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1.
Sci Rep ; 9(1): 13826, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554850

RESUMO

Enzymatic gold nanoparticles (B-GNPs) have been synthesized using a natural anticancer agent bromelain (a cysteine protease) and these nanoparticles were used to bioconjugate Cisplatin (highly effective against osteosarcoma and lung cancer). Cisplatin bioconjugated bromelain encapsulated gold nanoparticles (B-C-GNPs) were found profoundly potent against same cancers at much lower concentration with minimum side effects due to the synergistic effect of bromelain. The B-C-GNPs have been observed to inhibit the proliferation of osteosarcoma cell lines Saos-2 and MG-63 with IC50 estimation of 4.51 µg/ml and 3.21 µg/ml, respectively, and against small lung cancer cell line A-549 with IC50 2.5 µg/ml which is lower than IC50 of cisplatin against same cell lines. The B-GNPs/B-C-GNPs were characterized by TEM, UV-Visible spectroscopy, Zeta potential and DLS to confirm the production, purity, crystalline nature, stability of nanoemulsion, size and shape distribution. The change in 2D and 3D conformation of bromelain after encapsulation was studied by Circular Dichroism and Fluorometry, respectively. It was found that after encapsulation, a 19.4% loss in secondary structure was observed, but tertiary structure was not altered significantly and this loss improved the anticancer activity. The confirmation of bioconjugation of cisplatin with B-GNPs was done by UV-Visible spectroscopy, TEM, FTIR, 2D 1H NMR DOSY and ICP-MS. Further, it was found that almost ~4 cisplatin molecules bound with each B-GNPs nanoparticle.


Assuntos
Neoplasias Ósseas/metabolismo , Bromelaínas/farmacologia , Cisplatino/farmacologia , Ouro/química , Neoplasias Pulmonares/metabolismo , Osteossarcoma/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Células A549 , Neoplasias Ósseas/tratamento farmacológico , Bromelaínas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/química , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas Metálicas , Modelos Moleculares , Osteossarcoma/tratamento farmacológico , Conformação Proteica , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
2.
IET Nanobiotechnol ; 13(1): 23-29, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30964033

RESUMO

The stress conditions imposed by the impact of metal and non-metal oxide nanoparticles over plant systems enhances the synthesis of reactive oxygen species (ROS), resulting in oxidative damage at cellular level. The objective of this study was to synthesise the gold nanoparticles (GNps) from the leaves protein of Nicotiana tabacum L. cv. xanthi, its characterisation, and response on plant physiology and ROS scavenging activity on plants after exposure to different stresses. The authors have treated N. tabacum L. cv. xanthi plants with 100, 200, 300, 400, and 500 ppm biochemically synthesised GNps and examined physiological as well as biochemical changes. Results showed that biochemically synthesised GNps exposure significantly increased the seed germination (P < 0.001), root (P < 0.001), shoot growth (P < 0.001), and antioxidant ability (P < 0.05) of plants depending on bioengineered GNPs concentrations. Low concentrations (200-300 ppm) of GNps boosted growth by ∼50% and significantly increase in photosynthetic parameters such as total chlorophyll content (P < 0.05), membrane ion leakage (P < 0.05) as well as malondialdehyde (P < 0.05) content with respect to untreated plants under stress conditions. The high concentration (400-500 ppm) of GNps affected these parameters in a negative manner. The total antioxidant activity was also elevated in the exposed plants in a dose-dependent manner.


Assuntos
Sequestradores de Radicais Livres/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Nicotiana/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Química Verde , Folhas de Planta/química , Folhas de Planta/metabolismo , Plantas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Nicotiana/química
3.
Colloids Surf B Biointerfaces ; 160: 254-264, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28942160

RESUMO

Osteosarcoma or osteogenic sarcoma is the most common and prevalent cancerous tumor of bone and occurs especially in children and teens. Recent treatment strategy includes a combination of both chemotherapy and surgeries. Although, the use of single drug-based chemotherapy treatment remains unsatisfactory. Therefore, combinatorial therapy has emerged as a potential strategy for treatment with limited side- effects. Here, we evaluated the combinatorial anticancerous effect of cisplatin (CIS) and doxorubicin (DOX) bioconjugated bromelain encapsulated gold nanoparticles (B-AuNPs conjugated CIS and DOX) in the treatment of osteosarcoma. The synthesized B-AuNPs conjugated CIS and DOX were characterized by various characterization techniques like UV-vis spectroscopy, TEM, DLS and zeta potential to ensure the synthesis, size, shape, size distribution and stability. Drug loading efficiency bioconjugation of CIS and DOX was ensured by UV-vis spectroscopy. Bioconjugation of CIS and DOX was further confirmed using UV-vis spectroscopy, TEM, DLS, Zeta potential and FT-IR analysis. The combinatorial effect of CIS and DOX in B-AuNPs conjugated CIS and DOX showed highly improved potency against MG-63 and Saos-2 cells at a very low concentration where primary osteoblasts didn't show any cytotoxic effect. The apoptotic effect of B-AuNPs conjugated CIS and DOX on osteosarcoma and primary osteoblasts cells were analyzed by increased permeability of the cell membrane, condensed chromatin and deep blue fluorescent condensed nucleus. The results clearly showed that B-AuNPs conjugated CIS and DOX significantly improved the potency of both the chemotherapeutic drugs by delivering them specifically into the nucleus of cancer cells through caveolae-dependent endocytosis. Thus, the greater inhibitory effect of combinatorial drugs (B-AuNPs conjugated CIS and DOX) over single drug based chemotherapy would be of great advantage during osteosarcoma treatment.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Nanopartículas Metálicas/química , Nanoconjugados/química , Osteoblastos/efeitos dos fármacos , Antineoplásicos/química , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/química , Relação Dose-Resposta a Droga , Doxorrubicina/química , Combinação de Medicamentos , Composição de Medicamentos/métodos , Endocitose , Ouro/química , Humanos , Osteoblastos/metabolismo , Osteoblastos/patologia
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