Abstract:The reversible addition-fragmentation chain transfer (RAFT) of N-vinyl caprolactam (NVCL) using two new xanthates with alkyne functionalities is reported. The kinetic data obtained for polymerization of this non-activated monomer using a protected alkyne-terminated RAFT agent (PAT-X1) revealed a linear increase of the polymer molecular weight with the monomer conversion as well as low dispersity (Đ) during the entire course of the polymerization. The system reported here allowed us to enhance the final convers… Show more
“…Accordingly, the small difference between the calculated LCST may be related to the different end groups of the polymers under consideration. The presence of terminations or compounds that increase the hydrophilicity of PNVCL is known to increase the LCST [ 27 , 48 ]. Furthermore, PNVCL-COOH polymers with a 32°C LCST have been frequently used as starting polymers for the preparation of thermoresponsive particles [ 7 , 8 , 9 , 19 , 35 , 38 ].…”
Poly-N-Vinylcaprolactam (PNVCL) is a thermoresponsive polymer that exhibits lower critical solution temperature (LCST) between 25 and 50 °C. Due to its alleged biocompatibility, this polymer is becoming popular for biomedical and environmental applications. PNVCL with carboxyl terminations has been widely used for the preparation of thermoresponsive copolymers, micro- and nanogels for drug delivery and oncological therapies. However, the fabrication of such specific targeting devices needs standardized and reproducible preparation methods. This requires a deep understanding of how the miscibility behavior of the polymer is affected by its structural properties and the solution environment. In this work, PNVCL-COOH polymers were prepared via free radical polymerization (FRP) in order to exhibit LCST between 33 and 42 °C. The structural properties were investigated with NMR, FT-IR and conductimetric titration and the LCST was calculated via UV-VIS and DLS. The LCST is influenced by the molecular mass, as shown by both DLS and viscosimetric values. Finally, the behavior of the polymer was described as function of its concentration and in presence of different biologically relevant environments, such as aqueous buffers, NaCl solutions and human plasma.
“…Accordingly, the small difference between the calculated LCST may be related to the different end groups of the polymers under consideration. The presence of terminations or compounds that increase the hydrophilicity of PNVCL is known to increase the LCST [ 27 , 48 ]. Furthermore, PNVCL-COOH polymers with a 32°C LCST have been frequently used as starting polymers for the preparation of thermoresponsive particles [ 7 , 8 , 9 , 19 , 35 , 38 ].…”
Poly-N-Vinylcaprolactam (PNVCL) is a thermoresponsive polymer that exhibits lower critical solution temperature (LCST) between 25 and 50 °C. Due to its alleged biocompatibility, this polymer is becoming popular for biomedical and environmental applications. PNVCL with carboxyl terminations has been widely used for the preparation of thermoresponsive copolymers, micro- and nanogels for drug delivery and oncological therapies. However, the fabrication of such specific targeting devices needs standardized and reproducible preparation methods. This requires a deep understanding of how the miscibility behavior of the polymer is affected by its structural properties and the solution environment. In this work, PNVCL-COOH polymers were prepared via free radical polymerization (FRP) in order to exhibit LCST between 33 and 42 °C. The structural properties were investigated with NMR, FT-IR and conductimetric titration and the LCST was calculated via UV-VIS and DLS. The LCST is influenced by the molecular mass, as shown by both DLS and viscosimetric values. Finally, the behavior of the polymer was described as function of its concentration and in presence of different biologically relevant environments, such as aqueous buffers, NaCl solutions and human plasma.
“…CPP-CS- co -PNVCL 1 was transparent at the physiological temperature (37 °C) but became turbid once the temperature was raised to 40 °C. This phenomenon can be attributed to the disruption of hydrogen bonding with water and increasing hydrophobic interactions between the caprolactam groups at higher temperatures [26, 35]. Given it had the most appropriate LCST for the intended application, CPP-CS- co -PNVCL 1 was employed in all subsequent experiments.Fig.…”
Background
It is extremely difficult to develop targeted treatments for triple-negative breast (TNB) cancer, because these cells do not express any of the key biomarkers usually exploited for this goal.
Results
In this work, we develop a solution in the form of a cascade responsive nanoplatform based on thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs). These are further modified with the cell penetrating peptide (CPP) and loaded with the chemotherapeutic drug doxorubicin (DOX). The base copolymer was optimized to undergo a phase change at the elevated temperatures of the tumor microenvironment. The acid-responsive properties of CS provide a second trigger for drug release, and the inclusion of CPP should ensure the formulations accumulate in cancerous tissue. The resultant CPP-CS-co-PNVCL NPs could self-assemble in aqueous media into spherical NPs of size < 200 nm and with low polydispersity. They are able to accommodate a high DOX loading (14.8% w/w). The NPs are found to be selectively taken up by cancerous cells both in vitro and in vivo, and result in less off-target cytotoxicity than treatment with DOX alone. In vivo experiments employing a TNB xenograft mouse model demonstrated a significant reduction in tumor volume and prolonging of life span, with no obvious systemic toxicity.
Conclusions
The system developed in this work has the potential to provide new therapies for hard-to-treat cancers.
“…PNVCL is a nonionic, nontoxic, water‐soluble, thermoresponsive, and biocompatible polymer 21‐24 . Although the lower critical solution temperature (LCST) of PNVCL is close to LCST of poly( N ‐isopropylacrylamide) (PNIPAM), the most representative thermoresponsive polymer, there are significant differences in the thermodynamic and molecular mechanisms underlying the phase transition 25,26 . In comparison with PNIPAM, PNVCL has some obvious advantages, such as lower interaction with biomolecules and no tendency to crystallize 27 .…”
The first‐ and second‐generation well‐defined thermal and enzymatic dual‐stimuli responsive amphiphilic linear‐dendritic block copolymers (LDBCs) based on hydrophilic linear poly(N‐vinylcaprolactam) (PNVCL) and a hydrophobic Fmoc‐terminated dendron derived from an aliphatic polyester of 2, 2′‐dimethylolpropionic acid (bis‐MPA) have been synthesized via a combination of reversible addition fragmentation chain transfer (RAFT) polymerization of N‐vinylcaprolactam (NVCL) and “chain‐first” strategy. The copolymers were characterized by 1H NMR spectra and gel permeation chromatograph (GPC) analyses, showing controlled molecular weight and narrow molecular weight distribution (PDI ≤1.27). They self‐assemble in water into vesicles that are able to disrupt and release encapsulated cargos upon papain treatment. Their thermal‐responsive property was highly dependent on the generation and concentration of copolymers, and enzyme‐responsive behavior was affected by the generation of dendritic aliphatic polyester block. Moreover, papain influenced the thermal‐responsive behavior of the copolymers. Such smart copolymers could be efficiently used in drug delivery systems or biosensors.
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