Aliphatic Hyperbranched Polycarbonates Solid Polymer Electrolytes with High Li-Ion Transference Number for Lithium Metal Batteries.

In this work, hyperbranched polycarbonate-poly(ethylene oxide) (PEO)-based solid polymer electrolytes (HBPC-SEs) are successfully synthesized via a straightforward organo-catalyzed "A1"+"B2"-ring-opening polymerization approach. The temperature-dependent ionic conductivity of HBPC-SEs, composed of different polycarbonate linkages and various LiTFSI concentrations, is investigated. The results demonstrate that HBPC-SE with an ether-carbonate alternating structure exhibits superior ionic conductivity, attributed to the solubility of Li salts in the polymer matrix and the mobility of the polymer segments. The HBPC1-SE with 30 wt% LiTFSI presents the highest ionic conductivities of 2.15  × 10-5, 1.78 × 10-4, and 6.07 × 10-4 Scm-1 at 30, 60, and 80 °C, respectively. Compared to traditional PEO-based electrolytes, the incorporation of polycarbonate segments significantly enhances the electrochemical stability window (5 V) and Li+ transference number (0.53) of HBPC-SEs. Furthermore, the LiFePO4/HBPC1-SE-3/Li cell exhibits exceptional rate capability and long-cycling performance, maintaining a discharge capacity of 130 mAh g-1 at 0.5C with a capacity retention of 95% after 300 cycles.

Synthesis of Functional Isosorbide-Based Polyesters and Polyamides by Passerini Three-Component Polymerization.

Environmental issues are becoming more and more prominent, and bio-based polymers are essential to alleviate environmental degradation by replacing traditional polymers. With this context, a new family of functional isosorbide-based polyesters and polyamides with high glass transition temperature are prepared via Passerini-Three component polymerization (P-3CP). To optimize the P-3CP conditions, the influence of the polymerization solvent, temperature, feed ratio on the molar mass of final polymers are investigated. The higher molar mass (up to 10100 g/mol) and yield (>70 %) are achieved under very mild conditions (30 °C, standard atmosphere). Functional side groups, such as alkenyl, alkynyl and methyl ester, were introduced into polymer structure via P-3CP by using functional isocyanides. The obtained polyesters and polyamides are characterized by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopies, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). All polymers are thermal stable and amorphous with variable glass transition temperatures (Tg ). The obtained polyester has Tg up to 87.5 °C, while the Tg of polyamides (ISPA-2) is detected to be 97.5 °C depending on the amide bonds in the polymer backbone and the benzene ring side groups. The cytotoxicity is investigated by the CCK-8 assay against mBMSC cells to confirm the biological safety. Overall, this novel strategy provides an efficient approach to produce functional isosorbide-based polyesters and polyamides, which are promising prospect for being applied to biodegradable materials.

Preparation of PFPE-Based Polymeric Nanoparticles via Polymerization-Induced Self-Assembly as Contrast Agents for 19F MRI.

Fluorine-19 magnetic resonance imaging (19F MRI) probes have received considerable research interest as imaging contrast agents (CAs), but they remain neglected and underutilized due to the limited fluorine content or poor performance of fluorinated tracers. Here, we present polymeric nanoparticles (NPs) as 19F MRI CAs with a simple synthesis method and promising imaging performance. First, hydrophilic random copolymers were synthesized from oligo(ethylene glycol) methyl ether acrylate and perfluoropolyether methacrylate by reversible addition-fragmentation chain transfer (RAFT) polymerization. The optimal fluorine content, polymer concentration, and cytotoxicity as 19F MRI CAs were investigated in detail. Then, the optimal copolymer was selected as the macromolecular chain transfer agent, and the chain extension was performed with 2-(perfluorooctyl ethyl methacrylate). Subsequently, the NPs with different morphologies, such as ellipsoidal, spherical nanoparticles and vesicles, were prepared in situ by the RAFT-mediated polymerization-induced self-assembly method. In addition, the 19F MRI signal and cytotoxicity studies further confirmed that these polymeric NPs are nontoxic and have great potential as promising 19F MRI CAs for biological applications.

Photo-Responsive Self-Assembled Polymeric Nanoparticle Probes for 19F MRI Theranostics.

19F magnetic resonance imaging (MRI)-assisted drug delivery provides the possibility to monitor and track drug transportation details in situ. A series of photo-responsive amphiphilic block copolymers consisting of hydrophilic poly(ethylene glycol) and 19F-containing hydrophobic segments, poly(2,2,2-trifluoroethyl acrylate) (PTFEA), with different chain lengths were synthesized by reversible addition-fragmentation chain-transfer polymerization. In particular, the photo-sensitive functional group of o-nitrobenzyl oxygen was introduced to control the photolysis behavior of the copolymers under ultraviolet irradiation. With the extension of the hydrophobic chain length, the drug loading capacity and photoresponsivity were both enhanced, while the chain mobility of PTFEA was suppressed, and the 19F MRI signal was attenuated. When the polymerization degree of PTFEA was about 10, the nanoparticles exhibit detectable 19F MRI signals and sufficient drug loading capacity (loading efficiency = 10%, cumulative release = 49%). These results offer a promising "smart" theranostic platform for 19F MRI.

Remote Light-Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives.

Engineering of smart photoactivated nanomaterials for targeted drug delivery systems (DDS) has recently attracted considerable research interest as light enables precise and accurate controlled release of drug molecules in specific diseased cells and/or tissues in a highly spatial and temporal manner. In general, the development of appropriate light-triggered DDS relies on processes of photolysis, photoisomerization, photo-cross-linking/un-cross-linking, and photoreduction, which are normally sensitive to ultraviolet (UV) or visible (Vis) light irradiation. Considering the issues of poor tissue penetration and high phototoxicity of these high-energy photons of UV/Vis light, recently nanocarriers have been developed based on light-response to low-energy photon irradiation, in particular for the light wavelengths located in the near infrared (NIR) range. NIR light-triggered drug release systems are normally achieved by using two-photon absorption and photon upconversion processes. Herein, recent advances of light-responsive nanoplatforms for controlled drug release are reviewed, covering the mechanism of light responsive small molecules and polymers, UV and Vis light responsive nanocarriers, and NIR light responsive nanocarriers. NIR-light triggered drug delivery by two-photon excitation and upconversion luminescence strategies is also included. In addition, the challenges and future perspectives for the development of light triggered DDS are highlighted.

Light-Responsive Serinol-Based Polyurethane Nanocarrier for Controlled Drug Release.

In the present work, a new and facile strategy for the synthesis of light-responsive polyurethanes (LrPUs) based on serinol with o-nitrobenzyl pendent groups is developed. Stable monodisperse nanoparticles from these LrPUs can be formulated reproducibly in a simple manner, which is shown by dynamic light scattering (DLS) measurements. Upon irradiation with UV light, both polymers and nanoparticles undergo rapid degradation, which is investigated by DLS, scanning electron microscopy, size exclusion chromatography, and UV-vis spectroscopy. The nanoparticles are also employed for the encapsulation of the model drug Nile Red, and by exposure to UV light, a burst release of the payload is detected via fluorescence spectroscopy. This strategy can be easily applied to the straightforward synthesis of various new serinol-based monomers with different stimuli-responsive properties and therefore expand the family of biodegradable polymers.

Use of Light-Degradable Aliphatic Polycarbonate Nanoparticles As Drug Carrier for Photosensitizer.

Aliphatic poly(carbonate)s (APCs) with rapid and controlled degradation upon specific stimulation have great advantages for a variety of biomedical and pharmaceutical applications. In the present work, we reported a new poly(trimethylene carbonate) (PTMC)-based copolymer containing multiple 4,5-dimethoxy-2-nitrobenzyl photo cleavable groups as pendent chains. The six-membered light-responsive cyclic carbonate monomer (LrM) was first prepared from 2-(hydroxymethyl)-2-methylpropane-1,3-diol and 4,5-dimethoxy-2-nitrobenzyl alcohol and then copolymerized with trimethylene carbonate (TMC) by 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) catalyzed ring-opening polymerization (ROP) to afford the light-responsive polycarbonate (LrPC). The light-triggered decomposition of LrM and LrPC was studied by NMR, UV/vis spectroscopy, and size exclusion chromatography (SEC), as well as ESI-ToF mass spectrometry. Stable monodisperse nanoparticles with hydrodynamic diameter of 100 nm could be formulated from 25% LrPC and 75% poly(lactide- co-glycolide) (PLGA) and applied for the encapsulation of temoporfin. Upon irradiation with UV light these particles displayed a significant decrease of the particle countrate and increased the release rate of temoporfin in comparison to standard PLGA nanoparticles. This work demonstrated that a combination of encapsulation of photosensitizer and light degradation using light-responsive polymers is suitable to enhance photodynamic therapy (PDT).

In vitro evaluation of innovative light-responsive nanoparticles for controlled drug release in intestinal PDT.

Nanoparticles (NP) have gained importance as drug delivery systems for pharmaceutical challenging drugs. Their size properties allow passive targeting of cancer tissue by exploiting the enhanced permeability and retention (EPR) effect. Furthermore, surface modifications enable an active drug targeting for diseased regions in the human body. Besides the advantages, the drug release from commonly used biodegradable NP is mostly depending on physiological circumstances. Hence, there is a need for a more controllable drug release. The use of light-responsive polymers is an innovative conception enabling a more distinct drug release by an external light stimulus. The idea provides potential for an increase in efficiency and safety of local therapies. In this study, innovative light-sensitive NP were investigated for a photodynamic therapy (PDT) of gastrointestinal tumors. Nanoparticles based on a newly developed light-responsive polycarbonate (LrPC) and poly(lactic-co-glycolic-acid) (PLGA) were loaded with the approved photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (mTHPC). Mucus penetrating properties were obtained by surface PEGylation of the nanoparticles either by using LrPC in combination with a PEGylated PLA (PEG-PLA) or by a combination with PEGylated LrPC (LrPC-PEG). Cytotoxic potential in dependency of a light-induced drug release was investigated in different cytotoxicity assays. Intracellular accumulation in mucus producing colon-carcinoma cell line HT-29-MTX was analysed by HPLC and confocal laser microscopy.

Light-responsive nanoparticles based on new polycarbonate polymers as innovative drug delivery systems for photosensitizers in PDT.

Nanoparticles based on biodegradable polymers are well-known as approved carrier systems for a diversity of drugs. Despite their advantages, such as the option of an active drug targeting or the physicochemical protection of instable payloads, the controlled drug release often underlies intra- and interindividual influences and is therefore difficult to predict. To circumvent this limitation, the release behavior can be optimized using light-responsive materials for the nanoparticle preparation. The resulting light-responsive nanoparticles are able to release the embedded drug after an external light-stimulus, thereby increasing efficacy and safety of the therapy. In the present study light-responsive self-immolative polymers were used for the nanoparticle manufacturing. Light-responsive polycarbonates (LrPC) as well as PEGylated LrPC (LrPC-PEG) were synthesized via ring-opening polymerization of trimethylene carbonate-based monomers and fully physico-chemically characterized. Light-responsive nano formulations were obtained by blending LrPC or (LrPC-PEG) with the FDA-approved polymer poly(DL-lactide-co-glycolide) (PLGA). The nanoparticles were loaded with the photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (mTHPC). The light-induced nanoparticle degradation was analyzed as well as the drug release behavior with and without illumination. Furthermore, biological safety of the degradation products was investigated in an in vitro cell culture study.

Light-Responsive Serinol-Based Polycarbonate and Polyester as Degradable Scaffolds.

Stimuli-responsive self-immolative aliphatic polycarbonates (APCs) and polyesters (APEs) have attractive advantages for biomedical and pharmaceutical applications. In the present work, polycondensation of o-nitrobenzyl-protected serinol was explored as a simple route to obtain light-responsive polycarbonate (LrPC) and polyester (LrPE). By exposure to UV light, these polymers decomposed rapidly and completely into oligomers and small molecules, as detected by size exclusion chromatography (SEC), UV/vis, and 1H nuclear magnetic resonance (NMR) spectroscopies. The degradation mechanism of serinol-based APC and APE was investigated with the help of the Boc-protected model APC and APE, showing that the APC underwent intramolecular cyclization, accompanied by intermolecular transcarbamation, and degraded into oxazolidinone and 2-aminopropanol terminated oligourethanes. Different from APC, the degradation process of serinol-based APE has been proven by electrospray ionization time-of-flight mass spectrometry (ESI-ToF-MS) to follow intramolecular cyclization of the functional amine group with the remote ester group, forming a ten-membered cyclic degradation compound. Further processing of the serinol-based polymers was performed by preparation of nanoparticles (NP). With light-responsive characteristics, a drug delivery system could be potentially obtained enabling a controllable drug release. Based on this strategy, a variety of self-immolative polymers responsive to different triggers can be prepared by polycondensation without the limit of ring-opening polymerization and will expand the family of biodegradable polymers.

Safety assessment of freeze-dried powdered Cassiae Semen: evaluation of chronic toxicity (26-week) in Sprague-Dawley rats.

There is a lack of safety assessment data regarding the long-term consumption of Cassiae Semen (Leguminosae, the seeds of Cassia obtusifolia L. and Cassia tora L.). Thus, we evaluated the toxicity of freeze-dried powdered Cassiae Semen in male and female Sprague-Dawley rats. Rats were intragastrically administered freeze-dried powdered Cassiae Semen at a dose of 0.5, 2.2, or 10.0 g/kg body weight/day for 26 weeks; several variables were assessed after 13 and 26 weeks as well as after a 4-week recovery period. No mortality was observed in the treated animals, and body weight increased in a dose-dependent manner. The total bilirubin (TBIL) levels also displayed a dose-dependent relationship. In males, at 26 weeks, there were significant increases in relative kidney weights in the 2.2 and 10.0 g/kg groups compared with that in the negative control group (p < 0.05 or p < 0.01). Pigment deposition in the epithelial cells of the renal proximal convoluted tubules and atrophy or regeneration of renal tubules were observed in the 10.0 g/kg group after 26 weeks, and these changes were not fully reversed after the 4-week recovery period. Under the studied conditions, the primary toxicity organs for freeze-dried powdered Cassiae Semen in the 10.0 g/kg group were the kidneys.