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1.
J Phys Chem Lett ; : 10068-10078, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623821

RESUMO

Coherent polarization control of terahertz (THz) wave radiation in both the time-domain and the frequency-domain is significant in information technology, material science, and spectroscopic analysis. Elliptically polarized THz radiation is generally limited to chiral materials induced by circularly polarized light excitation. Herein, we demonstrate the coherent elliptically polarized THz radiation from few-layer tungsten diselenide (WSe2) in both the time-domain and the frequency-domain under linearly polarized femtosecond laser excitation. This coherent elliptical THz radiation is mainly dominated by in-plane anisotropic shift current and out-of-plane drift current, which is verified by the THz radiation dependence on the pump laser polarization angles, incident angles, and sample azimuthal angles systematically. The ellipticity and major axis direction of the elliptical THz wave can be efficiently controlled by either pump light polarization or sample azimuthal angle due to the controllable amplitudes and phases of two coherent orthogonal THz wave components. Our finding provides a method to distinguish drift and shift photocurrents in different directions and offers a unique design concept for elliptical THz generation with two-dimensional (2D) material physics.

2.
Polym Bull (Berl) ; : 1-16, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34566225

RESUMO

Nowadays, awareness about the burn wound is often considered difficult due to bacterial and other organism infections. The facile and eco-friendly preparations of antibiotic-loaded hydrogel-based bio-composites have great attention in the field of wound dressing for burn wound therapy and nursing care. In the present investigation, we have developed ciprofloxacin (CF)-encapsulated graphene-silk fibroin macromolecular hydrogel dressings material with unique chemical and physical properties to achieve the desirable antibacterial efficacy and healing activity. The antibacterial activity of prepared hydrogel was evaluated against bacterial pathogens treated with different concentrations of CF, which have been provided improved antibacterial activity on burn wound infection. In vitro, cytocompatibility evaluations were performed to imply the suitability of hydrogel on fibroblast cells, which has been dramatically related to in vivo wound healing. Furthermore, an in vivo wound healing analysis was carried out using a rat to observe the capability of the CF-incorporated GH/SF hydrogel matrix. Thus, this investigation widely demonstrates the healing ability of prepared hydrogel matrix and could be a significant landmark in the research on burn wound healing applications.

3.
Int Wound J ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414663

RESUMO

The development of biologically active multifunctional hydrogel wound dressings can assist effectively to wound regeneration and also has influenced multiple functions on wound injury. Herein, we designed a carbon-based composited injectable silk fibroin hydrogel as multifunctional wound dressing to provide effective anti-bacterial, cell compatibility and in vivo wound closure actions. Importantly, the fabricated injectable hydrogel exhibit sustained drug delivery properties, anti-oxidant and self-healing abilities, which confirm that composition of hydrogel is highly beneficial to tissue adhesions and burn wound regeneration ability. Frequently, designed injectable hydrogel can be injected into deep and irregular burn wound sites and would provide rapid self-healing and protection from infection environment with thoroughly filled wound area. Meanwhile, incorporated carbon nanofillers improve injectable hydrogel strength and also offer high fluid uptake to hydrogel when applied on the wound sites. In vitro MTT cytotoxicity assay on human fibroblast cell lines establish outstanding cytocompatibility of the injectable hydrogel and also have capability to support cell growth and proliferations. In vivo burn wound animal model results demonstrate that the hydrogel dressings predominantly influenced enhanced wound contraction and also promoted greater collagen deposition, granulation tissue thickness and vascularization. This investigation's outcome could open a new pathway to fabricate multifunctional biopolymeric hydrogel for quicker burn wound therapy and effectively prevents microenvironment bacterial infections.

4.
Small ; : e2102624, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34378338

RESUMO

Targeting B7-H3 chimeric antigen receptor (CAR) T cells has antitumor potential for therapy of non-small cell lung cancer (NSCLC) in preclinical studies. However, CAR T cell therapy remains a formidable challenge for the treatment of solid tumors due to the heterogeneous and immunosuppressive tumor microenvironment (TME). Nanozymes exhibit merits modulating the immunosuppression of the tumor milieu. Here, a synergetic strategy by combination of nanozymes and CAR T cells in solid tumors is described. This nanozyme with dual photothermal-nanocatalytic properties is endowed to remodel TME by destroying its compact structure. It is found that the B7-H3 CAR T cells infused in mice engrafted with the NSCLC cells have superior antitumor activity after nanozyme ablation of the tumor. Importantly, it is found that the changes altered immune-hostile cancer environment, resulting in enhanced activation and infiltration of B7-H3 CAR T cells. The first evidence that the process of combination nanozyme therapy effectively improves the therapeutic index of CAR T cells is presented. Thus, this study clearly supports that the TME-immunomodulated nanozyme is a promising tool to improve the therapeutic obstacles of CAR T cells against solid tumors.

5.
Int J Nanomedicine ; 16: 4559-4577, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267513

RESUMO

Purpose: Reactive oxygen species (ROS) are a group of signaling biomolecules that play important roles in the cell cycle. When intracellular ROS homeostasis is disrupted, it can induce cellular necrosis and apoptosis. It is desirable to effectively cascade-amplifying ROS generation and weaken antioxidant defense for disrupting ROS homeostasis in tumor microenvironment (TME), which has been recognized as a novel and ideal antitumor strategy. Multifunctional nanozymes are highly promising agents for ROS-mediated therapy. Methods: This study constructed a novel theranostic nanoagent based on PEG@Cu2-xS@Ce6 nanozymes (PCCNs) through a facile one-step hydrothermal method. We systematically investigated the photodynamic therapy (PDT)/photothermal therapy (PTT) properties, catalytic therapy (CTT) and glutathione (GSH) depletion activities of PCCNs, antitumor efficacy induced by PCCNs in vitro and in vivo. Results: PCCNs generate singlet oxygen (1O2) with laser (660 nm) irradiation and use catalytic reactions to produce hydroxyl radical (•OH). Moreover, PCCNs show the high photothermal performance under NIR II 1064-nm laser irradiation, which can enhance CTT/PDT efficiencies to increase ROS generation. The properties of O2 evolution and GSH consumption of PCCNs achieve hypoxia-relieved PDT and destroy cellular antioxidant defense system respectively. The excellent antitumor efficacy in 4T1 tumor-bearing mice of PCCNs is achieved through disrupting ROS homeostasis-involved therapy under the guidance of photothermal/photoacoustic imaging. Conclusion: Our study provides a proof of concept of "all-in-one" nanozymes to eliminate tumors via disrupting ROS homeostasis.


Assuntos
Homeostase/efeitos dos fármacos , Hipertermia Induzida/métodos , Raios Infravermelhos , Nanomedicina/métodos , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Animais , Catálise , Linhagem Celular Tumoral , Cério/química , Cobre/química , Glutationa/metabolismo , Humanos , Camundongos , Polietilenoglicóis/química , Sulfetos/química
6.
Am J Transl Res ; 13(3): 1799-1807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841704

RESUMO

OBJECTIVE: To investigate the effects of care bundles for patients with pressure ulcers and the impact on self-care efficacy. METHOD: A total of 160 patients with pressure ulcers were enrolled and divided into two groups using a lottery method. The control group (n=80) was cared for with routine nursing while the observation group (n=80) was additionally nursed with care bundles for 3 months. Both groups were compared in terms of grading of pressure ulcers, self-care efficacy, pressure ulcer management, awareness rate, and quality of life. RESULTS: At 3 months after nursing, the grading of pressure ulcers was significantly improved in both groups. The observation group exhibited higher incidence of pressure ulcers, unstageable and deep tissue injury than the control group (P<0.05). DSES scores were improved in both groups (P<0.05). Scores of daily living, health behavior, compliance behavior, and emotional management in the observation group were higher than those in the control group (P<0.05). The skills of pressure ulcer management were strengthened in both groups (P<0.05). Scores of nutritional support, repositioning, skin care, dressing changes, and pressure ulcer assessment in the observation group were higher than those in the control group (P<0.05). The observation group also exhibited higher scores in terms of diet, pressure ulcer monitoring, lesion staging, complications and knowledge of pressure ulcer triggers than the control group (P<0.05). Quality of life was significantly improved in both groups after 3 months of nursing. PH, RP, BP, GH, VT, SF, RE and MH scores in the observation group were higher than those in the control group (P<0.05). CONCLUSION: Care bundles can improve pressure ulcer grading, enhance patient self-care efficacy and skills of pressure ulcer management, and help improve patient awareness rates and quality of life for patients with pressure ulcers, which is worth of promoting.

7.
J Hematol Oncol ; 14(1): 21, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514401

RESUMO

BACKGROUND: B7-H3, an immune-checkpoint molecule and a transmembrane protein, is overexpressed in non-small cell lung cancer (NSCLC), making it an attractive therapeutic target. Here, we aimed to systematically evaluate the value of B7-H3 as a target in NSCLC via T cells expressing B7-H3-specific chimeric antigen receptors (CARs) and bispecific killer cell engager (BiKE)-redirected natural killer (NK) cells. METHODS: We generated B7-H3 CAR and B7-H3/CD16 BiKE derived from an anti-B7-H3 antibody omburtamab that has been shown to preferentially bind tumor tissues and has been safely used in humans in early-phase clinical trials. Antitumor efficacy and induced-immune response of CAR and BiKE were evaluated in vitro and in vivo. The effects of B7-H3 on aerobic glycolysis in NSCLC cells were further investigated. RESULTS: B7-H3 CAR-T cells effectively inhibited NSCLC tumorigenesis in vitro and in vivo. B7-H3 redirection promoted highly specific T-cell infiltration into tumors. Additionally, NK cell activity could be specially triggered by B7-H3/CD16 BiKE through direct CD16 signaling, resulting in significant increase in NK cell activation and target cell death. BiKE improved antitumor efficacy mediated by NK cells in vitro and in vivo, regardless of the cell surface target antigen density on tumor tissues. Furthermore, we found that anti-B7-H3 blockade might alter tumor glucose metabolism via the reactive oxygen species-mediated pathway. CONCLUSIONS: Together, our results suggest that B7-H3 may serve as a target for NSCLC therapy and support the further development of two therapeutic agents in the preclinical and clinical studies.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia Adotiva/métodos , Neoplasias Pulmonares/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Animais , Anticorpos Biespecíficos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Linhagem Celular Tumoral , Feminino , Humanos , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Ativação Linfocitária , Camundongos Endogâmicos NOD , Camundongos SCID , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Linfócitos T/transplante
8.
Phys Chem Chem Phys ; 22(37): 21428-21435, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32944724

RESUMO

Tunable optical properties play an important role in the high performance of optoelectronic applications based on two-dimensional (2D) transition metal carbide and nitride (MXene) materials. Herein, the optical properties of functionalized MXene monolayers Sc2CT2 (T = O and OH) are investigated by strain engineering. The strain-dependent linear optical properties of Sc2CT2 possess broadband optical response due to the geometry and orbital overlap effect. The peaks from the second-order nonlinear coefficient elements d (d15, d16, and d31) at around half the band-gap exhibit a redshift for Sc2CO2 (blueshift for Sc2C(OH)2) with the increase of strain. The strain-dependent d reveals that Sc2CO2 with -1268 pm V-1 %-1 has a larger photoelastic coefficient than that of Sc2C(OH)2 with -574 pm V-1 %-1 at 1% strain. Meanwhile, the photoelastic tensors can not only be increased but also reduced with the increase of strain due to the dispersion relation. Moreover, the azimuthal angle-dependent second harmonic generation (SHG) from strained Sc2CT2 monolayers depends highly on the strained states and the pumping photon energy. The results pave the way for the tunable, broadband, and anisotropic applications of nonlinear optoelectronic devices based on MXenes based on strain engineering.

9.
Front Pharmacol ; 11: 1089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848731

RESUMO

Chimeric antigen receptor (CAR)-modified natural killer (NK) cell therapy represents a kind of promising anti-cancer treatment because CAR renders NK cells activation and recognition specificity toward tumor cells. An immune checkpoint molecule, B7-H3, plays an inhibitory role in modulation of NK cells. To enhance NK cell functions, we generated NK-92MI cells carrying anti-B7-H3 CAR by lentiviral transduction. The expression of anti-B7-H3 CAR significantly enhanced the cytotoxicity of NK-92MI cells against B7-H3-positive tumor cells. In accordance with enhanced cytotoxicity, the secretions of perforin/granzyme B and expression of CD107a were highly elevated in anti-B7-H3 CAR-NK-92MI cells. Moreover, compared to unmodified NK-92MI cells, anti-B7-H3 CAR-NK-92MI cells effectively limited tumor growth in mouse xenografts of non-small cell lung cancer and significantly prolonged the survival days of mice. This study provides the rationale and feasibility of B7-H3-specific CAR-NK cells for application in adoptive cancer immunotherapy.

10.
Mol Pharm ; 17(10): 3720-3729, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32633977

RESUMO

The limited tumor tissue penetration of many nanoparticles remains a formidable challenge to their therapeutic efficacy. Although several photonanomedicines have been applied to improve tumor penetration, the first near-infrared window mediated by the low optical tissue penetration depth severely limits their anticancer effectiveness. To achieve deep optical tissue and drug delivery penetration, a near-infrared second window (NIR-II)-excited and pH-responsive ultrasmall drug delivery nanoplatform was fabricated based on BSA-stabilized CuS nanoparticles (BSA@CuS NPs). The BSA@CuS NPs effectively encapsulated doxorubicin (DOX) via strong electrostatic interactions to form multifunctional nanoparticles (BSA@CuS@DOX NPs). The BSA@CuS@DOX NPs had an ultrasmall size, which allowed them to achieve deeper tumor penetration. They also displayed stronger NIR II absorbance-mediated deep optical tissue penetration than that of the NIR I window. Moreover, the multifunctional nanoplatform preferentially accumulated in tumor sites, induced tumor hyperthermia, and generated remarkably high ROS levels in tumor sites upon NIR-II laser (1064 nm) irradiation. More importantly, our strategy achieved excellent synergistic effects of chemotherapy and phototherapy (chemophototherapy) under the guidance of photothermal imaging. The developed nanoparticles also showed good biocompatibility and bioclearance properties. Therefore, our work demonstrated a facile strategy for fabricating a multifunctional nanoplatform that is a promising candidate for deep tumor penetration as an effective antitumor therapy.

11.
Chem Commun (Camb) ; 55(95): 14255-14258, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31657388
12.
Nanoscale ; 11(35): 16614-16620, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31460543

RESUMO

Even though Si is the most cost efficient and extensively used semiconductor in modern optoelectronics, it is not considered to be an effective THz emitter due to its low carrier drift velocity and small saturated built-in electric field from the inversion layer. Herein, we present an effective way to enhance THz generation using a graphene/Si Schottky junction (GSSJ) excited with a femtosecond laser under electrical gating without rapid saturation and with high carrier drift velocity. This mixed-dimensional van der Waals interface demonstrates large saturation pump fluence with an invalid inversion layer by removing the native oxide on the Si surface. The THz emission amplitude from GSSJ effectively increases with the gate voltage. The THz emission from GSSJ under the same excitation conditions is stronger than that from the surface of InAs (100) and GaAs (100). The results not only show an efficient THz emission from GSSJ but also demonstrate the ability of THz generation for probing the mixed-dimensional van der Waals interface.

13.
Chem Commun (Camb) ; 55(44): 6209-6212, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31073580

RESUMO

In this study, pH-sensitive loaded retinal/indocyanine green (ICG) micelles were developed to realize novel approaches for cellular senescence-photothermal synergistic therapy to treat cancer. The micelles could enable effective multi-modal imaging in vivo guided therapy and show anticancer activity in vitro and in vivo with satisfactory biosafety.


Assuntos
Senescência Celular , Concentração de Íons de Hidrogênio , Verde de Indocianina/metabolismo , Micelas , Imagem Multimodal , Fototerapia/métodos , Retinaldeído/metabolismo , Nanomedicina Teranóstica , Humanos , Neoplasias/patologia
14.
J Phys Chem Lett ; 10(9): 2090-2100, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-30973733

RESUMO

Light-frequency conversion based on two-dimensional (2D) materials is of great importance for modern nano- and integrated photonics. Herein, we report both the intrinsic (from the pure WX2 (X = S, Se, and Te)) and extrinsic (from the interface of graphene/WX2) second-order nonlinear coefficient tensor from graphene/WX2 van der Waals (vdW) heterostructures by first-principles calculations. The prominent peaks in the dispersion relation of the intrinsic second-order nonlinear coefficient in monolayer WX2 are due to the Van Hove singularity in the high-symmetry point or along the high-symmetry line with high joint density of states. The enhanced nonlinear optical response in the infrared band can be achieved in graphene/WS2 vdW heterostructures, resulting from the interlayer charge transfer between graphene and WS2. The value of the intrinsic second-order nonlinear coefficients of graphene/WSe2 vdW heterostructures is 1.5 times larger than that of pure monolayer WSe2 at the band gap energy of monolayer WSe2 because of the enhanced carrier generation after the heterostructure formation. Different from pure monolayer WX2, azimuthal angle-dependent second harmonic generation from graphene/WX2 vdW heterostructures exhibits extraordinary rotational symmetry at different photon energies, which can be used to deduce the extrinsic second-order nonlinear coefficient. These results pave the way for the nonlinear optical coefficient design based on 2D heterostructures for nonlinear nanophotonics and integrated devices.

15.
Nanotechnology ; 30(19): 195705, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30699402

RESUMO

Broadband terahertz (THz) impedance matching is important for both spectral resolution improvement and THz anti-radar technology. Herein, graphene-silicon hybrid structure has been proposed for active broadband THz wave impedance matching with optical tunability. The main transmission pulse measured in the time domain indicates a modulation depth as high as 92.7% totally from the graphene-silicon interface. The interface reflection from the graphene-silicon junction implies that an impedance matching condition can be actively achieved by optical doping. To reveal the mechanism, we propose a graphene-silicon heterojunction model, which gives a full consideration of both the THz conductivity of graphene and the loss in doped junction layer. The theory fits well with the experimental results. This work proves active THz wave manipulation by junction effect and paves the way for active anti-reflection coating for THz components.

16.
J Phys Condens Matter ; 31(15): 153001, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30669133

RESUMO

Surfaces and interfaces are of particular importance for optoelectronic and photonic materials as they are involved in many physical and chemical processes such as carrier dynamics, charge transfer, chemical bonding, transformation reactions and so on. Terahertz (THz) emission spectroscopy provides a sensitive and nondestructive method for surface or interface analysis of advanced materials ranging from graphene to transition metal dichalcogenides, topological insulators, hybrid perovskites, and mixed-dimensional heterostructures based on 2D materials. In this review paper, we start with the THz radiation mechanisms under ultrafast laser excitation. Then we concentrate on the recent progresses of THz emission spectroscopy on the surface and interface properties of advanced materials, including transient surface photocurrents, surface nonlinear polarization, surface states, interface potential, and gas molecule adsorption/desorption processes. This novel spectroscopic method can not only promote the development of new and compact THz sources, but also provide a nondestructive optical method for surface and interface characterization of photocurrent and nonlinear polarization dynamics of materials.

17.
ACS Appl Mater Interfaces ; 10(41): 35599-35606, 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30252433

RESUMO

Graphene/semiconductor heterostructures demonstrate an improvement of traditional electronic and optoelectronic devices because of their outstanding charge transport properties inside and at the interfaces. However, very limited information has been accessed from the interfacial properties by traditional measurement. Herein, we present an active THz surface emission spectroscopy for the interface build-in potential and charge detrapping time constant evaluation from the interface of graphene on SiO2/Si (Gr/SiO2/Si). The active THz generation presents an intuitive insight into the depletion case, weak inversion case, and strong inversion case at the interface in the heterostructure. By analyzing the interface electric-field-induced optical rectification (EFIOR) in a strong inversion case, the intrinsic build-in potential is identified as -0.15 V at Gr/SiO2/Si interface. The interface depletion layer presents 44% positive THz intrinsic modulation by the reverse gate voltage and 70% negative THz intrinsic modulation by the forward gate voltage. Moreover, a time-dependent THz generation measurement has been used to deduce the charge detrapping decay time constant. The investigation will not only highlight the THz surface emission spectroscopy for the graphene-based interface analysis but also demonstrate the potential for the efficient THz intrinsic modulation as well as the enhancement of THz emission by the heterostructures.

18.
ACS Appl Mater Interfaces ; 10(1): 256-266, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29206023

RESUMO

The development of robust and nontoxic membrane-penetrating materials is highly demanded for nonviral gene delivery. Herein, a photosensitizer (PS)-embedded, star-shaped helical polypeptide was developed, which combines the advantages of multivalency-enhanced intracellular DNA uptake and light-strengthened endosomal escape to enable highly efficient gene delivery with low toxicity. 5,10,15,20-Tetrakis-(4-aminophenyl) porphyrin as a selected PS initiated ring-opening polymerization of N-carboxyanhydride and yielded a star-shaped helical polypeptide after side-chain functionalization with guanidine groups. The star polypeptide afforded a notably higher transfection efficiency and lower cytotoxicity than those of its linear analogue. Light irradiation caused almost complete (∼90%) endosomal release of the DNA cargo via the photochemical internalization (PCI) mechanism and further led to a 6-8-fold increment of the transfection efficiency in HeLa, B16F10, and RAW 264.7 cells, outperforming commercial reagent 25k PEI by up to 3 orders of magnitude. Because the PS and DNA cargoes were compartmentalized distantly in the core and polypeptide layers, respectively, the generated reactive oxygen species caused minimal damage to DNA molecules to preserve their transfection potency. Such multivalency- and PCI-potentiated gene delivery efficiency was also demonstrated in vivo in melanoma-bearing mice. This study thus provides a promising strategy to overcome the multiple membrane barriers against nonviral gene delivery.


Assuntos
Peptídeos/química , Animais , Técnicas de Transferência de Genes , Terapia Genética , Camundongos , Fármacos Fotossensibilizantes , Transfecção
19.
ACS Appl Mater Interfaces ; 9(28): 23476-23486, 2017 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-28653538

RESUMO

The rational design of gene vectors relies on the understanding of their structure-property relationship. Polypeptoids, which are structural isomers of natural polypeptides, hold great potential as gene delivery vectors due to their facile preparation, structural tunability, and most importantly, their desirable proteolytic stability. We herein designed a library of polypeptoids with different cationic side-chain terminal groups, degree of polymerizations (DPs), side-chain lengths, and incorporated aliphatic side chains, to unravel the structure-property relationships so that gene delivery efficiency can be maximized and cytotoxicity can be minimized. In HeLa cells, a polypeptoid bearing a primary amine side-chain terminal group exhibited remarkably higher transfection efficiency than that of its analogues containing secondary, tertiary, or quaternary amine groups. Elongation of the polypeptoid backbone length (from 28 to 251 mer) led to enhanced DNA condensation as well as cellular uptake levels, however it also caused higher cytotoxicity. Upon a proper balance between DNA uptake and cytotoxicity, the polypeptoid with a DP of 46 afforded the highest transfection efficiency. Elongating the aliphatic spacer between the backbone and side amine groups enhanced the hydrophobicity of the side chains, which resulted in notably increased membrane activities and transfection efficiency. Further incorporation of hydrophobic decyl side chains led to an improvement in transfection efficiency of ∼6 fold. The top-performing material identified, P11, mediated successful gene transfection under serum-containing conditions, outperforming the commercial transfection reagent poly(ethylenimine) by nearly 4 orders of magnitude. Reflecting its excellent serum-resistant properties, P11 further enabled effective transfection in vivo following intratumoral injection to melanoma-bearing mice. This study will help the rational design of polypeptoid-based gene delivery materials, and the best-performing material identified may provide a potential supplement to existing gene vectors.


Assuntos
Técnicas de Transferência de Genes , Animais , Cátions , Terapia Genética , Células HeLa , Humanos , Camundongos , Transfecção
20.
Biomater Sci ; 5(6): 1174-1182, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28513659

RESUMO

The transfection performance of polycations is often hampered by various systemic barriers that pose conflicting requirements for material design. Herein, we developed fluorinated, ROS-cleavable polyethylenimine (PEI) for effective and serum-resistant gene delivery to cancer cells, by harmonizing the inconsistency between DNA condensation and release, and the inconsistency between cellular internalization and serum stability. Low-molecular weight (MW) PEI was cross-linked with a diselenide-containing linker and further modified with fluorocarbon chains. The obtained high-MW DSe-PEI-F has potent DNA condensation as well as intracellular DNA delivery capabilities, while in the cytoplasm of cancer cells, it can rapidly degrade into low-MW segments upon ROS treatment to promote DNA release and reduce the material toxicity. As such, DSe-PEI-F showed high transfection efficiencies in cancer cells in the presence of serum, outperforming the commercial reagent PEI 25k by several orders of magnitude. This study thus provides an effective approach to overcome various barriers against non-viral gene delivery, which contributes to the development of a new class of gene vectors with high efficiency and low toxicity.


Assuntos
Reagentes para Ligações Cruzadas/metabolismo , DNA/administração & dosagem , Polietilenoimina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transfecção/métodos , Reagentes para Ligações Cruzadas/química , DNA/genética , Técnicas de Transferência de Genes , Halogenação , Células HeLa , Humanos , Compostos Organosselênicos/química , Compostos Organosselênicos/metabolismo , Polietilenoimina/química , Soro/metabolismo
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