Fully bio-based hydroxy ester vitrimer synthesized by crosslinking epoxidized soybean oil with doubly esterified starch.

Catalyst-free fully bio-based hydroxyester (BHE) vitrimers were synthesized by crosslinking and plasticizing epoxidized soybean oil with synthesized acetylated starch succinate monoesters to investigate the effects of different starch structures on the properties of the BHE vitrimers. The BHE vitrimers possessed a lower glass transition temperature as well as better solvent resistance and reprocessing performance compared to traditional starch-based materials. Owing to dynamically covalent bonds, the migration and exudation of plasticizers were avoided. A maximum strain of 230 % was achieved to prevent the retrogradation and brittleness of starch-based materials. Furthermore, the mechanical properties remained unchanged after three reprocessing cycles. Consequently, the obtained BHE vitrimers are eco-friendly and sustainable.

pH-sensitive, tail-modified, ester-linked ionizable cationic lipids for gene delivery.

Ionizable cationic lipids have great potential for gene delivery, yet the effect of the molecular structure of such lipids on gene delivery efficiency is an ongoing research challenge. To better understand corresponding structure-function activity relationships, we synthesized four ester-linked, pH-responsive, ionizable cationic lipids. The screened DEDM4 lipid, containing 2-ethylenedimethylamine in the headgroup and a branched-chain tail, exhibited a high delivery efficacy of plasmid DNA and siRNA in A549 cells, which was comparable with that of the commercial reagent lipofectamine 3000 (lipo3000). Moreover, because of its pKa value of 6.35 and pH-sensitivity under acidic conditions, DEDM4 could carry sufficient positive charge in the acidic environment of endosomes and interact with the endosome lumen, leading to destruction of the endomembrane and subsequent release of siRNA into the cytoplasm with endosomal escape. Furthermore, we used DEDM4 to deliver IGF-1R siRNA to induce cancer cell apoptosis, thereby leading to great tumor inhibition. More importantly, it also showed very low toxicity in vivo. These structure-activity data for DEDM4 demonstrate potential clinical applications of DEDM4-mediated gene delivery for cancer.

Cationic Nanoparticulate System for Codelivery of MicroRNA-424 and Podophyllotoxin as a Multimodal Anticancer Therapy.

Because of the complexity of cancer ecosystems, the efficacy of single-agent chemotherapy is limited. Herein, we report the use of cationic nanoparticles (designated PPCNs) generated from a chemically modified form of the chemotherapeutic agent podophyllotoxin (PPT) to deliver both microRNA-424 (miR-424) and PPT to tumor cells, thus combining chemotherapy and gene therapy. We evaluated the optimal loading ratio of miR-424─which targets programmed cell death ligand 1 (PD-L1) mRNA and reduces PD-L1 production, thus promoting the attack of tumor cells by T cells─for effective delivery of miR-424 and PPCNs into nonsmall-cell lung cancer cells (H460). Because miR-424 can reverse chemotherapy resistance, treatment of the tumor cells with the combination of miR-424 and PPT enhanced their sensitivity to PPT. Because miR-424 and the PPCNs regulated PD-L1 production in different ways, the miR-424@PPCN complexes were significantly more efficacious than either miR-424 or PPCNs alone. We also demonstrated that treatment of tumor-bearing mice with these complexes significantly inhibited tumor growth and extended survival. Moreover, additional in vitro experiments revealed that the complexes could remodel the tumor immune microenvironment, relieve immunosuppression, and achieve immune normalization. This novel system for delivering a combination of PPT and miR-424 shows great potential for the multimodal treatment of lung cancer.

Bioinspired Polypeptide Photonic Films with Tunable Structural Color.

We report a new synthetic strategy of combining N-carboxyanhydride (NCA) chemistry and photonic crystals for the fabrication of polypeptide structural color films. Driven by surface-initiated ring-opening polymerization, the di-NCA derivative of l-cystine (Cys) is introduced to replicate the functionalized colloidal crystal templates and construct freestanding P(Cys) films with tunable structural color. Furthermore, the feasibility of preparing patterned polypeptide photonic films is demonstrated via template microfabrication. Because of the incorporation of l-glutamate (Glu) components, the P(Cys-co-Glu) co-polypeptide films are endowed with a visual color responsiveness toward pH changes. Additionally, the polypeptide photonic films show on-demand degradability. Given the large family of amino acid building blocks, this powerful and versatile approach paves the way for chemical derivatization of multifunctional peptide-based optical platforms.

Self-Assembly of Podophyllotoxin-Loaded Lipid Bilayer Nanoparticles for Highly Effective Chemotherapy and Immunotherapy via Downregulation of Programmed Cell Death Ligand 1 Production.

Low drug delivery efficiency elevates the cost of medication, lowers the therapeutic efficacy, and appears as a leading reason for unmet needs in anticancer therapies. Herein, we report the development of self-assembled podophyllotoxin-loaded lipid bilayer nanoparticles that inhibit the production of programmed cell death ligand 1 in lung cancer cells and promote tumor-specific immune responses, thus offering a strategy for regulating the immunosuppressive microenvironment of tumors. In addition, encapsulation of podophyllotoxin in the nanoparticles reduced its systemic toxicity, enhanced its penetration into tumors, and increased its antitumor efficacy. Systemic injection of the nanoparticles into tumor-bearing mice not only prevented tumor immune escape but also significantly inhibited tumor growth and extended survival. In general, the podophyllotoxin-loaded nanoparticles exhibited both immunological effects and antitumor effects in addition to having better targeting activity and fewer side effects than free podophyllotoxin. We expect our findings to facilitate the development of therapies for lung cancer.

Structure-activity relationships of pH-responsive and ionizable lipids for gene delivery.

Ionizable lipids are the leading vectors for gene therapy. Understanding the effects of molecular structure on efficient gene delivery is one of the most important challenges for maximizing the utility of such lipid vectors. We synthesized an array of pH-responsive and ionizable lipids to investigate the relationship between lipid structure and activity. The optimized lipid (EDM) has double tertiary amines in the headgroup and an ester linker. EDM exhibited efficient DNA and siRNA delivery to, and gene silencing of, A549 cells. EDM has a pKa value of 6.67, which enabled it to quickly escape from the endosome after entering the cell; the ester linkages rapidly degraded and enabled gene release into the cytoplasm. EDM also delivered IGF-1R siRNA to inhibit tumor growth and induce cancer cell apoptosis by efficient inhibition of IGF-1R expression in mice. Our study on the structure-activity relationships of ionizable lipids will facilitate clinical applications.

Preparation of thermoresponsive alginate/starch ether composite hydrogel and its application to the removal of Cu(II) from aqueous solution.

A novel polysaccharide-based thermoresponsive hydrogel containing sodium alginate (SA) and 2-hydroxy-3-isopropoxypropyl starch (HIPS) was developed for removing Cu(II) from aqueous solution. HIPS/SA hydrogel showed network and porous structure, as well as the abundant carboxy groups inside the structure, endowed it with sufficient binding sites for adsorption of Cu(II). The reversible thermoresponsive swelling-shrinking behavior of HIPS/SA hydrogel was discussed. The effects of pH and initial Cu(II) concentration on adsorption capacity were investigated. The adsorption isotherms and kinetics of HIPS/SA hydrogel demonstrated that the adsorption of Cu(II) was subjected to Langmuir and pseudo-second-order models respectively, and the maximum adsorption capacity was 25.81 mg/g. Additionally, HIPS/SA hydrogel could be successfully desorbed by only small amounts of dilute hydrochloric acid within a short time for its thermoresponsive property, it also exhibited the feasibility of regeneration, because the adsorption capacity for Cu(II) was still higher than 15.23 ±â€¯0.27 mg/g even after five cycles.

A green l-cysteine modified cellulose nanocrystals biosorbent for adsorption of mercury ions from aqueous solutions.

Using a green biosorbent to remove toxic mercury ions from aqueous solutions is a significant undertaking. In the present study, a novel biosorbent, l-cysteine modified cellulose nanocrystals (Lcys-CNCs), was prepared by functionalizing high surface area cellulose nanocrystals with l-cysteine through periodate oxidation and reductive amination reaction. Lcys-CNCs were characterized by FT-IR, 13C CP-MAS NMR, elemental analysis, XPS, zeta potential and SEM. As cellulose nanocrystals are the natural nanomaterial, and l-cysteine contains strong mercury chelating groups, Lcys-CNCs show excellent adsorption capacity for mercury ions. The experimental conditions such as pH, contact time, and initial mercury ion concentration are discussed. The pseudo-second order model can describe the removal kinetics of Hg(ii) more accurately than the pseudo-first order model. The adsorption isotherm study of Hg(ii) followed the Langmuir model of monolayer adsorption. The maximum uptake capacity of Lcys-CNCs was determined to be 923 mg g-1. Lcys-CNCs can remove mercury ions with 93% removal efficiency within 5 min from a 71 mg L-1 solution. For Cd(ii), Pb(ii), Cu(ii) and Zn(ii) ions, Lcsy-CNCs can selectively adsorb Hg(ii) ions and the removal efficiency is 87.4% for Hg(ii). This study suggests Lcsy-CNCs are a green and highly efficient biosorbent for adsorption of mercury ions from aqueous solutions.

Synthesis of pH-responsive N-acetyl-cysteine modified starch derivatives for oral delivery.

In this study, a novel type of pH-responsive polymer PyHES-NAC (2-hydroxy-3-(2-propynyloxy) propyl hydroxyethyl starch (PyHES)) - (N-acetyl-cysteine (NAC)) was synthesized. First, PyHES was prepared via hydrophobic modification of hydroxyl groups in hydroxyethyl starch (HES) with propynylglycidyl ether (PGE), and then pH-responsive carboxylic acid group was connected to propynyl group via thiol-yne click reaction with NAC. Aqueous PyHES-NAC solutions exhibited a good transference between hydrophobic (or self-assembly) and hydrophilic static along with the change of pH value and protective properties of drugs under acidic conditions. 10.0% DOX was released under artificial gastric fluid after 2 h, whereas an immediate release (above 80%) was observed under artificial intestinal fluid. Drug loading capacity of PyHES-NAC was increased by the increase of degree of substitution (DS) of hydrophobic propynyl groups in PyHES, and 41 wt% DOX Loading capacity was the highest value in our study area.

Thermoresponsive cellulose ether and its flocculation behavior for organic dye removal.

A thermoresponsive polymer, 2-hydroxy-3-butoxypropyl hydroxyethyl cellulose (HBPEC), was prepared by grafting butyl glycidyl ether (BGE) onto hydroxyethyl cellulose (HEC). The lower critical solution temperature (LCST) and critical flocculation temperature (CFT) of HBPEC were varied by changing the molar substitution (MS) and salt concentrations. Transmission electron microscopy (TEM) images and fluorescence spectroscopy showed that HBPEC can assemble into micelles. Additionally, using Nile Red as a model dye, the performance of HBPEC for the removing Nile Red from aqueous solutions via cloud point extraction procedures was investigated in detail. The encapsulation behavior of dye in the aqueous solution of HBPEC was studied by fluorescence spectroscopy and fluorescence microscope. The experimental results indicated that 99.4% of dye was removed from the aqueous solutions, and the HBPEC was recycled and reused easily, Furthermore, the recycle efficiency (RE) and maximum loading capacity portrayed little loss with the number of cycles.

Easy approach to assembling a biomimetic color film with tunable structural colors.

The self-assembly of silica microspheres into a close-packed array is a simple method of fabricating three-dimensional photonic crystal structural color films. However, the color is very dull because of the interferences of scattering and background light. In this study, we added a small quantity of surface-modified carbon black (CB) to the system of colloidal silica in n-propanol. The use of n-propanol as a dispersant is beneficial to the rapid development of photonic crystal films during the process of dip-coating. The doping of CB into silica microspheres can absorb background and scattering light, resulting in vivid structural colors.

Novel pH- and temperature-responsive polymer: tertiary amine starch ether.

A novel double pH- and temperature-responsive tertiary amine starch ether (TAS) has been developed. Synthesis was performed by grafting dipropyl or dibutyl epoxypropylamine onto hydroxyethyl starch. The cloud point temperatures (TC) of TAS could be tuned to a wide range from 26 to 72.8°C by changing the alkyl chain length, their average molar substitution (MS), and pH value of the solution. The TC of TAS increases with decreasing the alkyl chain length, MS, and pH value of the solution. A linear relationship occurs between the TC and the pH, indicating well-tunable TC. These TAS also showed single pH-sensitive property due to the existence of tertiary amino and hydrophobic alkyl groups. The synthetic strategy presented here could be employed in the preparation of other novel biomaterials with dual pH- and temperature-responsive properties from a variety of polysaccharides.

Thermoresponsive starch derivates with widely tuned LCSTs by introducing short oligo(ethylene glycol) spacers.

Water soluble, thermoresponsive 3-[2-butoxy(ethoxy)m]-2-hydroxypropyl starch ethers (BEmS) (m=0, 1, or 2) were prepared by reacting degraded waxy maize starch with n-butyl glycidyl ether, 3-(2-n-butoxyethyl) glycidyl ether, and 3-[2-(2-n-butoxyethoxy)ethyl] glycidyl ether, respectively. The lower critical solution temperatures (LCSTs) of BEmS could be tuned to a wide range from 17.5°C to 55.0°C by changing the side chain lengths of oligo(ethylene glycol) groups and their average molar substitution (MS). The LCSTs of BEmS increase with increasing side chain length of oligo(ethylene glycol) groups when BS, BES, and BE2S have similar MS values. By contrast, an increase in BEmS concentration and addition of NaCl to the BEmS solutions could lead to a decrease in the LCSTs of BEmS. In addition, the effects of NaCl and BEmS concentrations on the LCSTs become weaker when the side chain length of oligo(ethylene glycol) groups increase.