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Hibernation is one of the fundamental strategies in response to cold environmental temperatures. During hibernation, the endocrine and circadian systems ensure minimal expenditure of energy for survival. The circadian rhythms of key hormones, melatonin (MT), corticosterone (CORT), triiodothyronine (T3 ), and thyroxine (T4 ), and the underlying molecular regulatory mechanisms of hibernation have been well determined in mammals but not in ectotherms. Here, a terrestrial hibernating species, Asiatic toad (Bufo gargarizans), was employed to investigate the plasma CORT, MT, T3 , and T4 ; and the retina, brain, and liver mRNA expression of the core clock genes, including circadian locomotor output cycles kaput (Clock), brain and muscle ARNT-like 1 (Bmal1), cryptochrome (Cry) 1 and 2, and period (Per) 1 and 2, at seven-time points over a 24-hr period under acute cold (1 day at 4 °C), and hibernation (45 days at 4 °C). Our results showed that the circadian rhythms of the core clock genes were rather unaffected by acute cold exposure in the retina, unlike the brain and liver. In contrast, during hibernation, the liver clock genes displayed significant circadian oscillations, while those in the retina and brain stopped ticking. Furthermore, plasma CORT expressed circadian oscillations in both groups, and T3 in acute cold exposure group, whereas T4 and MT did not. Our results reveal that the plasma CORT and the liver sustain rhythmicity when the brain was not, indicating that the liver clock along with the adrenal clock synergistically maintains the metabolic requirements to ensure basic survival in hibernating Asiatic toads. This article is protected by copyright. All rights reserved.

The innate hypoxic microenvironment of most solid tumors has a major influence on tumor growth, invasiveness, and distant metastasis. Here, a hypoxia-activated self-immolative prodrug of paclitaxel (PTX2 -Azo) was synthesized and encapsulated by a peptide copolymer decorated with the photosensitizer chlorin e6 (Ce6) to prepare light-boosted PTX nanoparticle (Ce6/PTX2 -Azo NP). In this nanoparticle, PTX2 -Azo prevents premature drug leakage and realizes specific release in hypoxic tumor microenvironment and the photosensitizer Ce6 not only efficiently generates singlet oxygen under light irradiation but also acts as a positive amplifier to promote the release of PTX. The combination of photodynamic therapy (PDT) and chemotherapy results in excellent antitumor efficacy, demonstrating the great potential for synergistic cancer therapy.

Metal-organic frameworks (MOFs) formed by coordination between metal ions or clusters and organic bridging ligands possess great potential for biomedicine applications, given their high biocompatibility and biodegradability. Compared with the traditional three-dimensional (3D) MOFs, two-dimensional (2D) MOFs with sheet-like morphologies exhibit unique properties. In this study, a nanoscale 2D leaf-shaped MOF (NZIF-L) was synthesized via coordination self-assembly between 2-methylimidazole (Hmim) and Zn2+ with subsequent morphology and size control. The fabricated NZIF-L is cytocompatible and can be quickly endocytosed, which makes it an excellent cargo carrier. Subsequent to loading with either doxorubicin (DOX) or 4,4'-(1,2-diphenylvinyl)-1,2-di-(phenylcarboxylic acid) (TCPE), the respectively obtained DOX@NZIF-L and TCPE@NZIF-L showed promise for killing and imaging cancer cells.

A fluorescent, diselenide-containing 9,10-distyrylanthracene (DSA) derivative (SeDSA) with aggregation-induced emission (AIE) characteristic was successfully synthesized and SeDSA nanoparticles (NPs) were prepared through a nanoprecipitation method. SeDSA could coassemble with an antitumor prodrug, diselenide-containing paclitaxel (SePTX), which could be obtained by precipitation, to form SeDSA-SePTX Co-NPs (Co-NPs). Molecular dynamics (MD) simulations reveal that the driving forces for the self-assembly behaviors of SeDSA NPs and SePTX NPs are π-π interactions and hydrophobic interactions, respectively, while the driving forces for Co-NPs include hydrophobic interactions between SeDSA and SePTX, π-π interactions between SeDSA molecules and hydrophobic interactions between SePTX molecules. Meanwhile, Se-Se bonds play a crucial role in balancing the intramolecular forces. These diselenide-containing nanoparticles (SeDSA NPs, SePTX NPs and Co-NPs) exhibit a high stability under physiological conditions and excellent reduction-sensitivity in the presence of the redox agent glutathione (GSH) because of the selenium-sulfur exchange reaction between diselenide and GSH. Both SeDSA NPs and Co-NPs show strong orange fluorescence emissions on the account of the AIE feature of SeDSA and they were easily internalized by HeLa and HepG2 cells. Distinctively, the Co-NPs combine the advantage of SeDSA and SePTX for cell imaging and antineoplastic activity, and exhibit selectivity of cytotoxicities between neoplasia cells and normal cells. This study highlights the development of diselenide-containing AIEgens as a unique approach to prepare uniform and stable fluorescent nanoparticles for the application in cell imaging and tumor treatment.

Local tumor photothermal treatment with the near-infrared light at the second window (NIR-II) is a promising strategy in triggering the in situ tumor vaccination (ISTV) for cancer therapy. However, limited penetration of photothermal agents within tumors seriously limits their spatial effect in generating sufficient tumor-associated antigens, a key factor to the success of ISTV. In this study, a nano-adjuvant system is fabricated based on the NIR-II-absorbable gold nanostars decorated with hyaluronidases and immunostimulatory oligodeoxynucleotides CpG for ISTV. The nano-adjuvant displays a deep tumor penetration capacity via loosening the dense extracellular matrix of tumors. Upon NIR-II light irradiation, the nano-adjuvant significantly inhibits the tumor growth, induces a cascade of immune responses, generates an obvious adaptive immunity against the re-challenged cancers, boosts the abscopal effect, and completely inhibits the pulmonary metastases. The study highlights an advanced nano-adjuvant formulation featuring deep tumor penetration for NIR-II-triggered ISTV.

The development of robust photothermal agents for near-infrared (NIR) imaging is a great challenge. Herein, we report the design and synthesis of a new photothermal agent, based on the aza-boron-dipyrromethene framework (azaBDP). This compound possessed excellent photostability and high photothermal-conversion efficiency (50 %) under NIR laser irradiation. When the photothermal properties of this compound were utilized for tumor inhibition, stable long-term fluorescence was observed in living animals. Photothermal treatment efficiently suppressed tumor growth, as evidenced by in vitro and in vivo experiments. Furthermore, NIR emission could be detected by using an imaging system and therapeutic self-monitoring was achieved by using NIR imaging.

Compared to traditional clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system, CRISPR/dead Cas9 (dCas9) system can precisely regulate endogenous gene expression without damaging the host gene, representing a greater potential for cancer therapy. Cancer/testis antigen 45 (CT45) is proved to enhance platinum-based chemosensitivity for individualized ovarian cancer therapy. However, the development of a single nanocarrier codelivering CRISPR/dCas9 system and chemotherapeutics for synergistic cancer therapy still faces challenges. Herein, a reduction-sensitive fluorinated-Pt(IV) universal transfection nanoplatform (PtUTP-F) is developed for the CT45-targeted CRISPR/dCas9 activation to achieve synergistic and individualized treatment of ovarian cancer. Overcoming multiple physiological barriers, PtUTP-F condensed gene can efficiently transfect into different cells including 293T cells, A2780, SKOV3, A549, and A2780/cisplatin (DDP) cancer cells, which is superior to Lipofectamine 6000. With the responsive release of gene and Pt(II) in the intracellular reducing microenvironment, PtUTP-F/dCas9-CT45 can generate CRISPR/dCas9 activation of CT45 expression for protein phosphatase 4C (PP4C) activity inhibition to hinder the DNA repair pathway and thus enhances the sensitivity to Pt(II) drugs for individualized A2780 tumor therapy. The PtUTP-F not only represents a powerful nanoplatform for CRISPR/dCas9 system delivery but also initiates a novel strategy for synergistic and individualized treatment of CRISPR/dCas9-based gene therapy with chemotherapy.

The increasing resistance risks of conventional antibiotic abuse and the formed biofilm on the surface of wounds have been demonstrated to be the main problems for bacteria-caused infections and unsuccessful wound healing. Treatment by reactive oxygen species, such as the commercial H2 O2 , is a feasible way to solve those problems, but limits in its lower efficiency. Herein, an ionic covalent-organic framework-based nanozyme (GFeF) with self-promoting antibacterial effect and good biocompatibility has been developed as glucose-triggered cascade catalyst against bacterial wound infection. Besides the efficient conversion of glucose to hydrogen peroxide, the produced gluconic acid by loading glucose oxidase can supply a compatible catalytic environment to substantially improve the peroxidase activity for generating more toxic hydroxyl radicals. Meanwhile, the adhesion between the positively charged GFeF and the bacterial membrane can greatly enhance the healing effects. This glucose-triggered cascade strategy can reduce the harmful side effects by indirectly producing H2 O2 , potentially used in the wound healing of diabetic patients.

Polymer-modified metal-organic frameworks combine the advantages of both soft polymers and crystalline metal-organic frameworks (MOFs). It is a big challenge to develop simple methods for surface modification of MOFs. In this work, MOF@microporous organic polymer (MOP) hybrid nanoparticles (UNP) have been synthesized by epitaxial growth of luminescent boron-dipyrromethene (BODIPYs)-imine MOPs on the surface of UiO-MOF seeds, which exhibit low cytotoxicity, smaller size distribution, well-retained pore integrity, and available functional sites. After folic acid grafting, the enhanced intracellular uptake and bioimaging was validated.

Inborn errors of metabolism occur with high incidence in human populations, and inborn deficiencies in fatty acid b-oxidation (FAO) are clinically associated with neurological deficits such as speech weakness, motor delay, and autism. Using in vivo assays for analyzing neural stem cells (NSCs) in the developing mammalian forebrain, we find that neural stem cell (NSC)-autonomous deficiencies in long-chain FAO deplete neural stem cell (NSC) pools from mouse embryonic neocortex. Acute interference with activity of TMLHE (catalyzes the first step in carnitine biosynthesis), or with CPT1A (the rate-limiting enzyme for carnitine-dependent transport of long-chain fatty acids into mitochondria), results in impaired NSC self-renewal. Moreover, dorsal forebrain-specific eviction of the Cpt1a gene resulted in reduced thickness of the murine neocortex at birth. Importantly, NSC deficits induced by TMLHE insufficiencies are rescued by exogenous carnitine in both cultured explants and by supplementation of the maternal...

Rational selection and modification of rare earth metal centers and photoactive organic linkers enables designable multiphotofunctionality to come to fruition in new hybrid coordination polymer materials. By using a viologen-functionalized diphosphonate linker, two terbium phosphonate compounds (Tb-1 and Tb-2) have been constructed, which display reversible photochromic reactions in response to UV light and soft X-ray irradiation. In addition, the photo-induced electron-transfer reaction can modulate the luminescent emission to thus realize photoluminescence switching behavior. Furthermore, both terbium phosphonates can serve as highly sensitive sensors to probe Cu2+ in solution through their luminescence. Thus, they represent the first photochromic examples of lanthanide phosphonate-based materials with photomodulated luminescence and sensitive detection of metal ions.

A UiO-66 core with various sizes acts as heterogeneous nucleation center and enables aniline polymerization under ambient conditions. The as-synthesized UiO-66@PAN possesses uniform size and excellent dispersibility in aqueous solution. UiO-66@PAN can be internalized by cancer cells via endocytosis, and indicates significant photothermal therapeutic effect in vitro, and can effectively inhibit the growth of colon cancers in vivo.

Development of an innovative nucleic acid nanocarriers still represents a challenge. In this study, we develop a protein nanoparticle (H6-TatEGFP) and examine its siRNA condensing activity. Gel retardation assay show that protein nanoparticle can condense siRNA into stable nanoparticle/siRNA complexes. UsingCy3-labelled siRNA, we also evaluate siRNA transport characteristic of protein nanoparticles in tumor cells, the results indicate that H6-TatEGFP nanoparticle may be a potential nanocarrier for siRNA in tumor cells.

The protein adsorption and self-assembly behavior of biocompatible graft copolymer, poly(lactide-co-diazidomethyl trimethylene carbonate)-g-poly(ethylene glycol) [P(LA-co-DAC)-g-PEG], were systematically studied. The graft copolymers showed enhanced resistance to non-specific protein adsorption compared with their block copolymer counterparts, indicative of the increased effect of PEG density beyond PEG length. Diverse nanostructures including vesicles can be assembled from the amphiphilic graft copolymers with well-defined nano-sizes. Hemoglobin (Hb), as a model protein, can be entrapped in the formed vesicles and keep the gas-binding capacity. The reduced release rate of Hb from graft copolymer vesicles indicated the relatively stable membrane packing compared with block copolymer counterpart.

A facile solvothermal route to synthesize S,N co-doped graphene quantum dots (S,N-GQDs) with unique optical properties is demonstrated. Three absorption bands are observed at 338, 467, and 557 nm, which is different from any previous reports. The photoluminescent spectra display emissions in three primary colors that are independent of the excitation wavelength, within the excitation wavelength ranges of 340–420 nm, 460–540 nm, and 560–620 nm. The PL excitation spectra indicate that each emission is related to a single excitation band. It is proposed that three independent luminescent centers coexist in S,N-GQDs because the doping with S and N may change the chemical environment of the GQDs. However, energy-transfer processes usually do not occur among the independent luminescent centers under different wavelength light excitation. Heteroatom-doping of GQDs provides an attractive means of effectively tuning their optical properties for the purpose of exploiting new applications in visible-light photocatalytic and bioimaging. S,N-GQDs/TiO2 composites exhibit better hydrogen production activities under visible light (λ > 420 nm) than commercial TiO2 (P25), owing to the presence of characteristic absorption bands in the visible region. Furthermore, the S,N-GQDs have a pronounced biocompatibility and bioimaging ability under long-wavelengths excitation for live A549 cells.

A theranostic nanomedicine (CD-Oxa) is synthesized by means of the condensation reaction between the amino groups on the surface of fluorescent carbon dots (CDs) and the carboxyl group of the oxaliplatin derivative Oxa(IV)-COOH. CD-Oxa, which integrates the optical properties of CDs and the anticancer function of oxaliplatin, could be used for simultaneous drug delivery and fluorescent tracking.

The singlet oxygen (1O2) generation ability of a photosensitizer (PS) is pivotal for photodynamic therapy (PDT). Transition metal complexes are effective PSs, owing to their high 1O2 generation ability. However, non‐negligible cellular toxicity, poor biocompatibility, and easy aggregation in water limit their biomedical applications. In this work, a series of red‐emitting aggregation‐induced emission (AIE) Ir(III) complexes containing different numbers of Ir centers (mono‐, di‐, and trinuclear) and the corresponding nanoparticles (NPs) AIE‐NPs, are designed and synthesized. The increase of 1O2 generation ability is in line with the increasing number of Ir centers. Compared with the pure Ir(III) complexes, the corresponding NPs offer multiple advantages: (i) brighter emission; (ii) higher phosphorescence quantum yields; (iii) longer excited lifetime; (iv) higher 1O2 generation ability; (v) better biocompatibility; and (vi) superior cellular uptake. Both in vitro and in vivo experiments corroborate that AIE‐NPs with three iridium centers possess potent cytotoxicity toward cancer cells and effective inhibition of tumor growth. To the best of knowledge, this work is the first example of NPs of multinuclear AIE Ir(III) complexes as PSs for enhanced PDT. This study offers a new method to improve the efficiency of PSs for clinical cancer treatments.

A Pt (IV) complex which combined the bioactivities of both oxaliplatin and demethylcantharidin (DMC) is synthesized and delivered by a polymer-drug conjugate for combination chemotherapy. Oxaliplatin is released from the polymer-drug conjugate within cancer cell by reduction to attack nuclear DNA, while a dose of DMC is also hydrolyzed subsequently to block DNA damage-induced defense mechanisms by serine/threonine phosphatase 2A (PP2A) inhibition. In vitro evaluation shows that the polymer-drug conjugate with dual modes of action upon cancer cells displays higher cytotoxicity against SKOV-3 cells than that of free drugs. This enhanced cytotoxicity is attributed to the synergistic effect between oxaliplatin and DMC, as well as the effective intracellular internalization of the micelles observed by confocal laser scanning microscopy (CLSM) imaging.

A photo-cross-linked micelle is synthesized via photodimerization of thymine moieties fabricated from amphiphilic block copolymers (mPEG-b-P(LA-co-MPT). The crosslinking behavior is monitored by UV-Vis spectra and H-1 NMR. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that cross-linked micelles had smaller sizes than their uncross-linked precursors. In vitro studies reveal that cross-linking of the micelle cores results in a slow drug release and faster cellular uptake in comparison with uncross-linked ones in MCF-7 and Hela cells. Moreover, the paclitaxel (PTX)-loaded core-cross-linked micelles exhibit similar anticancer efficacy as free PTX. This work provides a convenient tool for designing a more stable structure in the blood circulation to realize a controlled drug delivery.

Amphiphilic triblock copolymers with carbonyl groups located either in the middle segment or in the third side block are synthesized by adjusting feeding sequence of the comonomers. The conjugation of hemoglobin (Hb) on the copolymer micelles is realized by condensation reactions of carbonyl with the amino groups of Hb, and the gas-binding capacity of Hb is well preserved. Interestingly, the reassembly behavior of Hb-conjugated micelles (HbM) is explored by adjusting the pH. As for triblock copolymers with a carbonyl-functionalized segment as the third block, Hb is rearranged into the inner core of micelles when the pH is adjusted close to the isoelectric point of Hb. Therefore, it may provide a new needed route for fabrication of protein carriers, which is different from the traditional encapsulation technique.

Multifunctional hybrid micelles are prepared from amphiphilic mal-PEG-b-PLA and mPEG-b-P(LA-co-DHC/RhB) block copolymers. A specific anti-transferrin receptor antibody, OX26, is linked onto the surface of the micelles. ELISA indicates that the conjugated antibody preserves its activity. OX26 conjugation can increase the uptake efficiency of micelles by target cell lines (C6). Pharmacokinetics and in vivo biodistribution experiments are carried out to investigate the ability of OX26-conjugated micelles (immunomicelles) to cross the bloodbrain barrier. The data show that the brain uptake of OX26-conjugated micelles is much more than that of OX26-free ones. Therefore, OX26-conjugated micelles will be promising drug carriers to cross the blood-brain barrier.

Biodiesel (BD) is a renewable fuel for compression ignition engines that is composed of the simple alkyl esters, usually methyl-, of fatty acids (FAME). It is typically produced via base-catalyzed transesterification between refined vegetable oil or animal fat (e.g., soybean oil, tallow) and an alcohol (e.g., methanol). This process can, however, be marginally cost-effective due to the high feedstock and processing costs. It is thus desirable to develop new catalytic routes that can efficiently convert less expensive feedstocks to BD. We report here on the application of a series of diarylammonium based homogeneous and heterogeneous catalysts for converting a particularly low value, low quality lipid, trap grease, to FAME. In the course of a 1-h reaction at 125 °C these catalysts simultaneously esterified the free fatty acids (>90 wt% of the substrate) and transesterified the acylglycerols (

The compensatory growth response of juvenile three-keeled pond turtles, Chinemys reevesii, was investigated by food deprivation for 1–4 wk and then refeeding for 4 wk. After feeding resumed, only turtles that were deprived over 2 wk displayed higher specific growth rates than the continuously fed turtles for 1 wk, but their weights were lower than the control at the end of refeeding, showing a partial compensatory growth pattern. Their feeding rate, rather than the feed conversion efficiency and apparent digestibility of energy, was higher than the control during the compensatory phase, indicating that hyperphagia was responsible for the compensatory growth. As starvation intensified, protein concentrations of deprived turtles increased significantly, whereas the contents of fat tissues decreased sharply. After 4 wk of refeeding, the contents of fat tissues in deprived turtles returned to the control level, whereas protein concentrations did not, indicating that lipid rather than protein was the main fuel utilized during short-term starvation for juvenile turtles aged over 2 mo.

We report a new in situ tissue slide-based SELEX strategy targeting neoplastic tissues from breast cancer patients. The methodology, using the molecular differences between clinical specimens, can evolve aptamers to all fractions of tissue. The aptamers may be used as new molecular probes for pathological diagnosis and tumour imaging, and also to reveal the molecular differences that are responsible for the diseases. The specific aptamers were enriched by unequal length strand PCR employing a structured (−) strand primer. After 12 rounds of selection, using the paraffin tissue sections from infiltrating ductal carcinomas as targets, and using the adjacent normal tissue from the same case as controls, one of the enriched ssDNA aptamers, BC15, was selected from a nucleic acid library and characterized as recognizing breast cancer cells either within the tissue sections or from the culture medium, but only weakly binding to adjacent normal cells or immortalized breast cell line MCF10A. The calculated equilibrium dissociation constants (Kd) of BC15 bound to MCF7 cells was 111.0 ± 36.9 nM. Through streptavidin magnetic beads mediated affinity purification assay followed by mass spectrometry identification and western blot confirmation, the target of BC15 was characterized to be hnRNP A1, which was further verified to be specifically and highly expressed in cancerous tissues of breast by hnRNP A1 antibody immunostaining as well as western blot. BC15 aptamer was also used to probe cancer cells in tissues from other pathological types of breast cancers including lobular carcinoma, ductal carcinoma complicated with lobular carcinoma, comedo carcinoma, and lymph node metastasis of breast ductal carcinoma origin or breast lobular carcinoma origin. Therefore, tissue slide-based SELEX holds promise in identifying tumour markers and developing specific molecular probes for cancer diagnosis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A facile approach to the preparation of light-responsive copolymer micelles is developed. This approach is based on the attachment of hydrophobic groups to one block of a diblock copolymer via a light-sensitive linkage. The micelles can be dissociated under light irradiation and release the encapsulated pyrene. The obtained polymeric micelles are expected to be of use as drug-delivery vehicles.

A diblcok copolymer monomethoxy poly (ethylene glycol)-block-poly(L-lactide-co-2-methyl-2-carboxyl-propylene carbonate) (MPEG-b-P(LA-co-MCC)) was obtained by copolymerization of L-lactide (LA) and 2-methyl-2-benzoxycarbonyl-propylene carbonate (MBC) and subsequent catalytic hydrogenation. The pendant carboxyl groups of the copolymer MPEG-b-P(LA-co-MCC) were conjugated with antitumor drug docetaxel and tripeptide arginine-glycine-aspartic acid (RGD), respectively.

This article deals with (1) synthesis of novel cyclic carbonate monomer (2-oxo [1,3]dioxan-5-yl)carbamic acid benzyl ester (CAB) containing protected amino groups; (2) ring-opening copolymerization of the cyclic monomer with L-lactide (LA) to provide novel degradable poly(ester-carbonate)s with functional groups; (3) removal of the protective benzyloxycarbonyl (Cbz) groups by catalytic hydrogenation to afford the corresponding poly(ester-co-carbonate)s with free amino groups; (4) grafting of oligopeptide Gly-Arg-Gly-Asp-Ser-Tyr (GRGDSY, abbreviated as RGD) onto the copolymer pendant amino groups in the presence of 1,1'-carbonyldiimidazole (CDI).

The synthesis of a new cyclic carbonate monomer containing an allyl group was reported and its biodegradable amphiphilic block copolymer, poly(ethylene glycol)-block-poly(L-lactide-co-5-methyl-5-allyloxycarbonyl-propylene carbonate) [PEG-b-P(LA-co-MAC)] was synthesized by ring-opening polymerization (ROP) of L-lactide (LA) and 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) in the presence of poly (ethylene glycol) as a macroinitiator, with diethyl zinc as a catalyst. 13 C NMR and 1 H NMR were used for microstructure identification of the copolymers. The copolymer could form micelles in aqueous solution. The core of the micelles is built of the hydrophobic P(LA-co-MAC) chains, whereas the shell is set up by the hydrophilic PEG blocks. The micelles exhibited a homogeneous spherical morphology and unimodal size distribution. By using the cyclic carbonate monomer containing allyl side-groups, crosslinking of the PEG-b-P(LA-co-MAC) inner core was possible. The adhesion and spreading of ECV-304 cells on the copolymer were better than that on PLA films. Therefore, this biodegradable amphiphilic block copolymer is expected to be used as a biomaterial for drug delivery and tissue engineering.

A novel biodegradable aliphatic poly(L-lactide-co-carbonate) bearing pendant acetylene groups was successfully prepared by ring-opening copolymerization of L-lactide (LA) with 5-methyl-5-propargyloxycarbonyl-1,3-dioxan-2-one (PC) in the presence of benzyl alcohol as initiator with ZnEt2 as catalyst in bulk at 100 degrees C and subsequently used for grafting 2-azidoethyl beta-D-glucopyranoside and 2-azidoethyl beta-lactoside by the typical "click reaction," that is Cu(I)-catalyzed cycloaddition of azide and alkyne. The density of acetylene groups in the copolymer can be tailored by the molar ratio of PC to LA during the copolymerization. The aliphatic copolymers grafted with sugars showed low cytotoxicity to L929 cells, improved hydrophilic properties and specific recognition and binding ability with lectins, that is Concanavalin A (Con A) and Ricinus communis agglutinin (RCA). Therefore, this kind of sugar-grafted copolymer could be a good candidate in variety of biomedical applications.

Novel poly(ester carbonate)s were synthesized by the ring-opening polymerization Of L-lactide and functionalized carbonate monomer 9-phenyl-2,4,8,10-tetraoxaspiro[5,5]undecan-3-one derived from pentaerythritol with diethyl zinc as an initiator. H-1 NMR analysis revealed that the carbonate content in the copolymer was almost equal to that in the feed. DSC results indicated that T-g of the copolymer increased with increasing carbonate content in the copolymer. Moreover, the protecting benzylidene groups in the copolymer poly(L-lactide-co-9-phenyl-2,4,8,10-tetraoxaspiro[5,5]undecan-3-one) were removed by hydrogenation with palladium hydroxide on activated charcoal as a catalyst to give a functional copolymer, poly(L-lactide-co-2,2-dihydroxylmethyl-propylene carbonate), containing pendant primary hydroxyl groups. Complete deprotection was confirmed by H-1 NMR and FTIR spectroscopy. The in vitro degradation rate of the deprotected copolymers was faster than that of the protected copolymers in the presence of proteinase K. The cell morphology and viability on a copolymer film evaluated with ECV-304 cells showed that poly(ester carbonate)s derived from pentaerythritol are good biocompatible materials suitable for biomedical applications.

A triblock poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid) (PLA-PEG-PLA)/paclitaxel (PTX) conjugate was synthesized by the reaction of carboxyl-terminated copolymer PLA-PEG-PLA with PTX in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. Carboxyl-terminated copolymer PLA-PEG-PLA was prepared by the reaction of the hydroxyl end groups in copolymer PLA-PEG-PLA with succinic anhydride. Its structure was confirmed by NMR and gel permeation chromatography. The PLA-PEG-PLA/PTX conjugates could self-assemble into micelles in aqueous solutions with a low critical micelle concentration. Dynamic light scattering and environmental scanning electron microscopy analyses of the PLA-PEG-PLA/PTX micelles revealed their spherical structure and size of 220 nm. The antitumor activity of the conjugate against woman Hela cancer cells, evaluated by the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl tetrazolium bromide method, showed that the conjugates had an antitumor activity similar to that of pure PTX. The obtained PLA-PEG-PLA/PTX conjugates are expected to be used in clinical practice.

An amphiphilic block copolymer, poly(ethylene glycol)-block-poly(L-lactide-co-2-methyl-2-benzoxycarbonyl-propylene carbonate) [PEG-b-P(LA-co-MBC)], was synthesized in bulk by the ring-opening polymerization of L-lactide with 2-methyl-2-benzoxycarbonyl-propylene carbonate (MBC) in the presence of poly(ethylene glycol) as a macroinitiator with diethyl zinc as a catalyst. The subsequent catalytic hydrogenation of PEG-b-P(LA-co-MBC) with palladium hydroxide on activated charcoal (20%) as a catalyst was carried out to obtain the corresponding linear copolymer poly(ethyleneglycol)-block-poly(L-lactide-co-2-methyl-2-carboxyl-propylenecarbonate) [PEG-b-P(LA-co-MCC)] with pendant carboxyl groups. DSC analysis indicated that the glass-transition temperature (Tg) of PEG-b-P(LA-co-MBC) decreased with increasing MBC content in the copolymer, and Tg of PEG-b-P(LA-co-MCC) was higher than that of the corresponding PEG-b-P(LA-co-MBC). The in vitro degradation rate of PEG-b-P(LA-co-MCC) in the presence of proteinase K was faster than that of PEG-b-P(LA-co-MBC), and the cytotoxicity of PEG-b-P(LA-co-MCC) to chondrocytes from human fetal arthrosis was lower than that of poly(L-lactide). © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4771–4780, 2005

Combination therapy of paclitaxel (PTX) and cisplatin has been used to treat several cancers in clinic practice, but often causes serious systemic toxicity. Co-delivery of PTX and cisplatin by means of polymeric micelles can reduce the systemic toxicity, but often needs two carrier polymers because of the solubility difference between them. Therefore, a strategy is developed to co- deliver both PTX and cisplatin with only one carrier polymer by encapsulating PTX in the core of a polymeric micelle and cross- linking the micelle with cisplatin. The PTX and Pt contents in the micellar formulation M(PTX/Pt) were 10 and 14 wt %, respec- tively. In vitro cytotoxicity of M(PTX/Pt) was evaluated via 3-(4,5-dimethylthiazol-2-yl)22,5-diphenyltetrazolium bromide assay in comparison with PTX and its micelle M(PTX), cisplatin and its micelle M(Pt), and PTX/cisplatin combination towards human hepa- tocarcinoma (SMMC-7721) cells and chemoresistant SMMC-7721(SMMC-7721R) cells. The M(PTX/Pt) exhibited a high synergistic effect in the inhibition of cell growth and proliferation of both SMMC-7721 and SMMC-7721R cells and showed reasonable drug- resistance relief. The synergistic effect and resistance relief were further supported or explained by intracellular uptake measurement of dye-labeled micelles and by the confocal laser scanning microscopy observation of SMMC-7721 and SMMC-7721R cells treated with various formulations. Therefore, M(PTX/Pt) micelles were expected to find potential application in cancer chemotherapy. V C 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41440.

Cisplatin was incorporated into polymeric carriers through the coordination of pt with the carboxylic groups of methoxypoly( ethylene glycol) (mpeg)-block-poly[(2-carboxy-ethylsulfanyl)-propyl glycidyl ether] (pcpge). the mpeg-b-pcpge/pt complexes with a pt content of 14 wt % could self-assemble into spheric micelles with diameter of about 80 nm in aqueous solution. the effective internalization of the polymer platinum micelles by the cells via an endocytosis mechanism was confirmed by confocal laser scanning microscopy and flow cytometry. the antitumor activity of the polymeric micelles was similar to that of cisplatin in vitro. the in vivo blood clearance of platinum was studied, and the results show that the micelles exhibited longer blood circulation than the free cisplatin. the biodistribution of cisplatin and its micelles in mice was studied through the measurement of the pt content in plasma, organs, and tumors, especially in tumor cell dna. their antitumor activity in vivo, assessed in mice bearing h22 liver cancers, showed that the micelles exhibited greater antitumor efficacy than free cisplatin. therefore, this polymer platinum micelle is a promising candidate as a smart antitumor drug carrier for malignancy therapy in future clinical applications. (c) 2014 wiley periodicals, inc.

A series of four-arm star block copolymers poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-PDLLA) with different hydrophobic length were synthesized by ring-opening polymerization of lactide and characterized using H-1 NMR and gel permeation chromatography (GPC). These copolymers could self-assemble in aqueous solution to form the vesicle structure with controlled size and morphologies. Transmission electron microscopy (TEM) and DLS show the polymersomes are spherical with diameter of 70 approximate to 500 nm. The polymersomes made by direct hydration of copolymer thin films in water exhibit the controllable ability of encapsulating hemoglobin under mild condition. The hemoglobin content in the polymersomes could reach to 35 wt %. More importantly, the encapsulated hemoglobin keeps its own bioactivity and is capable of binding oxygen. This hemoglobin-encapsulated four-arm PEG-PLA polymersomes could have the potential to be applied as an artificial oxygen carrier for transfusion. (c) 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40433.

Herein, a kind of dual acid-sensitive nanoparticles based on monomethoxy poly(ethylene glycol)-imine-β-cyclodextrin is constructed by a facile phenylboronic acid-cross-linked way. The data of dynamic light scattering and transmission electron microscope reveal the cross-linked nanoparticles have improved stability. The cross-linked nanoparticles could easily self-assemble and load the anticancer drug at neutral pH condition. However, when the drug-loaded nanoparticles are delivered to extracellular tumor sites (pH ≈6.8), the surface of the nanoparticles would be amino positively charged and easily internalized by tumor cell due to the cleavage of the acid-labile benzoic-imine. Subsequently, with the acidity in subcellular compartments significantly increasing (such as the endosome pH ≈5.3), the loaded drug would fast release from the endocytosis carriers due to the hydrolysis of boronate ester. These features suggest that these dual acid-sensitive cross-linked nanoparticles not only possess excellent biocompatibility but also can efficiently load and deliver anticancer drug into tumor cells to enhance the inhibition of cellular proliferation, outlining a favorable platform as drug carriers.