

Skin cancer is the world’s fifth most diagnosed malignancy and is increasingly occurring in young adults. The elevated morbidity and mortality of skin cancer are known to be highly correlated with its frequent recurrence after tumor excision. Although regimens such as chemotherapy and/or immunotherapy are often administered following surgical treatments, the patients may suffer from severe side effects, drug resistance, and/or high cost during treatments, indicating that the development of an effective and safe modality for skin cancer after surgery is still highly demanded nowadays. In this study, an injectable and thermoresponsive hyaluronic acid/hexamethylene diisocyanate-Pluronic F127 block copolymer crosslinking composite hydrogel loaded with indocyanine green (ICG) and camptothecin (CPT), called ICHHPG, was developed for photochemotherapy of skin cancer after surgery. ICHHPG can be self-gelationed at 37 °C and stabilizes ICG in the gel matrix. Upon NIR exposure, ICHHPG can generate hyperthermia and consequently provide photothermal therapy when the ICG dosage is >5 μM. Furthermore, ICHHPG may provide a remarkably enhanced cancericidal effect compared to the equal concentration of free ICG (≤10 μM) or CPT (≤1000 μM) alone, and more than 95% of cancer cells can be destroyed as the intra-gel doses of ICG/CPT were elevated to 10/800 μM. Given the confirmed cytotoxicity together with its fluidic and thermoresponsive characteristics which are foreseeably favorable for wound coverage, the developed ICHHPG is highly applicable for use in skin cancer treatment after surgical excision. Full article

This study investigates the effects of homopolymer additives and kinetic traps on the self-assembly of poly(ethylene glycol)-b-poly(lactide) (PEG-PLA) block copolymer (BCP) nanostructures in aqueous environments. By using non-adsorbing PEG homopolymers to kinetically trap PEG-PLA nanostructures, we demonstrate that varying the concentration and molecular weight of the added PEG induces a reversible micelle-to-vesicle transition. This transition is primarily driven by changes in the molecular geometry of the PEG-PLA BCPs due to excluded volume screening effects. Additionally, the reversible vesicle-to-micelle transition upon PEG’s removal shows time and temperature dependency, highlighting the influence of the system’s kinetic nature. Intermediate structures observed during the transition support a mechanism based on shifts in the molecular geometry of PEG-PLA. As a proof of concept, we show that PEG-PLA vesicles can act as thermoresponsive delivery systems, retaining dye at low temperatures (4 °C) and releasing it upon heating (37 °C). Overall, this work presents a novel approach to controlling BCP nanostructures’ morphology, with implications for drug delivery and material science applications. Full article

A series of copolymers containing a thermo-responsive biocompatible first block of poly[di(ethylene glycol) methyl ether methacrylate)-co-(oligo(ethylene glycol) methyl ether methacrylate], P(DEGMA-co-OEGMA) were chain-extended to incorporate either poly(N-isopropylacrylamide), PNIPAAm or poly(N-isopropylacrylamide-co-butyl acrylate), P(NIPAAm-co-BA) as second thermo-responsive block using reversible addition–fragmentation chain transfer (RAFT) polymerization. P(DEGMA-co-OEGMA)-b-PNIPAAm copolymers showed two response temperatures at 33 and 43 °C in an aqueous solution forming stable aggregates at 37 °C. In contrast, P(DEGMA-co-OEGMA)-b-P(NIPAAm-co-BA) copolymers showed aggregation below room temperature due to the shift in response temperature provoked by the presence of hydrophobic butyl acrylate (BA) units, and shrinkage upon heating up to body temperature, while maintaining the second response temperature above 40 °C. The terminal trithiocarbonate group of the block copolymers was modified to a thiol functionality and used to stabilize gold nanorods (GNRDs) via the “grafting to” approach. The Localized Surface Plasmon Resonance (LSPR) absorption band of GNRDs with an aspect ratio of 3.9 (length/diameter) was located at 820 nm after surface grafting with block copolymers showing a hydrodynamic diameter of 160 nm at 37 °C. On the other hand, the stability of the P(DEGMA-co-OEGMA)-b-PNIPAAm@GNRDs and P(DEGMA-co-OEGMA)-b-P(NIPAAm-co-BA)@GNRDs nanohybrids was monitored for 8 days; where the LSPR absorption band did not shift or show any broadening. Aqueous dispersed nanohybrids were irradiated with a near-infrared laser (300 mW), where the temperature of the surroundings increased 16 °C after 16 min, where conditions for no precipitation were determined. These tailored temperature-responsive nanohybrids represent interesting candidates to develop drug nanocarriers for photo-thermal therapies. Full article

In this work, we present basic research on developing thermogel carriers containing high amounts of model antibody immunoglobulin G (IgG) with potential use as injectable molecules. The quantities of IgG loaded into the gel were varied to evaluate the possibility of tuning the dose release. The gel materials were based on blends of thermoresponsive and degradable ABA-type block copolymers composed of poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA–PEG–PLGA) or poly(lactide-co-caprolactone)-b-poly(ethylene glycol)-b-(lactide-co-caprolactone) (PLCL–PEG–PLCL). Primarily, the gels with various amounts of IgG were obtained via thermogelation, where the only factor inducing gel formation was the change in temperature. Next, to control the gels’ mechanical properties, degradation rate, and the extent of antibody release, we have tested two approaches. The first one involved the synergistic physical and chemical crosslinking of the copolymers. To achieve this, the hydroxyl groups located at the ends of the PLGA–PEG–PLGA chain were modified into acrylate groups. In this case, the thermogelation was accompanied by chemical crosslinking through the Michael addition reaction. Such an approach increased the dynamic mechanical properties of the gels and simultaneously prolonged their decomposition time. An alternative solution was to suspend crosslinked PEG–polyester nanoparticles loaded with IgG in a PLGA–PEG–PLGA gelling copolymer. We observed that loading IgG into thermogels lowered the gelation temperature (T_GEL) value and increased the storage modulus of the gels, as compared with gels without IgG. The prepared gel materials were able to release the IgG from 8 up to 80 days, depending on the gel formulation and on the amount of loaded IgG. The results revealed that additional, chemical crosslinking of the thermogels and also suspension of particles in the polymer matrix substantially extended the duration of IgG release. With proper matching of the gel composition, environmental conditions, and the type and amount of active substances, antibody-containing thermogels can serve as effective IgG delivery materials. Full article

Aqueous solutions of a thermoresponsive diblock copolymer poly(di-[ethylene glycol] methyl ether methacrylate)-b-poly(2-[diisopropylamino] ethyl methacrylate) (PDEGMA-b-PDIPAEMA) were studied by static, dynamic and electrophoretic light scattering, small-angle X-ray scattering and differential scanning calorimetry. Thermoresponsive behavior of PDEGMA-b-PDIPAEMA was investigated at two pH values, pH = 2, at which the terminal carboxylic group of the PDEGMA chain and the PDIPAEMA block are protonated, and pH = 7, where the carboxyl terminal group is ionized while the PDIPAEMA block is partially deprotonated and more hydrophobic. Both at pH = 2 and 7, PDEGMA-b-PDIPAEMA copolymer underwent extensive association (the size of the aggregates was between 100 and 300 nm), indicating strong interchain interactions. While the measurements confirmed thermoresponsive behavior of PDEGMA-b-PDIPAEMA at pH = 7, no changes in the association with temperature were observed at pH 2 as the thermoresponsivity of PDEGMA was suppressed by hydrogen bonding between carboxylic groups and PDEGMA segments, as well as due to the increased hydrophilicity of the PDIPAEMA block. Fluorescence measurements with pyrene as a fluorescent probe showed that both at pH = 2 and pH = 7 the associates were able to solubilize hydrophobic substances. Full article

Thermoresponsive sol–gel transition polymers are of significant interest because of their fascinating biomedical applications, including as drug reservoirs for drug delivery systems and scaffolds for tissue engineering. Although extensive research has been conducted on lower critical solution temperature (LCST)-type sol–gel transition polymers, there have been few reports on upper critical solution temperature (UCST)-type sol–gel transition polymers. In this study, we designed an ABA-type triblock copolymer composed of a poly(ethylene glycol) (PEG) block and zwitterionic polymer blocks that exhibit UCST-type thermoresponsive phase transitions. A sulfobetaine (SB) monomer with both ammonium and sulfonate (–SO₃) groups in its side chain or a sulfabetaine (SaB) monomer with both ammonium and sulfate (–OSO₃) groups in its side chain was polymerized from both ends of the PEG block via reversible addition–fragmentation chain-transfer (RAFT) polymerization to obtain PSB-PEG-PSB and PSaB-PEG-PSaB triblock copolymers, respectively. Although an aqueous solution containing the PSB-PEG-PSB triblock copolymer showed an increase in viscosity upon cooling, it did not undergo a sol-to-gel transition. In contrast, a sol-to-gel transition was observed when a phosphate-buffered saline containing PSaB-PEG-PSaB was cooled from 80 °C to 25 °C. The PSaB blocks with –OSO₃ groups exhibited a stronger dipole–dipole interaction than conventional SB with –SO₃ groups, leading to intermolecular association and the formation of a gel network composed of PSaB assemblies bridged with PEG. The fascinating UCST-type thermoresponsive sol–gel transition properties of the PSaB-PEG-PSaB triblock copolymer suggest that it can provide a useful platform for designing smart biomaterials, such as drug delivery reservoirs and cell culture scaffolds. Full article

Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications. Full article

Thermo-responsive diblock copolymer, poly(N-isopropylacrylamide)-block-poly(N-vinylisobutyramide) was synthesized via switchable reversible addition–fragmentation chain transfer (RAFT) polymerization and its thermal transition behavior was studied. Poly(N-vinylisobutyramide) (PNVIBA), a structural isomer of poly(N-isopropylacrylamide) (PNIPAM) shows a thermo-response character but with a higher lower critical solution temperature (LCST) than PNIPAM. The chain extension of the PNVIBA block from the PNIPAM block proceeded in a controlled manner with a switchable chain transfer reagent, methyl 2-[methyl(4-pyridinyl)carbamothioylthio]propionate. In an aqueous solution, the diblock copolymer shows a thermo-responsive behavior but with a single LCST close to the LCST of PNVIBA, indicating that the interaction between the PNIPAM segment and the PNVIBA segment leads to cooperative aggregation during the self-assembly induced phase separation of the diblock copolymer in solution. Above the LCST of the PNIPAM block, the polymer chains begin to collapse, forming small aggregates, but further aggregation stumbled due to the PNVIBA segment of the diblock copolymer. However, as the temperature approached the LCST of the PNVIBA block, larger aggregates composed of clusters of small aggregates formed, resulting in an opaque solution. Full article

The group-transfer polymerization (GTP) of N,N-bis(2-methoxyethyl)acrylamide (MOEAm) initiated by Me₂EtSiH in the hydrosilylation-promoted method and by silylketene acetal (SKA) in the conventional method proceeded in a controlled/living manner to provide poly(N,N-bis(2-methoxyethyl)acrylamide) (PMOEAm) and PMOEAm with the SKA residue at the α-chain end (MCIP-PMOEAm), respectively. PMOEAm-b-poly(N,N-dimethylacrylamide) (PDMAm) and PMOEAm-s-PDMAm and PMOEAm-b-poly(N,N-bis(2-ethoxyethyl)acrylamide) (PEOEAm) and PMOEAm-s-PEOEAm were synthesized by the block and random group-transfer copolymerization of MOEAm and N,N-dimethylacrylamide or N,N-bis(2-ethoxyethyl)acrylamide. The homo- and copolymer structures affected the thermoresponsive properties; the cloud point temperature (T_cp) increasing by decreasing the degree of polymerization (x). The chain-end group in PMOEAm affected the T_cp with PMOEAm_x > MCIP-PMOEAm_x. The T_cp of statistical copolymers was higher than that of block copolymers, with PMOEAm_x-s-PDMAm_y > PMOEAm_x-b-PDMAm_y and PMOEAm_x-s-PEOEAm_y > PMOEAm_x-b-PEOEAm_y. Full article

Poly(glycerol monomethacrylate)-block-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) with worm-like morphology is a typical example of reversible addition–fragmentation chain transfer (RAFT) dispersion polymerized thermo-responsive copolymer via polymerization-induced self-assembly (PISA) in aqueous solution. Chain transfer agents (CTAs) are the key component in controlling RAFT, the structures of which determine the end functional groups of the polymer chain. It is therefore of interest to monofunctionalize the polymers via CTA moiety, for bioactive functionality conjugation and in the meantime maintain the precisely controlled morphology of the copolymers and the related property. In this work, a newly designed CTA 5-(2-(tert-butoxycarbonylamino) ethylamino)-2-cyano-5-oxopentan-2-yl benzodithioate (t-Boc CPDB) was synthesized and used for the RAFT polymerization of PGMA₄₅-PHPMA₁₂₀. Subsequently, PGMA₄₅-PHPMA₁₂₀ copolymers with primary amine, maleimide, and reduced L-glutathione (a tripeptide) monofunctionalized terminals were synthesized via deprotection and conjugation reactions. These monofunctionalized copolymers maintain worm-like morphology and thermo-responsive property in aqueous solution (10% w/v), as confirmed by the transmission electron microscopy (TEM) images, and the observation of the phase transition behavior in between 4 °C and room temperature (~20 °C), respectively. Summarily, a range of thermo-responsive monofunctionalized PGMA₄₅-PHPMA₁₂₀ diblock copolymer worms were successfully synthesized, which are expected to offer potential biomedical applications, such as in polymer therapeutics, drug delivery, and diagnostics. Full article

The development of composite materials with thermo-optical properties based on smart polymeric systems and nanostructures have been extensively studied. Due to the fact of its ability to self-assemble into a structure that generates a significant change in the refractive index, one of most attractive thermo-responsive polymers is poly(N-isopropylacrylamide) (PNIPAM), as well as its derivatives such as multiblock copolymers. In this work, symmetric triblock copolymers of polyacrylamide (PAM) and PNIPAM (PAM_x-b-PNIPAM_y-b-PAM_x) with different block lengths were prepared by reversible addition−fragmentation chain-transfer polymerization (RAFT). The ABA sequence of these triblock copolymers was obtained in only two steps using a symmetrical trithiocarbonate as a transfer agent. The copolymers were combined with gold nanoparticles (AuNPs) to prepare nanocomposite materials with tunable optical properties. The results show that copolymers behave differently in solution due to the fact of variations in their composition. Therefore, they have a different impact on the nanoparticle formation process. Likewise, as expected, an increase in the length of the PNIPAM block promotes a better thermo-optical response. Full article

This paper introduces a new class of amphiphilic block copolymers created by combining two polymers: polylactic acid (PLA), a biocompatible and biodegradable hydrophobic polyester used for cargo encapsulation, and a hydrophilic polymer composed of oligo ethylene glycol chains (triethylene glycol methyl ether methacrylate, TEGMA), which provides stability and repellent properties with added thermo-responsiveness. The PLA-b-PTEGMA block copolymers were synthesized using ring-opening polymerization (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization (ROP-RAFT), resulting in varying ratios between the hydrophobic and hydrophilic blocks. Standard techniques, such as size exclusion chromatography (SEC) and ¹H NMR spectroscopy, were used to characterize the block copolymers, while ¹H NMR spectroscopy, 2D nuclear Overhauser effect spectroscopy (NOESY), and dynamic light scattering (DLS) were used to analyze the effect of the hydrophobic PLA block on the LCST of the PTEGMA block in aqueous solutions. The results show that the LCST values for the block copolymers decreased with increasing PLA content in the copolymer. The selected block copolymer presented LCST transitions at physiologically relevant temperatures, making it suitable for manufacturing nanoparticles (NPs) and drug encapsulation-release of the chemotherapeutic paclitaxel (PTX) via temperature-triggered drug release mechanism. The drug release profile was found to be temperature-dependent, with PTX release being sustained at all tested conditions, but substantially accelerated at 37 and 40 °C compared to 25 °C. The NPs were stable under simulated physiological conditions. These findings demonstrate that the addition of hydrophobic monomers, such as PLA, can tune the LCST temperatures of thermo-responsive polymers, and that PLA-b-PTEGMA copolymers have great potential for use in drug and gene delivery systems via temperature-triggered drug release mechanisms in biomedicine applications. Full article

Thermal-responsive block copolymers are a special type of macromolecule that exhibit a wide range of applications in various fields. In this contribution, we report a new type of polyacrylamide-based block copolymer bearing pyridine groups of polyethylene glycol-block-poly(N-(2-methylpyridine)-acrylamide; Px) that display distinct salt-induced lower critical solution temperature (LCST) behavior. Unexpectedly, the phase-transition mechanism of the salt-induced LCST behavior of Px block copolymers is different from that of the reported LCST-featured analogues. Moreover, their thermo-responsive behavior can be significantly regulated by several parameters such as salt species and concentration, urea, polymerization degree, polymer concentration and pH values. This unique thermal behavior of pyridine-containing block copolymers provides a new avenue for the fabrication of smart polymer materials with potential applications in biomedicine. Full article

Colorectal cancer is the fourth most common cancer worldwide and the third most frequently diagnosed form of cancer associated with high mortality rates. Recently, targeted drug delivery systems have been under increasing attention owing to advantages such as high therapeutic effectiveness with a significant depletion in adverse events. In this report, we describe the biocompatible and thermoresponsive FA-conjugated PHEA-b-PNIPAAm copolymers as nanocarriers for the delivery of 5-FU. The block copolymers were obtained using RAFT (Reversible Addition–Fragmentation chain Transfer) polymerization and were characterized by methods such as SEC (Size Exclusion Chromatography), NMR (Nuclear Magnetic Resonance), UV–Vis (Ultraviolet–Visible), FT-IR (Fourier Transform Infrared) spectroscopy, and TGA (Thermogravimetric Analysis). Nanoparticles were formed from polymers with and without the drug-5-fluorouracil, which was confirmed using DLS (Dynamic Light Scattering), zeta potential measurements, and TEM (Transmission Electron Microscopy) imaging. The cloud points of the polymers were found to be close to the temperature of the human body. Eventually, polymeric carriers were tested as drug delivery systems for the safety, compatibility, and targeting of colorectal cancer cells (CRC). The biological evaluation indicated high compatibility with the representative host cells. Furthermore, it showed that proposed nanosystems might have therapeutic potential as mitigators for 5-FU-induced monocytopenia, cardiotoxicity, and other chemotherapy-associated disorders. Moreover, results show increased cytotoxicity against cancer cells compared to the drug, including a line with a drug resistance phenotype. Additionally, the ability of synthesized carriers to induce apoptosis and necrosis in treated CRC cells has been confirmed. Undoubtedly, the presented aspects of colorectal cancer therapy promise future solutions to overcome the conventional limitations of current treatment regimens for this type of cancer and to improve the quality of life of the patients. Full article

Polymeric micelle forming from self-assembly of amphiphilic macromolecules is one of the most potent drug delivery systems. Fatty acids, naturally occurring hydrophobic lipid components, can be considered as potential candidates for the fabrication of block copolymer micelles. However, examples of synthesis of responsive block copolymers using renewable fatty acids are scarce. Herein, we report the synthesis, characterization and testing of block copolymer micelles composed of a renewable fatty-acid-based hydrophobic block and thermoresponsive hydrophilic block for controlled drug delivery. The block copolymers of functionalized fatty acid and poly(N-isopropylacrylamide) (PNIPAM) were prepared via consecutive microwave-assisted reversible addition fragmentation chain transfer (RAFT) polymerization. The block copolymers with variable hydrophobic block length self-assembled in aqueous media and formed spherical nanoparticles of ~30 nm with low critical micelle concentration (CMC). To demonstrate the proof-of-concept, carbamazepine (CBZ) was used as a hydrophobic model drug to evaluate the performance of these micelles as nanocarriers. The in vitro drug release tests were carried out below (25 °C) and above (37 °C) the lower critical solution temperature (LCST) of the block copolymer. The drug release showed obvious temperature-triggered response and an accelerated drug release at 37 °C. Full article