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1.
Nanoscale ; 15(38): 15686-15699, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37724853

RESUMO

Localized heat generation from manganese iron oxide nanoparticles (MIONPs) conjugated with chemotherapeutics under the exposure of an alternating magnetic field (magneto-chemotherapy) can revolutionize targeted breast cancer therapy. On the other hand, the lack of precise control of local temperature and adequate MIONP distribution in laboratory settings using the conventional two-dimensional (2D) cellular models has limited its further translation in tumor sites. Our current study explored advanced 3D in vitro tumor models as a promising alternative to replicate the complete range of tumor characteristics. Specifically, we have focused on investigating the effectiveness of MIONP-based magneto-chemotherapy (MCT) as an anticancer treatment in a 3D breast cancer model. To achieve this, chitosan-coated MIONPs (CS-MIONPs) are synthesized and functionalized with an anticancer drug (doxorubicin) and a tumor-targeting aptamer (AS1411). CS-MIONPs with a crystallite size of 16.88 nm and a specific absorption rate (SAR) of 181.48 W g-1 are reported. In vitro assessment of MCF-7 breast cancer cell lines in 2D and 3D cell cultures demonstrated anticancer activity. In the 2D and 3D cancer models, the MIONP-mediated MCT reduced cancer cell viability to about 71.48% and 92.2%, respectively. On the other hand, MIONP-mediated MCT under an AC magnetic field diminished spheroids' viability to 83.76 ± 2%, being the most promising therapeutic modality against breast cancer.

2.
ACS Omega ; 8(31): 27845-27861, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37576695

RESUMO

Brain cancer is one of those few cancers with very high mortality and low five-year survival rate. First and foremost reason for the woes is the difficulty in diagnosing and monitoring the progression of brain tumors both benign and malignant, noninvasively and in real time. This raises a need in this hour for a tool to diagnose the tumors in the earliest possible time frame. On the other hand, Raman spectroscopy which is well-known for its ability to precisely represent the molecular markers available in any sample given, including biological ones, with great sensitivity and specificity. This has led to a number of studies where Raman spectroscopy has been used in brain tumors in various ways. This review article highlights the fundamentals of Raman spectroscopy and its types including conventional Raman, SERS, SORS, SRS, CARS, etc. are used in brain tumors for diagnostics, monitoring, and even theragnostics, collating all the major works in the area. Also, the review explores how Raman spectroscopy can be even more effectively used in theragnostics and the clinical level which would make them a one-stop solution for all brain cancer needs in the future.

3.
Acta Biomater ; 136: 389-401, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34624554

RESUMO

Modelling of needle insertion in soft tissue has developed significant interest in recent years due to its application in robot-assisted minimally invasive surgeries such as biopsies and brachytherapy. However, this type of surgery requires real-time feedback and processing which complex computational models may not be able to provide. In contrast to the existing mechanics-based kinetic models, a simple multilayer tissue model using a Coupled Eulerian Lagrangian based Finite Element method has been developed using the dynamic principle. The model simulates the needle motion for flexible hollow bevel-angled needle (15° and 30°, 22 Gauge) insertion into porcine liver tissue, which includes material parameters obtained from unconfined compression testing of porcine liver tissue. To validate simulation results, needle insertion force and cutting force within porcine liver tissue were compared with corresponding experimental results obtained from a custom-built needle insertion system. For the 15° and 30° bevel-angle needles, the percentage error for cutting force (mean) of each needle compared to computational model, were 18.7% and 11.9% respectively. Varying the needle bevel angle from 30° to 15° results in an increase of the cutting force, but insertion force does not vary among the tested bevel angles. The validation of this computationally efficient multilayer Finite Element model can help engineers to better understand the biomechanical behaviour of medical needle inside soft biological tissue. Ultimately, this multilayer approach can help advance state-of-art clinical applications such as robot-assisted surgery that requires real-time feedback and processing. STATEMENT OF SIGNIFICANCE: The significance of the work is in confirming the effectiveness of multilayer material based finite element (FE) method to model biopsy needle insertion into soft biological porcine liver tissue. A multilayer Coupled Eulerian Lagrangian (CEL) based FE modelling technique allowed testing of heterogeneous, non-linear viscoelastic porcine liver tissue in a system, so direct comparison of needle tissue interaction forces on the intrinsic material (tissue) behaviour could be made. To the best of the authors' knowledge, the present research investigates for the first time modelling of a three dimensional (3D) hollow needle insertion using a multilayer stiffness model of biological tissue using FE based CEL method and presents a comparison of simulation results with experimental data.


Assuntos
Agulhas , Punções , Animais , Biópsia por Agulha , Simulação por Computador , Fígado , Modelos Biológicos , Suínos
4.
Adv Mater ; 33(40): e2008788, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34423493

RESUMO

Tendon disease constitutes an unmet clinical need and remains a critical challenge in the field of orthopaedic surgery. Innovative solutions are required to overcome the limitations of current tendon grafting approaches, and bioelectronic therapies show promise in treating musculoskeletal diseases, accelerating functional recovery through the activation of tissue regeneration-specific signaling pathways. Self-powered bioelectronic devices, particularly piezoelectric materials, represent a paradigm shift in biomedicine, negating the need for battery or external powering and complementing existing mechanotherapy to accelerate the repair processes. Here, the dynamic response of tendon cells to a piezoelectric collagen-analogue scaffold comprised of aligned nanoscale fibers made of the ferroelectric material poly(vinylidene fluoride-co-trifluoroethylene) is shown. It is demonstrated that motion-powered electromechanical stimulation of tendon tissue through piezo-bioelectric device results in ion channel modulation in vitro and regulates specific tissue regeneration signaling pathways. Finally, the potential of the piezo-bioelectronic device in modulating the progression of tendinopathy-associated processes in vivo, using a rat Achilles acute injury model is shown. This study indicates that electromechanical stimulation regulates mechanosensitive ion channel sensitivity and promotes tendon-specific over non-tenogenic tissue repair processes.


Assuntos
Eletrônica , Canais Iônicos/metabolismo , Tendões/fisiologia , Engenharia Tecidual/métodos , Animais , Colágeno/química , Módulo de Elasticidade , Estimulação Elétrica , Hidrocarbonetos Fluorados/química , Ratos , Regeneração/fisiologia , Transdução de Sinais , Tendões/citologia , Engenharia Tecidual/instrumentação , Alicerces Teciduais/química , Compostos de Vinila/química
5.
Nanomaterials (Basel) ; 11(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803430

RESUMO

Magnetic-plasmonic, Fe3O4-Au, core-shell nanoparticles are popular in many applications, most notably in therapeutics and diagnostics, and thus, the imaging of these nanostructures in biological samples is of high importance. These nanostructures are typically imaged in biological material by dark field scatter imaging, which requires an even distribution of nanostructures in the sample and, therefore, high nanoparticle doses, potentially leading to toxicology issues. Herein, we explore the nonlinear optical properties of magnetic nanoparticles coated with various thicknesses of gold using the open aperture z-scan technique to determine the nonlinear optical properties and moreover, predict the efficacy of the nanostructures in nonlinear imaging. We find that the magnetic nanoparticles coated with gold nanoseeds and thinner gold shells (ca. 4 nm) show the largest nonlinear absorption coefficient ß and imaginary part of the third-order susceptibility Im χ(3), suggesting that these nanostructures would be suitable contrast agents. Next, we combine laser dark field microscopy and epi-detected coherent anti-Stokes Raman (CARS) microscopy to image the uptake of magnetic-plasmonic nanoparticles in human pancreatic cancer cells. We show the epi-detected CARS technique is suitable for imaging of the magnetic-plasmonic nanoparticles without requiring a dense distribution of nanoparticles. This technique achieves superior nanoparticle contrasting over both epi-detected backscatter imaging and transmission dark field imaging, while also attaining label-free chemical contrasting of the cell. Lastly, we show the high biocompatibility of the Fe3O4 nanoparticles with ca. 4-nm thick Au shell at concentrations of 10-100 µg/mL.

6.
Nanomaterials (Basel) ; 10(12)2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33291591

RESUMO

Fe3O4-Au core-shell magnetic-plasmonic nanoparticles are expected to combine both magnetic and light responsivity into a single nanosystem, facilitating combined optical and magnetic-based nanotheranostic (therapeutic and diagnostic) applications, for example, photothermal therapy in conjunction with magnetic resonance imaging (MRI) imaging. To date, the effects of a plasmonic gold shell on an iron oxide nanoparticle core in magnetic-based applications remains largely unexplored. For this study, we quantified the efficacy of magnetic iron oxide cores with various gold shell thicknesses in a number of popular magnetic-based nanotheranostic applications; these included magnetic sorting and targeting (quantifying magnetic manipulability and magnetophoresis), MRI contrasting (quantifying benchtop nuclear magnetic resonance (NMR)-based T1 and T2 relaxivity), and magnetic hyperthermia therapy (quantifying alternating magnetic-field heating). We observed a general decrease in magnetic response and efficacy with an increase of the gold shell thickness, and herein we discuss possible reasons for this reduction. The magnetophoresis speed of iron oxide nanoparticles coated with the thickest gold shell tested here (ca. 42 nm) was only ca. 1% of the non-coated bare magnetic nanoparticle, demonstrating reduced magnetic manipulability. The T1 relaxivity, r1, of the thick gold-shelled magnetic particle was ca. 22% of the purely magnetic counterpart, whereas the T2 relaxivity, r2, was 42%, indicating a reduced MRI contrasting. Lastly, the magnetic hyperthermia heating efficiency (intrinsic loss power parameter) was reduced to ca. 14% for the thickest gold shell. For all applications, the efficiency decayed exponentially with increased gold shell thickness; therefore, if the primary application of the nanostructure is magnetic-based, this work suggests that it is preferable to use a thinner gold shell or higher levels of stimuli to compensate for losses associated with the addition of the gold shell. Moreover, as thinner gold shells have better magnetic properties, have previously demonstrated superior optical properties, and are more economical than thick gold shells, it can be said that "less is more".

7.
J Mech Behav Biomed Mater ; 111: 103896, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32791488

RESUMO

BACKGROUND: A thorough understanding of cutting-edge geometry and cutting forces of hollow biopsy needles are required to optimise needle tip design to improve fine needle aspiration procedures. OBJECTIVES: To incorporate the dynamics of needle motion in a model for flexible hollow bevel tipped needle insertion into a biological mimetic soft-gel using parameters obtained from experimental work. Additionally, the models will be verified against corresponding needle insertion experiments. METHODS: To verify simulation results, needle deflection and insertion forces were compared with corresponding experimental results acquired with an in-house developed needle insertion mechanical system. Additionally, contact stress distribution on needles from agar gel for various time scales were also studied. RESULTS: For the 15°, 30°, 45°, 60° bevel angle needles, and 90° blunt needle, the percentage error in needle deflection of each needle compared to experiments, were 7.3%, 9.9%, 8.6%, 7.8%, and 9.7% respectively. Varying the bevel angle at the needle tip demonstrates that the needle with a lower bevel angle produces the largest deflection, although the insertion force does not vary too much among the tested bevel angles. CONCLUSION: This experimentally verified computer-based simulation model could be used as an alternative tool for better understanding the needle-tissue interaction to optimise needle tip design towards improved biopsy efficiency.


Assuntos
Biomimética , Agulhas , Biópsia por Agulha , Simulação por Computador , Desenho de Equipamento , Movimento (Física)
8.
Ultrasound Med Biol ; 46(9): 2453-2463, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32546410

RESUMO

The ultrasonic visibility of a biopsy needle tip is of critical importance for the success and safety of endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) procedures. The aim of this study was to design a surface topology, in silico, which enhances the ultrasound visibility of a needle by controlling and optimising the direction of the reflections. Topographic enhancements to needle surface redirect scattered waves back to the transducer to enhance needle visibility, or "echogenicity." Echogenicity enhancement is demonstrated across insonification angles of 30°-90° on full-length scale of biopsy needles used in practice. By applying a textured surface across the full length of the needle surface, the signal being returned to the transducer can be tripled from that of a constant periodic dimple echogenic surface and seven times that of an untextured flat surface. Our first principles model provides a quantitative insight to echogenicity and its enhancement. The model allows in silico design of needles for USG-FNA and biopsy with enhanced echogenicity and consequent improvement in visibility, including but not limited to needle tip area.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Agulhas , Ultrassonografia , Desenho de Equipamento
9.
Drug Discov Today ; 25(7): 1245-1252, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32371139

RESUMO

To date, various chemically synthesized and biosynthesized nanoparticles, or hybrid nanosystems and/or nanoplatforms, have been developed under the umbrella of nanomedicine. These can be introduced into the body orally, nasally, intratumorally or intravenously. Successfully translating hybrid nanoplatforms from preclinical proof-of-concept to therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient stratification and target-driven design have improved patient outcomes. This review aims to identify gaps in our understanding of the current strengths of nanomedicine platforms in drug delivery and cancer theranostics. We report on the current approaches of nanomedicine at preclinical and clinical stages.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanomedicina/métodos , Medicina de Precisão/métodos , Nanomedicina Teranóstica/métodos
10.
ACS Nano ; 14(6): 7025-7037, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32441511

RESUMO

Diphenylalanine (FF) represents the simplest peptide building block that self-assembles into ordered nanostructures with interesting physical properties. Among self-assembled peptide structures, FF nanotubes display notable stiffness and piezoelectric parameters (Young's modulus = 19-27 GPa, strain coefficient d33 = 18 pC/N). Yet, inorganic alternatives remain the major materials of choice for many applications due to higher stiffness and piezoelectricity. Here, aiming to broaden the applications of the FF motif in materials chemistry, we designed three phenyl-rich dipeptides based on the ß,ß-diphenyl-Ala-OH (Dip) unit: Dip-Dip, cyclo-Dip-Dip, and tert-butyloxycarbonyl (Boc)-Dip-Dip. The doubled number of aromatic groups per unit, compared to FF, produced a dense aromatic zipper network with a dramatically improved Young's modulus of ∼70 GPa, which is comparable to aluminum. The piezoelectric strain coefficient d33 of ∼73 pC/N of such assembly exceeds that of poled polyvinylidene-fluoride (PVDF) polymers and compares well to that of lead zirconium titanate (PZT) thin films and ribbons. The rationally designed π-π assemblies show a voltage coefficient of 2-3 Vm/N, an order of magnitude higher than PVDF, improved thermal stability up to 360 °C (∼60 °C higher than FF), and useful photoluminescence with wide-range excitation-dependent emission in the visible region. Our data demonstrate that aromatic groups improve the rigidity and piezoelectricity of organic self-assembled materials for numerous applications.


Assuntos
Nanoestruturas , Fenilalanina , Dipeptídeos , Peptídeos
11.
ACS Appl Bio Mater ; 3(4): 2305-2313, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35025282

RESUMO

Elevating and monitoring the temperature of tumors using magnetic nanoparticles (MNPs) still presents a challenge in magnetic hyperthermia therapy. The efficient heating of tumor volume can be achieved by preparing MNPs with high magnetization values. The next-generation approach to magnetic resonance image (MRI)-guided magneto-chemotherapy of cancer based on high-magnetic-moment iron oxide nanoparticles is proposed. The proof of concept is validated by cellular MRI experiments on breast cancer cells. To explore magneto-chemotherapy, we developed high-magnetic-moment iron oxide (Fe3O4) nanoparticles (NPs) using base diisopropylamine (DIPA), which plays a dual role as reducing agent and surface stabilizer. Spherical NPs with ∼12 nm size and a high magnetization value of about 92 emu g-1 at room temperature are obtained by this unique method. A high specific absorption rate value of ∼717 wg-1 was obtained for Fe3O4 NPs in water at an alternating magnetic field of 20 kAm-1 and frequency of 267 kHz, which is attributed to the high magnetization value. The magneto-polymeric micelle structure is formed by using Pluronic F127, and anticancer drug doxorubicin is conjugated in the micelle by electrostatic interactions for magneto-chemotherapy. Finally, the magnetic resonance imaging (MRI)-guided magneto-chemotherapy was achieved on breast cancer (MCF7) cells with an overall ∼96% killing of cancer cells attained in 30 min of magneto-chmeotherapy.

13.
Colloids Surf B Biointerfaces ; 185: 110571, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683204

RESUMO

Cancer cells become resistant over the period to chemotherapeutic drugs and pose a challenging impediment for oncologists in providing effective treatment. Nanomedicine allows to overcome chemoresistance and is the focus of our investigation. Silica nanostructures have been highlighted as an interesting drug delivery platform in vitro and in vivo applications. Here we show the validity of nanomedicine approach for targeted chemotherapeutic cargo delivery to overcome chemoresistance in cancer cells both in vitro and in vivo. For demonstrating the concept, we functionalised ∼100 nm long porous silica nanoparticles (∼20 nm diameter ordered pore structure) by conjugating anticancer drug, cytochrome c enzyme and dual-function anticancer aptamer AS1411 in single supra-assembled nanocargos. The supra-assembly on the porous silica nanostructure allows for a high loading of catalytic enzyme cytochrome c, anticancer drug and aptamer. The silica supra-assembly is characterized by transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) surface area analysis. Conjugation of cargoes has been monitored at each step by UV-vis and Fluorescence spectroscopy. Finally, the constructed supra-assembled nanocarrier tested on chemoresistance colon cancer (HCT116) cells. A pH-responsive, intracellular theranostic cargo delivery has been achieved and the triple action of the nanocargo made an efficient killing of drug resistance colon cancer cells in vitro (∼ 92% cell death) through triplex therapy effects by supressing the P-glycoprotein (P-gp) level. Furthermore, in vivo animal toxicity studies demonstrated, the supra-assembled nanocargos have encouraging safety index to be used in cancer therapy and drug delivery applications.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Terapia de Alvo Molecular , Nanopartículas/química , Neoplasias/tratamento farmacológico , Dióxido de Silício/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/efeitos adversos , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Neoplasias/patologia , Distribuição Tecidual/efeitos dos fármacos
14.
ACS Biomater Sci Eng ; 5(6): 2669-2687, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33405601

RESUMO

Progress in nanomedicine has enabled the development of smart hybrid nanostructures (HNSs) for brain cancer theranostics, a novel platform that can diagnose the brain while concurrently beginning primary treatment, initiating secondary treatments where necessary, and monitoring the therapy response. These HNSs can release guest molecules/cargoes directly to brain tumors in response to external physical stimuli. Such physical stimulation is generally referred to as remote stimuli which can be externally applied examples include alternating magnetic field, visible or near-infrared light, ultrasound radiation, X-ray, and radiofrequency. The release of therapeutic cargoes in response to physical stimuli can be performed along with photodynamic therapy, photothermal therapy, phototriggered chemotherapeutics, sonodynamic therapy, electrothermal therapy, and magnetothermal therapy. Herein, we review different HNSs currently used as remotely triggered modalities in brain cancer, such as organic-inorganic HNSs, polymer micelles, and liposomes HNSs. We also summarize underlying mechanisms of remote triggering brain cancer therapeutics including single- and two-photon triggering, thermoresponsive HNSs, photoresponsive HNSs, magnetoresponsive HNSs, and electrically and ultrasound-stimulated HNSs. In addition to a brief synopsis of ongoing research progress on "smart" HNSs-based platforms of novel brain cancer therapeutics, the review offers an up-to-date development in this field for neuro-oncologists, material/nanoscientists, and radiologists so that a rapid clinical impact can be achieved through a convergence of multidisciplinary expertise.

15.
ACS Omega ; 3(6): 6143-6150, 2018 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30023942

RESUMO

Drug delivery monitoring and tracking in the human body are two of the biggest challenges in targeted therapy to be addressed by nanomedicine. The ability of imaging drugs and micro-/nanoengineered drug carriers and of visualizing their interactions at the cellular interface in a label-free manner is crucial in providing the ability of tracking their cellular pathways and will help understand their biological impact, allowing thus to improve the therapeutic efficacy. We present a fast, label-free technique to achieve high-resolution imaging at the mid-infrared (MIR) spectrum that provides chemical information. Using our custom-made benchtop infrared microscope using a high-repetition-rate pulsed laser (80 MHz, 40 ps), we were able to acquire images with subwavelength resolution (0.8 × λ) at very high speeds. As a proof-of-concept, we embarked on the investigation of nanoengineered polyelectrolyte capsules (NPCs) containing the anticancer drug, docetaxel. These NPCs were synthesized using a layer-by-layer approach built upon a calcium carbonate (CaCO3) core, which was then removed away with ethylenediaminetetraacetic acid. The obtained MIR images show that NPCs are attached to the cell membrane, which is a good step toward an efficient drug delivery. This has been confirmed by both three-dimensional confocal fluorescence and stimulated emission depletion microscopy. Coupled with additional instrumentation and data processing advancements, this setup is capable of video-rate imaging speeds and will be significantly complementing current super-resolution microscopy techniques while providing an unperturbed view into living cells.

16.
Biochem Biophys Rep ; 13: 63-72, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29349357

RESUMO

Recently lots of efforts have been taken to develop superparamagnetic iron oxide nanoparticles (SPIONs) for biomedical applications. So it is utmost necessary to have in depth knowledge of the toxicity occurred by this material. This article is designed in such way that it covers all the associated toxicity issues of SPIONs. It mainly emphasis on toxicity occurred at different levels including cellular alterations in the form of damage to nucleic acids due to oxidative stress and altered cellular response. In addition focus is been devoted for in vitro and in vivo toxicity of SPIONs, so that a better therapeutics can be designed. At the end the time dependent nature of toxicity and its ultimate faith inside the body is being discussed.

17.
Nat Mater ; 17(2): 180-186, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29200197

RESUMO

Piezoelectricity, the linear relationship between stress and induced electrical charge, has attracted recent interest due to its manifestation in biological molecules such as synthetic polypeptides or amino acid crystals, including gamma (γ) glycine. It has also been demonstrated in bone, collagen, elastin and the synthetic bone mineral hydroxyapatite. Piezoelectric coefficients exhibited by these biological materials are generally low, typically in the range of 0.1-10 pm V-1, limiting technological applications. Guided by quantum mechanical calculations we have measured a high shear piezoelectricity (178 pm V-1) in the amino acid crystal beta (ß) glycine, which is of similar magnitude to barium titanate or lead zirconate titanate. Our calculations show that the high piezoelectric coefficients originate from an efficient packing of the molecules along certain crystallographic planes and directions. The highest predicted piezoelectric voltage constant for ß-glycine crystals is 8 V mN-1, which is an order of magnitude larger than the voltage generated by any currently used ceramic or polymer.

18.
ACS Biomater Sci Eng ; 3(7): 1332-1340, 2017 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-33429691

RESUMO

A combination of chemotherapy with nonconventional nanoparticle based physical destruction therapy has been proposed clinically to reduce the prospect of evolution of drug resistance in cancer. Superparamagnetic nanoparticles have been actively used for synergetic cancer therapy including magnetic fluid hyperthermia (MFH) guided by magnetic resonance imaging (MRI). To explore this direction of potential applications in cancer therapy, we have functionalized superparamagnetic La0.7Sr0.3MnO3 nanoparticles (SPMNPs) with an oleic acid-polyethylene glycol (PEG) polymeric micelle (PM) structure, and loaded it with anticancer cancer drug doxorubicin (DOX) in a high loading capacity (∼60.45%) for in vitro delivery into cancer cells. The micellar structure provided good colloidal stability and biocompatibility. Upon drug loading, the cancer cell death rate of 89% was comparable to free DOX (75%) for 24 h, and that the counterstrategy of DOX conjugated SPMNPs-induced hyperthermia resulted the cancer cell extinction up to 80% under in vitro conditions within 30 min. In addition, the preliminary effect of protein corona formation on in vitro drug release and delivery was studied. Finally, in vivo bio distribution of micellar SPMNPs is observed in mice model for 50 mg kg-1 dose of SPMNPs. Taken together, polymeric micelle SPMNPs reported here can serve as a promising candidate for effective multimodal cancer theranostics such as in the combined chemotherapy-hyperthermia cancer therapy.

19.
J Mater Chem B ; 5(7): 1461-1470, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32264637

RESUMO

To achieve light-triggered drug release in cancer chemotherapy, we developed multimodal titanium dioxide (TiO2) nanocorals modified with methoxy polyethylene glycol (mPEG). TiO2 nanocoral-like structures were synthesized by optimizing a solvothermal method. The developed nanocoral structures were efficiently conjugated with chemotherapeutic drugs on the surfaces of the TiO2 nanoparticles. The mPEG on the surfaces of the multifunctional nanocorals effectively conjugated the drug and improved the biocompatibility of the nanocorals. Following UV light irradiation, the TiO2 nanocorals produce free radicals (˙OH and ˙O2 -) and are effective for drug release in cancer cells. Importantly, the amount of drug released from the multimodal TiO2 nanocorals can be regulated by UV-light irradiation time, which allows for further control of the anti-cancer effect. The multimodal TiO2 nanocorals exhibit a combination of light-activated, stimuli-triggered drug release for killing of cancer cell. The cytotoxicity, cellular uptake, and intracellular location of the formulations were evaluated in MCF7 cells. Our results showed that nanocoral-DOX complexes exhibited a greater cytotoxicity toward MCF7 cells than free DOX. Our work demonstrates that the therapeutic efficacy of DOX-loaded TiO2 nanocorals is strongly dependent on their loading mode and the chemotherapeutic effect is improved under UV light illumination, which provides a significant breakthrough for future applications of TiO2 as a light activated drug carrier in cancer chemotherapy.

20.
Phys Chem Chem Phys ; 18(31): 21331-9, 2016 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-27427175

RESUMO

Nanoparticle-based cancer diagnosis-therapy integrative systems (cancer theranostics) represent an emerging approach in oncology. To address this issue in the present work iron oxide (γ-Fe2O3-maghemite) nanoparticles (IONPs) were encapsulated within the matrix of (bis(p-sulfonatophenyl)phenylphosphine)-methoxypolyethylene glycol-thiol (mPEG) polymer vesicles using a two-step process for active chemotherapeutic cargo loading in cancer theranostics. This formation method gives simple access to highly reactive surface groups present on IONPs together with good control over the vesicle size (50-100 nm). The simultaneous loading of a chemotherapeutic drug cargo (doxorubicin) and its in vitro release in cancer cells was achieved. The feasibility of controlled drug release under different pH conditions was demonstrated in the case of encapsulated doxorubicin molecules, showing the viability of the concept of stimulated drug delivery for magneto-chemotherapy. These polymer-magnetic nanocargoes (PMNCs) exhibit enhanced contrast properties that open potential applications for magnetic resonance imaging. These self-assembled magnetic polymersomes can be used as efficient multifunctional nanocarriers for combined therapy and imaging.


Assuntos
Sistemas de Liberação de Medicamentos , Hipertermia Induzida , Nanopartículas de Magnetita , Neoplasias/diagnóstico , Neoplasias/terapia , Animais , Portadores de Fármacos , Compostos Férricos , Humanos , Imageamento por Ressonância Magnética
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