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1.
Acta Biomater ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32105832

RESUMO

Current tissue engineering strategies through scaffold-based approaches fail to recapitulate the complex three-dimensional microarchitecture and biochemical composition of the native Annulus Fibrosus tissue. Considering limited access to healthy annulus fibrosus cells from patients, this study explored the potential of bone marrow stromal cells (BMSC) to fabricate a scaffold-free multilamellar annulus fibrosus-like tissue by integrating micropatterning technologies into multi-layered BMSC engineering. BMSC sheet with cells and collagen fibres aligned at ~30° with respect to their longitudinal dimension were developed on a microgroove-patterned PDMS substrate. Two sheets were then stacked together in alternating directions to form an angle-ply bilayer tissue, which was rolled up, sliced to form a multi-lamellar angle-ply tissue and cultured in a customized medium. The development of the annulus fibrosus-like tissue was further characterized by histological, gene expression and microscopic and mechanical analysis. We demonstrated that the engineered annulus fibrosus-like tissue with aligned BMSC sheet showed parallel collagen fibrils, biochemical composition and microstructures that resemble the native disk. Furthermore, aligned cell sheet showed enhanced expression of annulus fibrosus associated extracellular matrix markers and higher mechanical strength than that of the non-aligned cell sheet. The present study provides a new strategy in annulus fibrosus tissue engineering methodology to develop a scaffold-free annulus fibrosus-like tissue that resembles the microarchitecture and biochemical attributes of a native tissue. This can potentially lead to a promising avenue for advancing BMSC-mediated annulus fibrosus regeneration towards future clinical applications.

2.
Electrophoresis ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32097991

RESUMO

Ion concentration polarization (ICP) imposes remarkable adverse effects on the energy conversion performance of the pressure-driven electrokinetic (EK) flows through a capillary system which can be equivalently treated as a battery. An optimized dimensionless numerical method is proposed in this study to investigate the causes and the effects of the ICP. Results show that remarkable ICP phenomena are induced under certain conditions such as high applied pressure, high surface charge density, and small inversed Debye length at dimensionless values of 6000, -10, and 0.5. Meanwhile, different factors influence the ICP and the corresponding electric properties in different ways. Particularly for the overall electric resistance, the applied pressure and the surface charge density mainly affect the variation amplitude and the level of the overall electric resistance when varying the output electric potential, respectively. Differently, the Debye length affects the overall electric resistance in both aspects. Ultimately, the induced ICP leads to significant non-linear current-potential curves. This article is protected by copyright. All rights reserved.

3.
J Mater Chem B ; 8(6): 1245-1255, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-31957760

RESUMO

Low loading capacity, poor accumulation rate and weak permeability at tumor sites have been identified as the critical barriers for anti-cancer nanomedicines (ANMs). We herein reported a reactive oxygen species (ROS)-activatable ANM of dextran-b-P(CPTMA-co-OEGMA) (DCPT). It aimed to meet the above challenges for improving the therapeutic efficiency of chemotherapy. In this system, camptothecin (CPT) was selected as a chemotherapy drug and poly(ethylene glycol)methyl ether methacrylate (OEGMA) played the role of a hydrophilic block to enhance the water solubility of polyprodrug micelles. At high ROS levels in the tumor microenvironment, the micelles could be disassembled, and simultaneously, the anti-cancer drug of CPT would be released from the DCPT micelles. The 4T1-tumor growth would be greatly inhibited by these two DCPT polyprodrugs, with outstanding in vivo biosafety. The results of both in vitro and in vivo studies indicated the superior therapeutic effects of DCPT. The rational design of polyprodrug nanomedicines may serve as a promising strategy for the development of tumor microenvironment-responsive ANMs, thus improving chemotherapy efficacy.

4.
Nanoscale ; 12(3): 1707-1718, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894823

RESUMO

Oxygen deficient TiO2-x nanoparticles (NPs) have been recognized as a category of new-fashioned photothermal agents to offer safer PTT. However, the surface of TiO2-x NPs is deficient in free active groups or radicals to conjugate functional therapeutic molecules, which seriously impedes their in-depth development for versatile medical applications. In this study, surface activation of TiO2-x NPs was realized by the facile conjugation of (3-aminopropyl)triethoxysilane (APTES) through the formation of a stable Si-O-Ti bond, and photosensitizer chlorin e6 (Ce6) was successfully modified onto the TiO2-x NP surface and with a considerably high loading content. The resultant TiO2-x@APTES/Ce6 (TAC) NPs displayed decent biosafety, rapid tumor enrichment and outstanding performance in photoacoustic (PA) imaging. Taking advantage of the intense photo-absorption in the near-infrared (NIR) region and high dose of conjugated Ce6, a powerful antitumor effect was realized based on the combination of hyperthermia-induced cell ablation and cytotoxic reactive oxygen species (ROS)-triggered apoptosis both in vitro and in vivo. Moreover, PA imaging guidance was exceptionally useful for locating the tumor position and optimizing the treatment regimens. Apart from Ce6, this elaborate modification strategy for TiO2-x is believed to be universal for steadily binding more versatile therapeutic agents, which would definitely favor the development of multifunctional TiO2-x-based nanocomplexes for enhanced tumor treatment.

5.
Biomaterials ; 234: 119771, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31951972

RESUMO

Glucose oxidase (GOx)-mediated starvation circumvents the energy supply for tumor growth, which has been proved as a potent tumor treatment modality. However, tumor hypoxia negatively affects the efficacy of oxygen-involved glucose decomposition reaction. Moreover, curative effect via glucose depletion is not usually satisfactory enough and adjuvant remedies are always required for a promoted tumor ablation. Herein, a multifunctional nanoreactor based on hollow Bi2Se3 nanoparticles was developed by loading oxygenated perfluorocarbon (PFC) and surface modification with GOx, which was exploited for an enhanced tumor starvation and highly sensitive photothermal therapy (PTT). GOx-mediated tumor starvation could impede the adenosine triphosphate (ATP) generation and further downregulate the expression of heat shock protein (HSP) to decrease the thermoresistance of cells. Afterwards, near infrared (NIR) laser irradiation was performed not only to trigger sensitized PTT but also to initiate the release of encapsulated oxygen to relieve local hypoxia. Then, such GOx-mediated tumor starvation would be further amplified, accompanying with secondary enhanced suppression of HSP. Both in vitro and in vivo investigations demonstrated that such nanoreactor can realize a fascinating therapeutic outcome with minimal adverse effects in virtue of the improved synergistic starvation therapy and PTT. Taken together, the proposed treatment paradigm may inspire the future development of more intelligent nanoplatforms toward high efficient cancer therapy.

6.
Biomater Sci ; 8(1): 353-369, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31724665

RESUMO

In spite of widespread applications of nano-photosensitizers, poor tumor penetration and severe hypoxia in the tumor microenvironment (TME) always result in an undesirable therapeutic outcome of photodynamic therapy (PDT). Herein, a biocompatible agarose-based hydrogel incorporated with sodium humate (SH), manganese oxide (MnO2) and chlorin e6 (Ce6) was synthesized as agarose@SH/MnO2/Ce6 through a "co-trapped" strategy during a sol-gel process and employed for combined photothermal therapy (PTT) and enhanced PDT. NIR-induced local hyperthermia is responsible for not only activating Ce6 release, but also triggering the catalytic decomposition of H2O2 mediated by MnO2 to relieve hypoxia. Such a hybrid hydrogel can realize deep tissue penetration through intratumoral injection, and exhibit remarkable tumor-site retention. Moreover, programmed laser irradiation led to an extremely high tumor growth inhibition rate of 93.8% in virtue of enhanced PTT/PDT. In addition, ultralow systemic toxicity caused by the hybrid hydrogel was further demonstrated in vivo. This reliable and eco-friendly hydrogel paves the way for the development of smart gel-based biomaterials, which respond to both exogenous and endogenous stimuli, towards the management of cancer and other major diseases.

7.
Biomater Sci ; 8(1): 473-484, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755481

RESUMO

Compared to normal tissues, unique conditions in the tumor microenvironment, such as a lower pH, can induce accurate release of a drug into specific lesions. This strategy provides an efficient approach to overcome the issues of unexpected drug leakage and poor circulation stability, thereby reducing the side effects and enhancing the effect of cancer treatment. In this study, we designed a class of acid activatable supramolecular nano-prodrugs (DOM@DOX) with a bottlebrush architecture based on the dextran (DEX) polysaccharide, which connects with a hydrophilic polyethylene glycol chain by atom transfer radical polymerization and further conjugates with an anticancer drug doxorubicin (DOX) at the backbone of the copolymer via an acidity-responsive hydrazine bond. Furthermore, the DOM@DOX prodrug has a high drug loading up to 48 wt% for DOX, and the prodrug can maintain a stable nano-sized spherical shape in aqueous solution by a self-assembly strategy. In an acidic environment inside tumor cells, the hydrazine bond of the prodrug breaks, leading to the release of DOX from parental micelles. Owing to the small size of the carrier, the prodrug exhibits good intratumoral permeability, good circulation stability and significant tumor suppression efficiency in tumor-bearing mouse models, which is beneficial for the development of new generation nanomedicine for enhanced chemotherapy.

8.
Sensors (Basel) ; 19(22)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766178

RESUMO

There are a huge number, and abundant types, of microalgae in the ocean; and most of them have various values in many fields, such as food, medicine, energy, feed, etc. Therefore, how to identify and separation of microalgae cells quickly and effectively is a prerequisite for the microalgae research and utilization. Herein, we propose a microfluidic system that comprised microalgae cell separation, treatment and viability characterization. Specifically, the microfluidic separation function is based on the principle of deterministic lateral displacement (DLD), which can separate various microalgae species rapidly by their different sizes. Moreover, a concentration gradient generator is designed in this system to automatically produce gradient concentrations of chemical reagents to optimize the chemical treatment of samples. Finally, a single photon counter was used to evaluate the viability of treated microalgae based on laser-induced fluorescence from the intracellular chlorophyll of microalgae. To the best of our knowledge, this is the first laboratory prototype system combining DLD separation, concentration gradient generator and chlorophyll fluorescence detection technology for fast analysis and treatment of microalgae using marine samples. This study may inspire other novel applications of micro-analytical devices for utilization of microalgae resources, marine ecological environment protection and ship ballast water management.

9.
J Mater Chem B ; 7(47): 7515-7524, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31714572

RESUMO

Microneedles are primarily designed for enhancing transdermal drug delivery in a minimally invasive manner. In particular, coated microneedles have attracted increasing attention due to the resulting mode of rapid and highly efficient drug administration. In this study, we developed a novel gelatin/sucrose film-coated poly(ethylene glycol)diacrylate (PEGDA) microneedle patch, which can effectively improve the skin permeability of therapeutic drugs and realize convenient and efficient drug administration. A simple and reliable technique was proposed to produce uniform film coatings on microneedles at room temperature. After introducing a prepolymer solution into the mold cavity, a film-coated microneedle patch was fabricated via a photo-induced polymerization process. Four categories of molecular models, including rhodamine B (RhB), bovine serum albumin (BSA), doxorubicin (DOX) and indocyanine green (ICG), were encapsulated into the gelatin/sucrose film to evaluate their transdermal delivery and therapeutic effects both in vitro and in vivo. The presented methodology represents a facile technique for rapid formation of film-coated microneedles for efficient transdermal delivery of small molecular drugs and large proteins.

10.
ACS Appl Mater Interfaces ; 11(44): 41127-41139, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31610123

RESUMO

Theranostic nanoplatforms that integrate therapy and diagnosis in a single composite have become increasingly attractive in the field of precise and efficient tumor treatment. Herein, a novel oxygen-deficient zirconia (ZrO2-x) nanosystem based on the conjugation of thiol-polyethylene glycol-amine (SH-PEG-NH2) and chlorin e6 (Ce6) was elaborately designed and established for efficacious photothermal/photodynamic therapy (PTT/PDT) and fluorescence/photoacoustic (FL/PA) bimodal imaging for the first time. The crystalline-disordered, PEGylated ZrO2-x nanoparticles (ZP NPs) displayed strong optical absorption in the near-infrared (NIR) window and were featured with significant photothermal conversion capacity. The ZP NPs were further covalently conjugated with Ce6 to form ZrO2-x@PEG/Ce6 (ZPC) NPs, which displayed a long circulatory half-life, efficient tumor accumulation, and outstanding FL/PA imaging performance. Moreover, the nanocomposites effectively generated cytotoxic intracellular reactive oxygen species (ROS) responsive to laser activation. Both cell studies and animal experiments explicitly demonstrated that ZPC NPs mediated remarkable tumor ablation with minimal systemic toxicity thanks to their tumor-specific PTT/PDT effect. Collectively, these findings may open up new avenues to broaden the application of oxygen-deficient ZrO2-x nanostructures as high-performance photothermal agents in tumor theranostics through rational design and accurate control of their physiochemical properties.

11.
ACS Appl Mater Interfaces ; 11(43): 40704-40715, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31577408

RESUMO

Anticancer nanomedicine-based multimodal imaging and synergistic therapy hold great promise in cancer diagnosis and therapy owing to their abilities to improve therapeutic efficiency and reduce unnecessary side effects, producing promising clinical prospects. Herein, we integrated chemotherapeutic drug camptothecin (CPT) and near-infrared-absorbing new indocyanine green (IR820) into a single system by charge interaction and obtained a tumor-microenvironment-activatable PCPTSS/IR820 nanoreactor to perform thermal/fluorescence/photoacoustic-imaging-guided chemotherapy and photothermal therapy simultaneously. Specifically, the generated PCPTSS/IR820 showed an excellent therapeutic agent loading content and size stability, and the trials in vitro and in vivo suggested that the smart PCPTSS/IR820 could deeply permeate into tumor tissues due to its suitable micellar size. Upon near-infrared laser irradiation, the nanoreactor further produced a terrific synergism of chemo-photo treatment for cancer therapy. Therefore, the PCPTSS/IR820 polyprodrug-based nanoreactor holds outstanding promise for multimodal imaging and combined dual therapy.

12.
Theranostics ; 9(21): 6314-6333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534553

RESUMO

Regenerated silk fibroin (SF) is a type of natural biomacromolecules with outstanding biocompatibility and biodegradability. However, stimulus-responsive SF-based nanocomplex has seldom been reported for application in tumor diagnosis and therapy. Methods: As a proof-of-concept study, a multifunctional SF@MnO2 nanoparticle-based platform was strategically synthesized using SF as a reductant and a template via a biomineralization-inspired crystallization process in an extremely facile way. Because of their mesoporous structure and abundant amino and carboxyl terminal residues, SF@MnO2 nanoparticles were co-loaded with a photodynamic agent indocyanine green (ICG) and a chemotherapeutic drug doxorubicin (DOX) to form a SF@MnO2/ICG/DOX (SMID) nanocomplex. Results: The obtained product was highly reactive with endogenous hydrogen peroxide (H2O2) in tumor microenvironment, which was decomposed into O2 to enhance tumor-specific photodynamic therapy (PDT). Moreover, SMID nanocomplex produced a strong and stable photothermal effect upon near-infrared (NIR) irradiation for photothermal therapy (PTT) owing to the distinct photothermal response of SF@MnO2 and stably conjugated ICG. The concurrent NIR fluorescence and magnetic resonance (MR) imaging in vivo both indicated effective tumor-specific enrichment of SMID nanoparticles via enhanced permeability and retention (EPR) effect. Animal studies further verified that SMID nanoparticles remarkably improved tumor inhibitive efficacy through combination PTT/PDT/chemotherapy with minimal systemic toxicity or adverse effect. Conclusion: This study demonstrated the promising potential of SF-based nanomaterial to address some of the key challenges in cancer therapy due to unfavorable tumor microenvironment for drug delivery.

13.
ACS Appl Mater Interfaces ; 11(39): 36130-36140, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31490659

RESUMO

Low delivery efficiency and limited tumor penetration of nanoparticle-based drug delivery systems (DDSs), the two most concerned issues in tumor therapy, have been considered as the "Achilles' heel" for tumor treatment. In this study, we have designed a highly sensitive dual-redox-responsive prodrug-based starlike polymer ß-CD-b-P(CPTGSH-co-CPTROS-co-OEGMA) (CPGR) for synergistic chemotherapy. The high glutathione (GSH) concentration and high reactive oxygen species (ROS) levels are in a dynamic equilibrium in the tumor microenvironment (TME) and could trigger the disintegration of CPGR micelles, which can promote the release of anticancer drug camptothecin (CPT) completely and intelligently. In order to verify the synergistic antitumor mechanism, two corresponding single-responsive ß-CD-b-P(CPTGSH-co-OEGMA) (CPG) and ß-CD-b-P(CPTROS-co-OEGMA) (CPR) were altogether prepared as contrast. Both in vitro and in vivo studies confirmed the enhanced anticancer activity of CPGR micelles in comparison of single responsive micelles. This work contributes to the orchestrated design of dual-redox-responsive DDSs for synergetic antitumor chemotherapy, which provides a good approach for the development of dual-redox-responsive nanomedicine.


Assuntos
Camptotecina , Micelas , Neoplasias Experimentais , Pró-Fármacos , Microambiente Tumoral/efeitos dos fármacos , Animais , Camptotecina/química , Camptotecina/farmacocinética , Camptotecina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Feminino , Células HeLa , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Oxirredução , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Colloids Surf B Biointerfaces ; 183: 110428, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415956

RESUMO

Tumor microenvironment (TME)-induced drug delivery technology is a promising strategy for improving low drug accumulation efficiency, short blood circulation and weak therapeutic effect. In this work, a dual-responsive (reduction- and pH-responsive) polyprodrug nanoreactor based on ß-cyclodextrin (ß-CD) was constructed for combinational chemotherapy. Specifically, the dual-responsive star polymeric prodrug was synthesized by atom transfer radical polymerization (ATRP) based on a starburst initiator of ß-CD-Br. The obtained polyprodrug contained a hydrophilic chain of poly-(ethylene glycol) methyl ether methacrylate (POEGMA) and a hydrophobic part of camptothecin (CPT) prodrug and poly[2-(diisopropylamino)ethyl methacrylate] (PDPA), denoted as ß-CD-PDPA-POEGMA-PCPT (CCDO for short). The obtained CCDO could form stable unimolecular micelles, which could be efficiently internalized by cancer cells. To enhance the curative effect, the anticancer agent doxorubicin (DOX) could be encapsulated into the hydrophobic cavity of the CCDO by hydrophobic-hydrophobic interaction. In vitro drug release studies showed that the obtained CCDO/DOX micelles controlled the release of active CPT and DOX occurring in a reductive environment and at low pH. In vitro cytotoxicity results suggested that the anticancer efficacy of dual-responsive CCDO/DOX micelles was superior to that of CCDO micelles. In addition, in vivo results verified good blood compatibility of the unimolecular micelles. This integrated dual-responsive drug delivery system may solve the low drug loading and poor controlled release problems found in traditional polymer-based drug carriers, providing an innovative and promising route for cancer therapy.

15.
Nanomedicine (Lond) ; 14(17): 2273-2292, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31414615

RESUMO

Aim: Hollow mesoporous copper sulfide nanocapsules conjugated with poly(ethylene glycol) (PEG), doxorubicin and chlorin e6 (HPDC) were synthesized for fluorescence imaging and multimodal tumor therapy. Materials & methods: HPDC were synthesized by encapsulating chlorin e6 and doxorubicin into PEGylated nanocapsules via a simple precipitation method. The photothermal/photodynamic effects, drug release, cellular uptake, imaging capacities and antitumor effects of the HPDCs were evaluated. Results: This smart nanoplatform is stimulus-responsive toward an acidic microenvironment and near infrared laser irradiation. Moreover, fluorescence imaging-guided and combined photothermal/photodynamic/chemotherapies of tumors were promoted under laser activation and led to efficient tumor ablation, as evidenced by exploring animal models in vivo. Conclusion: HPDCs are expected to serve as potent and reliable nanoagents for achieving superior therapeutic outcomes in cancer management.

16.
ACS Appl Mater Interfaces ; 11(32): 29330-29340, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31329411

RESUMO

Mitochondria-targeting cancer therapies have achieved unprecedented advances attributed to their superior ability for improving drug delivery efficiency and producing an enhanced therapeutic effect. Herein, we report a mitochondria-targeting camptothecin (CPT) polyprodrug system (MCPS) covalently decorated with a high-proportioned CPT content, which can realize drug release specifically responsive to a tumor microenvironment. The nonlinear structure of MCPS can form water-soluble unimolecular micelles with high micellar stability and improved drug accumulation in tumoral cells/tissues. Furthermore, a classical mitochondria-targeting agent, triphenylphosphonium bromide, was tethered in this prodrug system, which causes mitochondrial membrane potential depolarization and mediates the transport of CPT into mitochondria. The disulfide bond in MCPS can be cleaved by an intracellular reductant such as glutathione, leading to enhanced destruction of mitochondria DNA and cell apoptosis induced by a high level of reactive oxygen species. The systematic analyses both in vitro and in vivo indicated the excellent tumor inhibition effect and biosafety of MCPS, which is believed to be an advantageous nanoplatform for subcellular organelle-specific chemotherapy of cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Camptotecina , Neoplasias Mamárias Experimentais , Mitocôndrias , Pró-Fármacos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Camptotecina/química , Camptotecina/farmacocinética , Camptotecina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Feminino , Células HeLa , Humanos , Células MCF-7 , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Camundongos Endogâmicos BALB C , Micelas , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/metabolismo
17.
Biomed Microdevices ; 21(3): 58, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227909

RESUMO

Traditional immunomagnetic assays for the isolation and recovery of circulating tumor cells (CTCs) usually require sophisticated device or intense magnetic field to simultaneously achieve high capture efficiency and high throughout. In this study, a simple microfluidic chip featured with nanoroughened channel substrate was developed for effectively capture and release of CTCs based on an immunomagnetic chip-based approach. The nanoroughened substrate aims to increase the cell-surface contact area, facilitate the immobilization of magnet particles (MPs) and accommodate cell attachment tendency. Hep3B tumor cells were firstly conjugated with MPs that were functionalized with anti-EpCAM. Comparing with the flat channel, MPs modified tumor cells can be more effectively captured on nanoroughened substrate at the presence of the magnetic field. Upon the removal of magnetic field, these captured cells can be released from the device and collected for further analysis. Under the optimum operating conditions, the capture efficiency of tumor cells was obtained as high as ~90% with a detection limit of 10 cell per mL. Additionally, recovery rates of trapped tumor cells at various densities all exceeded 90% and their biological potencies were well retained by investigating the cell attachment and proliferation. Therefore, the present approach may potentially be used in clinical CTC analysis for cancer diagnosis and prognosis as well as the fundamental understanding of tumor metastasis.


Assuntos
Dimetilpolisiloxanos/química , Separação Imunomagnética/instrumentação , Nanoestruturas/química , Células Neoplásicas Circulantes/patologia , Adesão Celular , Linhagem Celular Tumoral , Proliferação de Células , Molécula de Adesão da Célula Epitelial/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Células Neoplásicas Circulantes/metabolismo , Propriedades de Superfície , Fatores de Tempo
18.
Langmuir ; 35(28): 9246-9254, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31251628

RESUMO

Design and construction of multifunctional theranostic nanoplatforms are still desired for cancer-effective treatment. Herein, a kind of polypyrrole (PPy)-based multifunctional nanocomposite was designed and successfully constructed for dual-model imaging and enhanced synergistic phototherapy against cancer cells. Through graphene oxide (GO) sheet coating, PPy nanoparticles (NPs) were effectively combined with polyethylene glycol chains, Au NPs, and IR820 molecules. The obtained PGPAI NPs showed promising ability for photoacoustic/computed tomography imaging. Under near-infrared light irradiation, the PPy core and IR820 molecule effectively generated heat and reactive oxygen species (ROS), respectively. Furthermore, the loaded Au NPs owning catalase-like activity produced oxygen by decomposing H2O2 (up-regulated in tumor region), enhancing the oxygen-dependent photodynamic therapy efficacy. The formed PGPAI NPs were also proved to own desirable photothermal conversion efficiency, photothermal stability, colloidal stability, cytocompatibility, and cellular internalization behaviors. Furthermore, cell assay demonstrated that PGPAI NPs displayed enhanced synergistic phototherapy efficacy against cancer cells. These developed multifunctional nanoplatforms are promising for effective cancer theranostic applications.

19.
Biomaterials ; 212: 39-54, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103945

RESUMO

The requirement for the favorable therapeutics against ulcerative colitis (UC) is that anti-inflammatory drugs can be specifically internalized by macrophages and subsequently be on-demand released to suppress inflammation. Herein, we developed a type of multi-bioresponsive anti-inflammatory drug (curcumin, CUR)-loaded nanoparticles (NPs) that were derived from natural silk fibroin and followed by surface functionalization with chondroitin sulfate (CS). The generated CS-CUR-NPs had a desired average particle size (175.4 nm), a uniform size distribution and negative surface charge (-35.5 mV). Strikingly, these NPs exhibited excellent bioresponsibility when triggered with the intrinsic stimuli (acidity, glutathione and reactive oxygen species) within activated macrophages, indicating that they could conceivably confer the on-demand intracellular drug release. Furthermore, we found that CS functionalization yielded notably targeted drug delivery to macrophages, and thereby enhanced the anti-inflammatory activities of NPs. Most importantly, animal experiments revealed that these nanotherapeutics could remarkably alleviate the symptoms of UC, maintain the homeostasis of intestinal microbiota and improve the survival rate of mice with UC through the route of oral administration or intravenous injection. Our results suggest that these facilely fabricated CS-CUR-NPs, which exhibit excellent biocompatibility, multi-bioresponsive drug release and macrophage-targeted capacity, could be exploited as a promising therapeutic platform for clinical UC treatment.

20.
Biomacromolecules ; 20(7): 2637-2648, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31141665

RESUMO

The physicochemical properties of nanomedicine can be altered with a tumor microenvironment, which influence the precise delivery of drug molecules to the lesion. Thus, the therapeutic efficiency is restrained. Here, a covalent self-assembled nanomicelle (CSNM) based starburst polyprodrug was constructed with the unimolecular micelle-templated self-assembly method and was expected to overcome biological barriers. It aimed to enhance the tumor penetration and chemotherapy efficiency of drugs. In CSNM, a hydrophilic copolymer was glued around a camptothecin (CPT) linked starburst polymeric prodrug [ß-CD-P (CPT- co-NH2)] for protecting the positive charge of the prodrug with a reduction-triggered reversibility in conjugation and activity. Then, the complex was tracelessly delivered into a negatively charged cell membrane, leading to enhanced cellular uptake. Finally, the disulfide bond in the CPT prodrug can be broken under the reductive microenvironment within tumor cells and liberated the CPT molecules. Both in vitro and in vivo results demonstrated the benefits of our CSNM system, including high drug loading, controllable drug release, excellent uptake by tumor cells and remarkable antitumor efficiency. In essence, our findings suggested CSNM as an innovative strategy for drug delivery in chemotherapy, producing a competitive versatility in the development of biomedicine.

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