[Research progress on physical activity of childhood cancer survivors].

Many childhood cancer survivors are suffering serious and long-lasting complications or sequelae, taking a significant toll on their health. Adequate physical activity can be effective in mitigating the negative effects of these complications or sequelae. However, low levels of physical activity are prevalent among childhood cancer survivors. Due to the lack of guidelines on physical activity for childhood cancer survivors, there are many difficulties in correctly guiding childhood cancer survivors to participate in physical activity. Therefore, it is necessary to summarize the relevant studies on the physical activity of childhood cancer survivors. This article provides a review of the concept and measurement of physical activity, recommended amount, and the participation of childhood cancer survivors both domestically and internationally, in order to provide a reference for promoting the physical activity level of Chinese childhood cancer survivors.

Improved light extraction efficiency of AlGaN deep-ultraviolet light emitting diodes combining Ag-nanodots/Al reflective electrode with highly transparent p-type layer.

Enhancement of light extraction efficiency (LEE) of AlGaN-based deep-ultraviolet (DUV) light emitting diodes (LEDs) has been attempted by adopting Ag-nanodots/Al reflective electrodes on a highly transparent complex p-type layer. By thinning the p-GaN to several nm, highly DUV transparent p-type layer is achieved, making it meaningful for the application of reflective electrodes composed of Ag-nanodots and Al film to allow most light emitted upward to be reflected back to the sapphire side. By this approach, the maximum light output power and external quantum efficiency of the DUV-LEDs with optimized Ag nanodots/Al electrodes are severally increased by 52% and 58%, respectively, compared to those with traditional Ni/Au electrodes when the current is below 200 mA.

Anisotropic dependence of light extraction behavior on propagation path in AlGaN-based deep-ultraviolet light-emitting diodes.

The anisotropic extraction dependence of polarized light on propagation path in AlGaN-based deep-ultraviolet (DUV) light-emitting diodes (LEDs) is investigated by simulations and photoluminescence (PL) measurements. Theoretical calculations based on k⋅p approximation and Monte Carol ray tracing indicate that there are two kinds of polarized sources with different angular distributions in ~280 nm AlGaN-based LEDs, s-polarized (spherical-shaped) and p-polarized (dumbbell-shaped) sources, which have different extraction behaviors. It is found that the total light extraction intensities are improved with decreasing the propagation path, and the lateral surface extraction gradually becomes dominant. Moreover, the extraction intensity of s-polarized light improves more than that of p-polarized light when the propagation path decreases, leading to a greater polarization degree. Polarization-resolved PL measurements show that the polarization degree of extracted light from lateral facet of the AlGaN multiple quantum well sample can be enhanced from 1% to 17% as the average propagation path reduces by 0.6 mm, which is consistent with the simulation results of the anisotropic dependence of light extraction on propagation path. Our results are significant for understanding and modulating the anisotropic extraction behavior of polarized light to realize high efficiency AlGaN-based DUV LEDs.

Greatly enhanced performance of AlGaN-based deep ultraviolet light emitting diodes by introducing a polarization modulated electron blocking layer.

Carrier transport in AlGaN-based deep ultraviolet (DUV) light emitting diodes (LEDs) with the wavelength of 273 nm has been investigated by introducing polarization modulated electron blocking layer (EBL) that adopts an Al composition and thickness graded multiple quantum barriers (MQB) structure. The experimental result shows that the maximum light output power and external quantum efficiency for the proposed structure at the current of 250 mA are 9.6 mW and 1.03% respectively, severally increasing by 405% and 249% compared to traditional one, meanwhile, the efficiency droop at 250 mA is also dramatically reduced from 42.2% to 16.6%. Further simulation analysis indicates that this graded MQB-EBL enhances the potential barrier height for electrons and meanwhile reduces that for holes, hence effectively suppresses the electron leakage, and at the same time significantly improves the hole injection efficiency. As a result, the whole performance of the LED with the proposed MQB-EBL is dramatically improved.

Bioreducible comb-shaped conjugates composed of secondary amine and hydroxyl group-containing backbones and disulfide-linked side chains with tertiary amine groups for facilitating gene delivery.

Comb-shaped polymeric vectors (SS-PGEADMs) consisting of ethanolamine/cystamine-functionalized poly(glycidyl methacrylate) (SS-PGEA-NH2) backbones and bioreducible poly((2-dimethyl amino)ethyl methacrylate) (PDMEAMA) side chains were prepared by a combination of the ring-opening reaction and atom transfer radical polymerization (ATRP). The SS-PGEA-NH2 backbones, which were prepared via the ring-opening reaction of the pendant epoxide groups of poly(glycidyl methacrylate) with the amine moieties of ethanolamine/cystamine, possess plentiful flanking secondary amine and hydroxyl groups and some flanking disulfide bond-containing cystamine derivatives. The primary amine groups of the cystamine derivatives were activated to produce bromoisobutylryl-terminated SS-PGEA (SS-PGEA-Br) as multifunctional initiators for subsequent ATRP of DMAEMA. The resultant disulfide-linked short PDMEAMA side chains possess pendant tertiary amine groups and are biocleavable. Such SS-PGEADMs can effectively condense pDNA. The cytotoxicity of SS-PGEADMs could be controlled by adjusting the grafting amount of PDMEAMA side chains. In comparison with the pristine SS-PGEA-NH2, the moderate introduction of PDMEAMA side chains can further enhance the gene transfection efficiency in different cell lines. The present approach to well-defined comb-shaped vectors with multifunctional groups could provide a versatile means for tailoring the functional structures of advanced gene/drug vectors.

Supramolecular host-guest pseudocomb conjugates composed of multiple star polycations tied tunably with a linear polycation backbone for gene transfection.

A series of novel supramolecular pseudocomb polycations (l-PGEA-Ad/CD-PGEAs) were synthesized by tying multiple low-molecular-weight ß-cyclodextrin (CD)-cored, ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) star polymers (CD-PGEAs) with an adamantine-modified linear PGEA (l-PGEA-Ad) backbone via the host-guest interaction. The pseudocomb carriers were studied in terms of their DNA binding capabilities, cytotoxicities, and gene transfection efficiencies in the HepG2 and HEK293 cell lines. The pseudocomb l-PGEA-Ad/CD-PGEAs exhibited better plasmid DNA-condensing abilities than their counterparts, CD-PGEA and l-PGEA. Meanwhile, the pseudocomb carriers displayed low cytotoxicity, similar to CD-PGEA and l-PGEA. Moreover, the gene transfection efficiencies of the pseudocomb carriers were much higher than those of CD-PGEA and l-PGEA at various PGEA nitrogen/DNA phosphate molar ratios. Such supramolecular preparation of pseudocomb gene carriers could provide a flexible approach for adjusting the structure and functionality of supramolecular polymers via the proper use of non-covalent interactions.

Functionalized layered double hydroxide nanoparticles conjugated with disulfide-linked polycation brushes for advanced gene delivery.

Layered double hydroxides (LDHs) have aroused great attention as potential nanosized drug delivery carriers, but independent inorganic LDH wrapped with DNA shows very low transfection efficiency. To manipulate and control the surface properties of LDH nanoparticles is of crucial importance in the designing of LDH-based drug carriers. In this work, surface-initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DMAEMA) is employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined novel gene delivery vectors (termed as LDH-PDs), where a flexible three-step method was first developed to introduce the ATRP initiation sites containing disulfide bonds onto LDH surfaces. In comparison the pristine LDH particles, the resultant LDH-PDs exhibited better ability to condense plasmid DNA (pDNA) and much higher levels to delivery genes in different cell lines including COS7 and HepG2 cell lines. Moreover, the LDH-PDs also could largely enhance cellular uptake. This present study demonstrates that functionalization of bioinorganic LDH with flexible polycation brushes is an effective means to produce new LDH-based gene delivery systems.

Simple strategy to functionalize polymeric substrates via surface-initiated ATRP for biomedical applications.

The functionalization of polymer surfaces via surface-initiated atom transfer radical polymerization (ATRP) is of crucial importance to prepare various functional materials. It is generally complicated to conduct ATRP on different organic material surfaces. In this work, a facile photoinduced one-step method was first developed for the covalent immobilization of ATRP initiators on the C-H group-containing substrates such as biaxially oriented polypropylene (BOPP). The C-H bonds of precise location of inert polymer surfaces were readily transferred to bromoalkyl initiator, followed by ATRP of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and glycidyl methacrylate (GMA), respectively, to produce the resultant patterned BOPP-g-P(DMAEMA) and BOPP-g-P(GMA) films. The epoxy groups of the P(GMA) microdomains can be aminated for covalently coupling IgG, while the P(DMAEMA) microdomains were used for immobilizing IgG via electronic interactions. The resultant IgG-coupled microdomains could interact with the corresponding target proteins, anti-IgG.

Facilitation of gene transfection with well-defined degradable comb-shaped poly(glycidyl methacrylate) derivative vectors.

Recently, we reported that ethanolamine (EA)-functionalized poly(glycidyl methacrylate) (PGMA) vectors (PGEAs) can produce good transfection efficiency, while exhibiting very low toxicity. Further improvement in degradability and transfection efficiency of the PGEA vectors will facilitate their application in gene therapy. Comb-shaped cationic copolymers have been of interest and importance as nonviral gene carriers. Herein, the degradable high-molecular-weight comb-shaped PGEA vectors (c-PGEAs) composed of the low-molecular-weight PGEA backbone and side chains were prepared by a combination of atom transfer radical polymerization (ATRP) and ring-opening reactions. The PGEA side chains were linked with the PGEA backbones via hydrolyzable ester bonds. Such comb-shaped c-PGEA vectors possessed the degradability, good pDNA condensation ability, low cytotoxicity, and good buffering capacity. More importantly, the comb-shaped c-PGEA vectors could enhance the gene expression levels. Moreover, the PGEA side chains of c-PGEA could also be copolymerized with some poly(poly(ethylene glycol)ethyl ether methacrylate) species to further improve the gene delivery system.

PCL film surfaces conjugated with P(DMAEMA)/gelatin complexes for improving cell immobilization and gene transfection.

Successful gene transfection on a tissue scaffold is of crucial importance in facilitating tissue repair and regeneration by enabling the localized production of therapeutic drugs. Polycaprolactone (PCL) has been widely adopted as a scaffold biomaterial, but its unfavorable cell-adhesion property needs to be improved. In this work, the PCL film surface was conjugated with poly((2-dimethyl amino)ethyl methacrylate) (P(DMAEMA))/gelatin complexes via surface-initiated atom transfer radical polymerization (ATRP) for improving cell immobilization and subsequent gene transfection. A simple aminolysis-based method was first used for the covalent immobilization of ATRP initiators on the PCL film. Well-defined P(DMAEMA) brushes were subsequently prepared via surface-initiated ATRP from the initiator-functionalized PCL surfaces. The P(DMAEMA) chains with a pK(a) of 7.0-7.3 were used for conjugating gelatin with a pI of 4.7 via electrostatic interaction. The amount of complexed gelatin increased as that of the grafted P(DMAEMA) layer. The cell-adhesion property on the functionalized PCL surface could be controlled by adjusting the ratio of P(DMAEMA)/gelatin. It was found that the gene transfection property on the immobilized cells was dependent on the density of the immobilized cells on the functionalized PCL film. With the good cell-adhesive nature of gelatin and the efficient gene transfection on the dense immobilized cells, the incorporating the suitable of P(DMAEMA)/gelatin complexes onto PCL surfaces could endow the PCL substrates new and interesting properties for potential tissue engineering applications.

Improvement of hemocompatibility of polycaprolactone film surfaces with zwitterionic polymer brushes.

Polycaprolactone (PCL) has been widely adopted as a scaffold biomaterial, but further improvement of the hemocompatibility of a PCL film surface is still needed for wide biomedical applications. In this work, the PCL film surface was functionalized with zwitterionic poly(3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate) (P(DMAPS)) brushes via surface-initiated atom transfer radical polymerization (ATRP) for enhancing hemocompatibility. Kinetics study revealed an approximately linear increase in graft yield of the functional P(DMAPS) brushes with polymerization time. The blood compatibilities of the modified PCL film surfaces were studied by platelet adhesion tests of platelet-rich plasma and human whole blood, hemolysis assay, and plasma recalcification time (PRT) assay. The improvement of hemocompatibility is dependent on the coverage of the grafted P(DMAPS) brushes on the PCL film. Lower or no platelet and blood cell adhesion was observed on the P(DMAPS)-grafted film surfaces. The P(DMAPS) grafting can further decrease hemolysis and enhance the PRT of the PCL surface. With the versatility of surface-initiated ATRP and the excellent hemocompatibility of zwitterionic polymer brushes, PCL films with desirable blood properties can be readily tailored to cater to various biomedical applications.

Comb-shaped conjugates comprising hydroxypropyl cellulose backbones and low-molecular-weight poly(N-isopropylacryamide) side chains for smart hydrogels: synthesis, characterization, and biomedical applications.

Hydroxypropyl cellulose (HPC) possesses a lower critical solution temperature (LCST) above 40 °C, while the poly(N-isopropylacrylamide) (P(NIPAAm)) exhibits a LCST of about 32 °C. Herein, comb-shaped copolymer conjugates of HPC backbones and low-molecular-weight P(NIPAAm) side chains (HPC-g-P(NIPAAm) or HPN) were prepared via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-functionalized HPC biopolymers. By changing the composition ratio of HPC and P(NIPAAm), the LCSTs of HPNs can be adjusted to be lower than the body temperature. The MTT assay from the HEK293 cell line indicated that HPNs possess reduced cytotoxicity. Some of the hydroxyl groups of HPNs were used as cross-linking sites for the preparation of stable HPN hydrogels. In comparison with the HPC hydrogels, the cross-linked HPN hydrogels possess interconnected pore structures and higher swelling ratios. The in vitro release kinetics of fluorescein isothiocyanate-labeled dextran and BSA (or dextran-FITC and BSA-FITC) as model drugs from the hydrogels showed that the HPN hydrogels are suitable for long-term sustained release of macromolecular drugs at body temperature.

Bifunctional conjugates comprising ß-cyclodextrin, polyethylenimine, and 5-fluoro-2'- deoxyuridine for drug delivery and gene transfer.

Earlier reports indicated that the conjugates (PEI(600)-CD, PC) of ß-cyclodextrin and low-molecular-weight polyethylenimine (PEI, M(w) 600) can be used as efficient gene carriers in glioma cancer therapy. Incorporating anticancer drugs onto PC conjugates may endow them with new and interesting properties for great applications. In this work, FU-PEI(600)-CD (FPC) conjugates comprising PC and 5-fluoro-2'-deoxyuridine (FdUrd) were prepared as new bifunctional anticancer prodrugs with improved therapeutic effects, as well as good gene transfer efficiency. In comparison with free FdUrd, FPC could inhibit proliferation and enhance cytotoxicity on glioma cells. The results of hematoxylin and eosin (HE) staining indicated that C6 cells treated with FPC shrunk more seriously. Unlike FdUrd, cell cycle analysis indicated that C6 cells were primarily arrested in the G1 phase in the presence of FPC. Cellular uptake of FPC in C6 cells was about 10 times higher than that of FdUrd. In addition, the in vitro and in vivo gene transfection indicated that FPC still exhibited good gene expression efficiency. With the ability to deliver drugs and transfer genes, such bifunctional FPC conjugates may have great potential applications in combination therapy of cancers.

UV-induced grafting processes with in situ formed photomask for micropatterning of two-component biomolecules.

We report a photolithographic process for micropatterning of two-component biomolecules on a transparent organic film via lateral functional polymer brushes of poly(sodium acrylate) (P(AA)) and poly(glycidyl methacrylate) (P(GMA)). The pattern of binary polymer brushes were prepared via consecutive UV-initiated grafting processes, under the assistance of the in situ formed poly (4,4'-bi[N-(4-vinylbenzyl) pyridinium]) (P(BVV)) photomask. The epoxy groups of the P(GMA) microdomains can be aminated for covalently coupling biotin, while the P(AA) microdomains were used for immobilizing immunoglobulin (IgG). The resulting biotin- and IgG-coupled microdomains interact specifically with their corresponding target proteins, avidin and anti-IgG, respectively.

Well-defined poly(2-hydroxyl-3-(2-hydroxyethylamino)propyl methacrylate) vectors with low toxicity and high gene transfection efficiency.

Successful gene delivery vectors for clinical translation should have high transfection efficiency and minimal toxicity. In this work, well-defined poly(2-hydroxyl-3-(2-hydroxyethylamino)propyl methacrylate) (PGEA) vectors with flanking cationic secondary amine and nonionic hydroxyl units were prepared via the ring-opening reaction of the pendant epoxide groups of poly(glycidyl methacrylate) with the amine moieties of ethanolamine. It was found that PGEA carriers possess very low toxicity (<10% of the toxicity of branched polyethylenimine (PEI, 25 kDa), while exhibiting surprisingly excellent transfection efficiency (higher than or comparable to that of PEI (25 kDa)) in different cell lines. A series of transfection and cytotoxicity assays revealed that PGEAs are highly promising as a new class of safe and efficient gene delivery vectors for future clinical gene therapies.

Rational design and latest advances of codelivery systems for cancer therapy.

Current treatments have limited effectiveness in treating tumors. The combination of multiple drugs or treatment strategies is widely studied to improve therapeutic effect and reduce adverse effects of cancer therapy. The codelivery system is the key to realize combined therapies. It is necessary to design and construct different codelivery systems in accordance with the variable structures and properties of cargoes and vectors. This review presented the typical design considerations about codelivery vectors for cancer therapy and described the current state of codelivery systems from two aspects: different types of vectors and collaborative treatment strategies. The commonly used loading methods of cargoes into the vectors, including physical and chemical processes, are discussed in detail. Finally, we outline the challenges and perspectives about the improvement of codelivery systems.

Comb-shaped copolymers composed of hydroxypropyl cellulose backbones and cationic poly((2-dimethyl amino)ethyl methacrylate) side chains for gene delivery.

Cationic polymers have been of interest and importance as nonviral gene delivery carriers. Herein, well-defined comb-shaped cationic copolymers (HPDs) composed of long biocompatible hydroxypropyl cellulose (or HPC) backbones and short poly((2-dimethyl amino)ethyl methacrylate) (or P(DMAEMA)) side chains were prepared as gene vectors via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-terminated HPC biopolymers. The P(DMAEMA) side chains of HPDs can be further partially quaternized to produce the quaternary ammonium HPDs (QHPDs). HPDs and QHPDs were assessed in vitro for nonviral gene delivery. HPDs exhibit much lower cytotoxicity and better gene transfection yield than high-molecular-weight P(DMAEMA) homopolymers. QHPDs exhibit a stronger ability to complex pDNA, due to increased surface cationic charges. Thus, the approach to well-defined comb-shaped cationic copolymers provides a versatile means for tailoring the functional structure of nonviral gene vectors to meet the requirements of strong DNA-condensing ability and high transfection capability.

Grafting of antibacterial polymers on stainless steel via surface-initiated atom transfer radical polymerization for inhibiting biocorrosion by Desulfovibrio desulfuricans.

To enhance the biocorrosion resistance of stainless steel (SS) and to impart its surface with bactericidal function for inhibiting bacterial adhesion and biofilm formation, well-defined functional polymer brushes were grafted via surface-initiated atom transfer radical polymerization (ATRP) from SS substrates. The trichlorosilane coupling agent, containing the alkyl halide ATRP initiator, was first immobilized on the hydroxylated SS (SS-OH) substrates for surface-initiated ATRP of (2-dimethylamino)ethyl methacrylate (DMAEMA). The tertiary amino groups of covalently immobilized DMAEMA polymer or P(DMAEMA), brushes on the SS substrates were quaternized with benzyl halide to produce the biocidal functionality. Alternatively, covalent coupling of viologen moieties to the tertiary amino groups of P(DMAEMA) brushes on the SS surface resulted in an increase in surface concentration of quaternary ammonium groups, accompanied by substantially enhanced antibacterial and anticorrosion capabilities against Desulfovibrio desulfuricans in anaerobic seawater, as revealed by antibacterial assay and electrochemical studies. With the inherent advantages of high corrosion resistance of SS, and the good antibacterial and anticorrosion capabilities of the viologen-quaternized P(DMAEMA) brushes, the functionalized SS is potentially useful in harsh seawater environments and for desalination plants.

Star-shaped cationic polymers by atom transfer radical polymerization from beta-cyclodextrin cores for nonviral gene delivery.

Cationic polymers with low cytotoxicity and high transfection efficiency have attracted considerable attention as nonviral carriers for gene delivery. Herein, well-defined and star-shaped CDPD consisting of beta-CD cores and P(DMAEMA) arms, and CDPDPE consisting of CDPD and P(PEGEEMA) end blocks (where CD = cyclodextrin, P(DMAEMA) = poly(2-(dimethylamino)ethyl methacrylate), P(PEGEEMA) = poly(poly(ethylene glycol)ethyl ether methacrylate)) for gene delivery were prepared via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-terminated beta-CD core. The CDPD and CDPDPE exhibit good ability to condense plasmid DNA (pDNA) into 100-200 nm size nanoparticles with positive zeta potentials of 25-40 mV at nitrogen/phosphate (N/P) ratios of 10 or higher. CDPD and CDPDPE exhibit much lower cytotoxicity and higher gene transfection efficiency than high molecular weight P(DMAEMA) homopolymers. A comparison of the transfection efficiencies between CDPD and P(DMAEMA) homopolymer indicates that the unique star-shaped architecture involving the CD core can enhance the gene transfection efficiency. In addition to reducing cytotoxicity, the introduction of a biocompatible P(PEGEEMA) end block to the P(DMAEMA) arms in CDPDPE can further enhance the gene transfection efficiency.

Active protein-functionalized poly(poly(ethylene glycol) monomethacrylate)-Si(100) hybrids from surface-initiated atom transfer radical polymerization for potential biological applications.

Protein-resistant poly(poly(ethylene glycol)monomethacrylate)-graft-Si(100), or Si-g-P(PEGMA) hybrids, were prepared via surface-initiated atom transfer radical polymerization (ATRP) of the poly(ethylene glycol)monomethacrylate (PEGMA) macromonomer from the hydrogen-terminated Si(100) surface (Si-H surface). The resultant robust Si-C bonded P(PEGMA) brushes can be further functionalized by the immobilization of human immunoglobulin (IgG) protein via different strategies, namely, the direct use of the alkyl halide chain ends preserved throughout the ATRP process and the postmodification of the hydroxyl side chains with by 1,1'-carbonyldiimidazole (CDI) or succinic anhydride (SA). The CDI exhibited a higher efficiency in activating the hydroxyl groups for coupling proteins. The surface density of the immobilized protein above 2.5 microg/cm(2) could be readily achieved. The distribution of active protein-docking sites on the Si-C bonded P(PEGMA) brushes can be also controlled by controlling the brush length. The resulting IgG-coupled Si-g-P(PEGMA) hybrid surface interacts only and specifically with the anti-IgG protein, while the dense P(PEGMA) brushes effectively prevent nonspecific protein binding and fouling. The simple concomitant incorporation of protein-resistant P(PEGMA) brushes and highly specific and active protein onto silicon surfaces via robust Si-C bonding should readily endow the silicon substrates with new and interesting properties for applications in silicon-based protein sensors or microarrays.