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1.
Nanomedicine ; 57: 102738, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341011

RESUMO

Tumor recurrence, which happens as a result of persisting tumor cells and minor lesions after treatments like surgery and chemotherapy, is a major problem in oncology. Herein, a strategy to combat this issue by utilize a theranostic nanovaccine composed of photonic HCuS. This nanovaccine aims to eradicate cancer cells and their traces while also preventing tumor recurrence via optimizing the photothermal immune impact. Successful membrane targeting allows for the introduction of new therapeutic agents into the tumor cells. Together with co-encapsulated Toll-Like Receptors (TLR7/8) agonist R848 for activating T cells and maturing DCs, the combined effects of HCuS and ICG function as photothermal agents that generate heat in the presence of NIR light. Photothermal-mediated immunotherapy with therapeutic modalities proved successful in killing tumor cells. By activating the immune system, this new photonic nanovaccine greatly increases immunogenic cell death (ICD), kills tumor cells, and prevents their recurrence.


Assuntos
Nanopartículas , Fototerapia , Humanos , Nanovacinas , Nanomedicina Teranóstica , Microambiente Tumoral , Recidiva Local de Neoplasia , Linhagem Celular Tumoral , Imunoterapia , Nanopartículas/uso terapêutico
2.
Nanoscale ; 15(45): 18156-18172, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37947786

RESUMO

The wide applicability of acoustics in the life of mankind spread over health, energy, environment, and others. These acoustic technologies rely on the properties of the materials with which they are made of. However, traditional devices have failed to develop into low-cost, portable devices and need to overcome issues like sensitivity, tunability, and applicability in biological in vivo studies. Nanomaterials, especially 2D materials, have already been proven to produce high optical contrast in photoacoustic applications. One such wonder kid in the materials family is MXenes, which are transition metal carbides, that are nowadays flourishing in the materials world. Recently, it has been demonstrated that MXene nanosheets and quantum dots can be synthesized by acoustic excitations. In addition, MXene can be used as a mechanical sensing material for building piezoresistive sensors to realize sound detection as it produces a sensitive response to pressure and vibration. It has also been demonstrated that MXene nanosheets show high photothermal conversion capability, which can be utilized in cancer treatment and photoacoustic imaging (PAI). In this review, we have rendered the role of acoustics in the palette of MXene, including acoustic synthetic strategies of MXenes, applications such as acoustic sensors, PAI, thermoacoustic devices, sonodynamic therapy, artificial ear drum, and others. The review also discusses the challenges and future prospects of using MXene in acoustic platforms in detail. To the best of our knowledge, this is the first review combining acoustic science in MXene research.


Assuntos
Nanoestruturas , Pontos Quânticos , Acústica , Vibração
3.
J Mater Chem B ; 11(37): 9005-9018, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37712149

RESUMO

Photothermal therapy (PTT) is a noninvasive and effective thermal therapeutic approach. Near-infrared (NIR) light responsive organic nanoparticles (NPs) have been shown to enhance the efficacy of cancer PTT. However, photothermal ablation induced NPs are currently more effective in treating primary and metastatic cancer. Herein, we designed a NIR light responsive theranostic nanosystem that combines PTT with immunotherapy. The caffeic acid doped polyaniline NPs (CA-PANi) were explored for their potential as PTT agents and their ability to mediate immunogenic cell death (ICD). The nano-theranostic agent of CA-PANi functionalized with the RGD (Arg-Gly-Asp) peptide plays a functional role in targeting integrin receptor overexpressed cancer cells. Furthermore, to enhance the immune response in the immune suppressive tumor microenvironment (iTME), imiquimod (R837) a Toll-like receptor 7 agonist that can promote dendritic cell (DC) maturation greatly inhibits tumor growth and tumor recurrence by initiating a strong antitumor immune response. Therefore, combination of PTT and immunotherapy involving CA-PANi-R837-RGD (denoted as CPRR) to improve the therapeutic effect will provide a nanovaccine strategy for targeted antitumor therapy.


Assuntos
Neoplasias , Receptor 7 Toll-Like , Imiquimode/farmacologia , Imunoterapia , Adjuvantes Imunológicos , Diferenciação Celular , Neoplasias/tratamento farmacológico
4.
Nanotheranostics ; 7(1): 41-60, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593797

RESUMO

Theranostic nanoparticles (TNPs) is an efficient avenue that culminates both diagnosis and therapy into cancer treatment. Herein, we have formulated a theranostic nanocomposite (NC) with CuS being the ultra-small core component. To ensure stability to the NC, PEI was added which is a vital anchoring group polymer, especially on sulfide surfaces, and adds quality by being a better stabilizer and reducing agent. Additionally, to add stability, specificity, and added photothermal efficiency to the fabricated NC. In addition, encapsulation of indocyanine green (ICG), an efficient NIR absorber, and Folic acid (FA) were conjugated systematically, characterized, and analyzed for photo-stability. The photothermal conversion efficiency of the novel NC (CuS-PEI-ICG-FA) was analyzed at 808 nm, where the NC efficiently converted light energy to heat energy. The NC was also tested for hemocompatibility to clarify and also determined biocompatibility. Surprisingly, damage-associated molecular patterns (DAMPs) from post-PTT of tumor cells activate immunogenic cell death (ICD) for tumor-specific immune responses. The deserving photothermal performance and photo-stability makes the NC an ideal platform for photoacoustic imaging (PAI). A superior contrast was observed for PAI in a concentration-dependent manner enhancing the level of penetration into tissues, thereby better imaging. On account of this study, the newly formulated NC could be utilized as a "nanotheranostic" designed for therapeutic and image diagnostic agent of cancer biomedical applications.


Assuntos
Nanopartículas , Neoplasias , Humanos , Morte Celular Imunogênica , Fototerapia/métodos , Verde de Indocianina , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico
5.
J Mater Chem B ; 10(33): 6392-6403, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35971846

RESUMO

Nanomedicine with immunotherapy offers opportunities to target cancer in an effective manner; however, it remains challenging. We herein report a photothermal material loaded with immune-adjuvant combined immune checkpoint blockade for efficient cancer immunotherapy to target estrogen receptor-positive (ER+) breast cancer (BC). Endoxifen (END) expressly targets ER+ breast cancer cells. As a proof of concept of a targeting ER+ agent, END/NIR-responsive polyaniline (PANi)/a toll-like-receptor-7 agonist imiqumoid (R837) activating immune response co-encapsulated nanoparticles were formed as END-PANi-PVP@R837 NPs and found to be very appropriate as an NIR-responsive photothermal platform for versatile immunogenic cell death (ICD) in combination with an immune checkpoint PD-L1 blockade for development as an immunotherapy strategy. In this study, we concentrate on the therapeutic tactic of combining anti-PD-L1 with NPs, not only ablating cancer cells upon NIR irradiation but also providing strong anti-cancer immunity to destroy tumor progression after treatment. In both in vitro and in vivo experiments it was demonstrated that NPs could efficiently activate PTT to induce an immune response and immune resistance based on the PD-L1 checkpoint to ablate the tumor and inhibit tumor recurrence. We confirm the potency of the NPs, which exhibit high photothermal conversion efficacy and stability. The results demonstrate that the NP combination suppresses tumor cell growth at the tumor margin beyond effective PTT and immunotherapy.


Assuntos
Neoplasias da Mama , Fototerapia , Adjuvantes Imunológicos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Imiquimode , Inibidores de Checkpoint Imunológico , Imunoterapia/métodos , Medicina de Precisão , Receptor 7 Toll-Like
6.
ACS Appl Bio Mater ; 5(6): 2956-2964, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35620928

RESUMO

The advent of bio-nanotechnology has revolutionized nanodrug delivery by improving drug efficacy and safety. Nevertheless, acceptable carriers for therapeutic molecules are one of the most difficult challenges in drug delivery. Graphene material-based (GMB) and polymer-based drug-loaded nanocarriers have both demonstrated clinical advantages in delivering drugs of interest in vitro/in vivo. Cisplatin (CDDP) is an inorganic chemotherapeutic drug that is commonly used to treat a variety of cancers. However, its clinical use is associated with drug resistance and few side effects, which reduces its antitumor effects. Therefore, we developed a CDDP-loaded chitosan-functionalized graphene oxide nanocomposite (CDDP@CS-GO NC)-based nanodrug delivery system (NDDS). Flow cytometry and confocal imaging show that the CDDP@CS-GO NCs lead to significantly increased intracellular drug accumulation in tumor cells. Cancer cells take up the nanocomposite via endocytosis and can generate intracellular reactive oxygen species (ROS) to increase mitochondrial membrane potential loss (Δψm) and enable cytochrome-c release, followed by the dysregulation of Bcl-2 into the cytosol and activation of caspase-3 to induce cancer cell apoptosis. In vitro experiments demonstrated the excellent cancer therapeutic effect with few side effects of the carriers. CDDP@CS-GO NCs are expected to play an important role in responsive NDDSs for cancer therapy.


Assuntos
Grafite , Nanocompostos , Neoplasias do Colo do Útero , Cisplatino/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico
7.
Colloids Surf B Biointerfaces ; 216: 112584, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35617878

RESUMO

The present study was undertaken to investigate the ability of a drug curcumin-loaded polymer to inhibit the growth of cervical cancer cells by enhancing the anti-cancer efficiency of curcumin. We synthesized poly(methacryloyl beta-alanine) (PMBA) as a nanocarrier by radical polymerization in supercritical CO2. The results showed that the curcumin encapsulated and folic acid (FA)-treated PMBA (Poly@Cur-FA) for 24 h activated the reactive oxygen species-mediated programmed cell death machinery in HeLa cells. This remarkable effect of Poly@Cur-FA treatment was visualized using different fluorescent probes, which demonstrated that the Poly@Cur-FA treatment disrupted the cell membrane, as also supported by scanning electron microscopy observations. The effect of Poly@Cur-FA dispersion on the cells was observed under a transmission electron microscope. Further, the HeLa cells were treated with the polymer encapsulated curcumin and Bcl2 siRNA (Pol-Cur-siRNA) for 24 h, which effectively suppressed the Bcl2 and simulated the autophagic pathway. This co-delivery system was designed to inhibit curcumin efflux and can enhance the treatment efficacy by targeting multiple signaling pathways, including cell cycle, apoptotic, and autophagic pathways. Collectively, the Pol-Cur-siRNA system appears to offer an efficient combinational therapeutic strategy that might overcome the problems associated with the chemosensitivity against the standard synthetic anti-cancer drugs. To support the experimental data, an artificial neural network model was developed to foresee the drug and gene release behaviors.


Assuntos
Antineoplásicos , Curcumina , Nanopartículas , Neoplasias do Colo do Útero , Aminoácidos , Antineoplásicos/química , Dióxido de Carbono , Curcumina/química , Portadores de Fármacos/química , Feminino , Ácido Fólico/química , Células HeLa , Humanos , Nanopartículas/química , Polímeros/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética
8.
Biomacromolecules ; 22(6): 2472-2490, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34014660

RESUMO

Triple negative breast cancer (TNBC) is a breast cancer subtype. At present, TNBC patients do not have approved targeted therapy. Therefore, patients primarily depend on forceful systemic chemotherapy that has unavoidable harmful side effects, resulting in inadequate therapeutic outcomes and leading to a high mortality rate. Hence, there is an urgent need to develop targeted therapies for the TNBC populace. Developing a new nanotherapeutic approach of combinational therapy could be an effective alternative strategy. Therefore, we designed a combination of hyaluronan (HA)-polyaniline (PANi)-imiquimod (R837), denoted as HA-PANi/R837, nanoparticles (NPs) that exhibited a high extinction coefficient of 8.23 × 108 M-1 cm-1 and adequate photothermal conversion efficiency (PCE) (η = 41.6%), making them an efficient photothermal agent (PTA) that is highly beneficial for selective CD44-mediated photothermal ablation of TNBC tumors. Furthermore, co-encapsulation of R837 (toll-like receptor 7 agonist) immunoadjuvant molecules triggers an immune response against the tumor. The formed CD44-targeted HA-PANi/R837 NPs' selectivity incinerates the tumor under near-infrared (NIR)-triggered photothermal ablation, generating tumor-associated antigens and triggering R837 combination with anti-CTLA-4 for immunogenic cell death (ICD) activation to kill the remaining tumor cells in mice and protect against tumor relapse and metastasis. Our results demonstrated that novel HA-PANi/R837 NP-induced photothermal ICD achieved in CD44-targeted TNBC is a promising application.


Assuntos
Nanopartículas , Neoplasias de Mama Triplo Negativas , Animais , Linhagem Celular Tumoral , Humanos , Ácido Hialurônico , Morte Celular Imunogênica , Camundongos , Nanomedicina , Fototerapia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
9.
Nanoscale Adv ; 3(12): 3332-3352, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36133722

RESUMO

Nanotechnology is a branch of science dealing with the development of new types of nanomaterials by several methods. In the biomedical field, nanotechnology is widely used in the form of nanotherapeutics. Therefore, the current biomedical research pays much attention to nanotechnology for the development of efficient cancer treatment. Indocyanine green (ICG) is a near-infrared tricarbocyanine dye approved by the Food and Drug Administration (FDA) for human clinical use. ICG is a biologically safe photosensitizer and it can kill tumor cells by producing singlet oxygen species and photothermal heat upon NIR irradiation. ICG has some limitations such as easy aggregation, rapid aqueous degradation, and a short half-life. To address these limitations, ICG is further formulated with nanoparticles. Therefore, ICG is integrated with organic nanomaterials (polymers, micelles, liposomes, dendrimers and protein), inorganic nanomaterials (magnetic, gold, mesoporous, calcium, and LDH based), and hybrid nanomaterials. The combination of ICG with nanomaterials provides highly efficient therapeutic effects. Nowadays, ICG is used for various biomedical applications, especially in cancer therapeutics. In this review, we mainly focus on ICG-based combined cancer nanotherapeutics for advanced cancer treatment.

10.
ACS Appl Bio Mater ; 4(8): 6575-6588, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35006878

RESUMO

Integrated tumor-seeking nanomedicine (TSN) is designed to achieve a high therapeutic anticancer effect that is highly desirable for effective cancer treatment to overcome the detrimental effects of conventional therapies. However, direct administration of drugs cannot achieve a high level of specificity, which remains a formidable challenge. To address the confines, incorporation of multifunctionalities to maximize the specificity of TSN must be performed; TSN picks up multiple cargoes that are initially arrested at the core location and delivers each type simultaneously to a specified destination. Here, we introduce a valuable approach of Her2/neu-rich tumor cell surface-receptor-targeting TSN, which was highly pH-responsive and significantly realized the selective triple-therapeutic effects of blocking Her2/neu functions, chemotherapy, and phototherapy (photodynamic therapy (PDT)/photothermal therapy (PTT)). Therefore, the unprecedented selectivity of TSN provides a triple-therapeutic effect to spread the repertoire of "TSN" targets for future clinically relevant translation in improving breast cancer therapy.


Assuntos
Neoplasias da Mama , Fotoquimioterapia , Neoplasias da Mama/terapia , Feminino , Humanos , Nanomedicina , Fototerapia
11.
Bioorg Chem ; 97: 103709, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32146178

RESUMO

A series of novel 8-nitro quinoline-based thiosemicarbazone analogues were synthesized and characterized by various spectroscopic and single crystal X-ray analyses. The potent antitumor effects of synthesized compounds towards the cancer cells were evaluated by MTT assay. Amongst, the compound 3a exhibited the highest inhibitory activity and the compounds 3f and 3b were also showed significant activity. The molecular mechanistic studies of cell death have demonstrated that the treated potent compound 3a induced G1/S & G2/M phase cell cycle arrest and induced apoptosis via mitochondrial dysfunction and increased the production of cytotoxic ROS levels. The RT-PCR gene expression analysis revealed that the cell death induced by activation of caspase-3 dependent intrinsic apoptotic signaling pathway. Further, the molecular binding affinity of compounds with estrogen receptor alpha was calculated by molecular docking studies. Thus, novel 8-nitro quinoline-thiosemicarbazone analogues provide a unique tool for breast cancer therapeutic tactics.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cristalografia por Raios X , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Moleculares , Simulação de Acoplamento Molecular , Quinolinas/síntese química , Quinolinas/farmacocinética , Espécies Reativas de Oxigênio/metabolismo , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/farmacocinética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo
12.
Nanoscale Adv ; 2(8): 3209-3221, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-36134298

RESUMO

Porous iron oxide nanostructures have attracted increasing attention due to their potential biomedical applications as nanocarriers for cancer and many other therapies as well as minimal toxicity. Herbal anti-cancer agent thymoquinone loaded on Fe3O4 nanoparticles is envisaged to offer solution towards cancer treatment. The purpose of the present study was to investigate the efficacy of thymoquinone-loaded PVPylated Fe3O4 magnetic nanoparticles (TQ-PVP-Fe3O4 NPs) against triple-negative breast cancer (TNBC) cells. The porous PVPylated Fe3O4 NPs were prepared by a simple solvothermal process, whereas the thymoquinone drug was loaded via the nanoprecipitation method. Fourier transform infrared (FTIR) spectroscopic analysis confirmed the molecular drug loading, and surface morphological observation further confirmed this. The quantity of thymoquinone adsorbed onto the porous PVPylated Fe3O4 NPs was studied by thermogravimetric analysis (TGA). The positive surface charge of TQ-PVP-Fe3O4 NPs facilitates the interaction of the NPs with cancer (MDA-MB-231) cells to enhance the biological functions. In addition, the anticancer potential of NPs involving cytotoxicity, apoptosis induction, reactive oxygen species (ROS) generation, and changes in the mitochondrial membrane potential (ΔΨ m) of TNBC cells was evaluated. TQ-PVP-Fe3O4 NP-treated cells effectively increased the ROS levels leading to cellular apoptosis. The study shows that the synthesized TQ-PVP-Fe3O4 NPs display pH-dependent drug release in the cellular environment to induce apoptosis-related cell death in TNBC cells. Hence, the prepared TQ-PVP-Fe3O4 NPs may be a suitable drug formulation for anticancer therapy.

13.
ACS Appl Bio Mater ; 3(1): 186-196, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35019435

RESUMO

Although there has been considerable achievement in the field of breast cancer therapeutics, tackling the disturbing issue of highly potent triple-negative breast cancer (TNBC) still remains a hurdle in cancer therapeutics. Here, for the first time we propose a poly(ethylenimine) (PEI)-mediated approach for the synthesis of hyaluronic acid (HA) tagged cerium oxide nanoparticles (CePEI-NPs) as a therapeutic agent in TNBC. Primarily, the formulated HA-CePEI-NPs upon treatment displayed superior anticancer effect by exhibiting the loss of mitochondrial membrane potential (MMP). These particles acted as a nano reactor by the generation of reactive oxygen species (ROS) during the treatment. We further evaluated the caspase activity which divulgated the activation of caspases-3 and -9 while there was a decrease in the level of Bcl-2. The treatment also resulted in the release of cytochrome c (Cyt c), and in addition, features such as pynknosis and G2/M phase arrest were also noted. Hence the nano reactor property of nano ceria in activating mitochondrial-mediated intrinsic apoptosis highlights its promising role as a nano drug for therapeutic applications in TNBC.

14.
Medchemcomm ; 10(3): 439-449, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31015907

RESUMO

A series of unique dispiro analogues containing an oxindole pyrrolidine 8-nitroquinolone hybrid has been obtained through a one-pot three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the condensation of isatins and benzylamine with (E)-3-arylidene-2,3-dihydro-8-nitro-4-quinolones. The structures of the newly synthesized compounds were characterized by using different spectroscopic techniques and by X-ray diffraction studies of their regio- and stereochemistry. All the synthesized compounds were screened for in vitro cytotoxic activity against the human cervical cancer cell line HeLa. The compounds have exhibited potent inhibition against human cervical cancer cells and insignificant toxicity to normal cells. The compounds 6d, 6a, 6h, 6b, and 6e induced apoptosis of HeLa cells, through ROS influx. The expression levels of proteins involved in the mitochondrion-related pathways were detected, and Western blot analysis showed that apoptosis occurred via activation of caspase-3.

15.
Photodiagnosis Photodyn Ther ; 23: 244-253, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29964221

RESUMO

Herein, we posit a biocompatible and pH-switchable integrated nano-delivery of CBP/ICG to the in vitro and in vivo experiments demonstrate that nanoparticles (NPs) have insignificant toxicity and good biocompatibility, and possess excellent tumor targeting efficiency as evidenced by highly efficient tumor ablation under near -infrared (NIR) illumination. In addition, we have conjugated folic acid as a targeting ligand for folate receptor-targeted delivery. Particularly, targeted delivery of dual CBP/ICG loaded NPs provide targeted detection and transporting potential to specific receptor-expressing tumors, and then CBP interfering with DNA damage and ICG generates singlet oxygen as well as photothermal heat when irradiated with NIR for simultaneous trimodal PDT/PTT/Chemotherapy. Using an animal model, a dramatic reduction in tumor growth without any evidence of significant long-term toxicity to organs after administration of NPs for trimodal therapy subjecting to NIR illumination. Thus, the in vivo satisfactory antitumor trimodal combined efficacy concurrent with complete tumor eradication and promising potential for advanced clinical phototherapy.


Assuntos
Carboplatina/farmacologia , Ácido Fólico/farmacologia , Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Animais , Carboplatina/administração & dosagem , Carboplatina/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Quimioterapia Combinada , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacocinética , Concentração de Íons de Hidrogênio , Verde de Indocianina/administração & dosagem , Verde de Indocianina/farmacocinética , Verde de Indocianina/farmacologia , Raios Infravermelhos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química
16.
J Mater Chem B ; 6(21): 3555-3570, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32254451

RESUMO

In this article, we report the validation of cancer nanotherapy for the treatment of cancers using quercetin (Qtn). Much attention has been paid to the use of nanoparticles (NPs) to deliver drugs of interest in vitro/in vivo. Highly developed NPs-based nano drug delivery systems (NDDS) are an attractive approach to target cancer cell apoptosis, which is related to the onset and progression of cancer. Conventional chemotherapy has some notable drawbacks, such as lack of specificity, requirement of high drug doses, adverse effects, and gradual development of multidrug resistance (MDR), that decrease the efficacy of cancer therapy. To overcome these challenges of chemotherapy, the achievement of high drug loading in combination with low leakage at physiological pH, minimal toxicity toward healthy cells, and tunable controlled release at the site of action is an ongoing challenge. To assist drug delivery, we have prepared PVPylated-TiO2NPs containing Qtn with high loading efficiency (26.6% w/w) as a NDDS. The Qtn-PVPylated-TiO2NPs are uptaken via endocytosis by cancer cells and can generate intracellular reactive oxygen species (ROS) in order to increase mitochondrial membrane potential loss (Δψm) and enable release of cytochrome-c, followed by dysregulation of Bcl-2 into the cytosol and activation of caspase-3 to induce cancer cell apoptosis. These novel nanocombinations can be utilized to improve cancer nanotherapy by induction of apoptosis in vitro. Analysis at the molecular level revealed that the Qtn-PVPylated-TiO2NPs nanocombinations induced Δψm-mediated apoptotic signaling pathways. Overall, this study demonstrated that careful design of non-toxic nanocarriers for cancer nanotherapy can yield affordable NDDS.

17.
J Mater Chem B ; 6(27): 4539, 2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32254671

RESUMO

Correction for 'Mitochondrial dysfunction-induced apoptosis in breast carcinoma cells through a pH-dependent intracellular quercetin NDDS of PVPylated-TiO2NPs' by Thondhi Ponraj et al., J. Mater. Chem. B, 2018, 6, 3555-3570.

18.
ACS Biomater Sci Eng ; 4(5): 1880-1890, 2018 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33445343

RESUMO

Well-dispersed polyaniline (PANi) nanoparticles were successfully synthesized by simple oxidative polymerization of aniline in a two-phase system in the presence of poly(vinylpyrrolidone) (PVP) as a polymer shell agent, and citric acid was used as a doping acid instead of inorganic acids due to its better biocompatibility. TEM showed that the nanocomposites of PANi and PVP (PANi@PVP) assembled into core-shell like nanostructures uniformly. MTT results indicated that the PANi@PVP nanoparticles supported the survival of cells; IC50 could reach about 2.5 mg/mL, much higher than the IC50 value reported for PANi nanoparticles without PVP. Furthermore, in the presence of PVP, only exceeding PANi (>1.5 mg/mL) resulted in a comparable production of intracellular reactive oxygen species (ROS), the induction of apoptosis in PC-12 cells, and a weaker DNA fragmentation. TEM of PC-12 cell sections displayed that the cell morphological changes associated with the apoptosis were induced when exposed to a very high dose of PANi@PVP (3 mg/mL). The well-dispersed PANi@PVP combined with NIR irradiation achieved excellent photothermal conversion performance, which could kill cancer cell BEL-7402 in vitro effectively. Reflecting this well-dispersed property, the tumors in cancer bearing KM mice disappeared thoroughly after a single subcutaneous injection of PANi@PVP nanoparticles and subsequent NIR laser irradiation.

19.
Carbohydr Polym ; 160: 184-193, 2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-28115093

RESUMO

The current study is to develop a natural drug carrier with seaweed derived polymers namely κ-Carrageenan (κ-Car) for drug delivery applications. κ-Car is a natural polysaccharide which derived from edible red seaweeds, they are easily available, non-toxic, cost effective, biodegradable and biocompatible nature. Curcumin (Cur) is a yellow-orange polyphenol existing in turmeric, which is predominantly used as spice and food coloring agent. The ultimate use of polymeric composites, especially those composed of natural polymers, has become a very interesting approach in recent drug delivery applications, due to their non-toxicity and biological origin. In this study the primary approach which depends on the loading of Curcumin into κ-Carrageenan was accomplished, and which (κ-Car-Cur) an active drug carrier was developed for drug delivery against selected lung cancer cells (A549). Thus, the κ-Car-Cur was synthesized by solvent evaporation method followed by freeze drying, and it was further characterized. From this study, it has been reported that the high encapsulation efficiency, good stability, and successful release of Cur from the carrier (κ-Car) was achieved. The drug release was more active at acidic pH 5.0 with the cumulative release of 78%, which is the favorable condition present in tumor microenvironments. The in vitro cellular applications studies of κ-Car-Cur demonstrated that, κ-Car-Cur composites induced higher cytotoxicity against selected cancer cells than free Cur and effectively involved to trigger cellular apoptosis in A549 cancer cells. Further, it was also possessed that inhibition of cell growth and changes in metabolic activity of cancer cells are the unique characteristic features of cellular apoptosis, through reactive oxygen species (ROS) generation. It also observed that there was a decrease in mitochondrial membrane potential (ΔψmΔψm) which leads to a cellular apoptosis during treatment with κ-Car-Cur. Hence, the study outcomes may provide the potential outline for the use of κ-Car-Cur as a promising tool to deliver drugs at intracellular level.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Carragenina/química , Curcumina/farmacologia , Portadores de Fármacos/química , Células A549 , Humanos , Potencial da Membrana Mitocondrial , Espécies Reativas de Oxigênio/metabolismo
20.
Int J Biol Macromol ; 95: 1235-1245, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27840218

RESUMO

Lectins are proteins that show a variety of biological activities. Nevertheless, information on lectin from Gluttonous beauts and their anticancer activities are very limited. In this study, we purified a lectin from hemolymph of G. beauts and identified its molecular weight to be 66kDa. The effect of lectin at different concentrations (µg/mL) on the cell growth and apoptosis were evaluated against MCF-7 and MCF-10A cells, whereas cytotoxicity to the MCF-7 cells mediated by lectin was observed and the mechanism of action of the lectin in including apoptosis in cancer cells via the intrinsic pathway was also proposed. The MCF-7 cells were employed for in vitro studies on cytotoxicity, induction of apoptosis and apoptotic DNA fragmentation. In MCF-10A cells lectin did not show any adverse effect even at higher concentration. Cell cycle analysis also showed a significant cell cycle arrest on selected cells after lectin treatment. Western blotting suggested that lectin up regulates the apoptotic protein expression in MCF-7 cells while it down regulates the level of Bcl-2 expression.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Artrópodes/farmacologia , Artrópodes/química , Hemolinfa/química , Lectinas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Animais , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proteínas de Artrópodes/isolamento & purificação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Expressão Gênica , Humanos , Lectinas/isolamento & purificação , Células MCF-7 , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
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