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1.
Biomed Mater ; 19(4)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38871001

RESUMO

Oral cancer accounts for 50%-70% of all cancer-related deaths in India and ranks sixth among the most frequent cancers globally. Roughly 90% of oral malignancies are histologically arise from squamous cells and are therefore called oral squamous cell carcinoma. Organic polycations known as biogenic polyamines, for example, putrescine (Put), spermidine (Spd), and spermine (Spm), are vital for cell proliferation, including gene expression control, regulation of endonuclease-mediated fragmentation of DNA, and DNA damage inhibition. Higher Spm and Spd levels have been identified as cancer biomarkers for detecting tumour development in various cancers. The current study utilises tannic acid, a polyphenolic compound, as a reducing and capping agent to fabricate AuNPs via a one-step microwave-assisted synthesis. The fabricated TA@AuNPs were utilised as a nanoprobe for colourimetric sensing of polyamines in PBS. When TA@AuNPs are added to the polyamine, the amine groups in polyamines interact with the phenolic groups of TA@AuNPs via hydrogen bonding or electrostatic interactions. These interactions cause the aggregation of TA@AuNPs, resulting in a red shift of the Surface Plasmon Resonance band of TA@AuNPs from 530 nm to 560 nm. The nanoprobe was found to be highly specific for Spm at low concentrations. TA@AuNPs were able to detect Spm successfully in artificial saliva samples. On recording the RGB values of the sensing process using a smartphone app, it was found that as the nanoparticles aggregated due to the presence of Spm, the intensity of theR-value decreased, indicating the aggregation of TA@AuNPs due to interaction with the polyamine.


Assuntos
Ouro , Nanopartículas Metálicas , Neoplasias Bucais , Poliaminas , Smartphone , Espermina , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Humanos , Nanopartículas Metálicas/química , Poliaminas/química , Ouro/química , Espermina/química , Putrescina/análise , Espermidina/química , Taninos/química , Ressonância de Plasmônio de Superfície , Colorimetria/métodos , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo
2.
ACS Appl Mater Interfaces ; 16(20): 25710-25726, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38739808

RESUMO

The present study investigated the concurrent delivery of antineoplastic drug, doxorubicin, and HER2 siRNA through a targeted theranostic metallic gold nanoparticle designed using polysaccharide, PSP001. The as-synthesized HsiRNA@PGD NPs were characterized in terms of structural, functional, physicochemical, and biological properties. HsiRNA@PGD NPs exposed adequate hydrodynamic size, considerable ζ potential, and excellent drug/siRNA loading and encapsulation efficiency. Meticulous exploration of the biocompatible dual-targeted nanoconjugate exhibited an appealing biocompatibility and pH-sensitive cargo release kinetics, indicating its safety for use in clinics. HsiRNA@PGD NPs deciphered competent cancer cell internalization, enhanced cytotoxicity mediated via the induction of apoptosis, and excellent downregulation of the overexpressing target HER2 gene. Further in vivo explorations in the SKBR3 xenograft breast tumor model revealed the appealing tumor reduction properties, selective accumulation in the tumor site followed by significant suppression of the HER2 gene which contributed to the exclusive abrogation of breast tumor mass by the HsiRNA@PGD NPs. Compared to free drugs or the monotherapy constructs, the dual delivery approach produced a synergistic suppression of breast tumors both in vitro and in vivo. Hence the drawings from these findings implicate that the as-synthesized HsiRNA@PGD NPs could offer a promising platform for chemo-RNAi combinational breast cancer therapy.


Assuntos
Neoplasias da Mama , Doxorrubicina , Inativação Gênica , RNA Interferente Pequeno , Receptor ErbB-2 , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Animais , Camundongos , Inativação Gênica/efeitos dos fármacos , Nanopartículas Metálicas/química , Ouro/química , Linhagem Celular Tumoral , Camundongos Nus , Camundongos Endogâmicos BALB C , Apoptose/efeitos dos fármacos
3.
J Biomater Sci Polym Ed ; 33(7): 858-877, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34963053

RESUMO

Irrespective of the labyrinth of fastidiously woven artificial scaffolds, the lack of biocompatibility hampers effective clinical translation, which is the definitive purpose of any biomedical system or device. Hence, the current exploration deals with the fabrication of scaffolds with enhanced bioactivities for wound healing. The methodology used for the fabrication of the scaffolds was electrospinning of the polysaccharide, which is isolated from tamarind seed kernel using the electrospinning process. To improve the antimicrobial activity of the scaffolds, in-house synthesized silver nanoparticles were added to the scaffolds. Wound healing and antimicrobial efficiency of the scaffolds were established in murine models. An insight into the wound healing mechanism was also analyzed using differentiation screening of stem cells grown on scaffolds. The results showed that newly synthesized scaffolds presented excellent wound healing ability along with antimicrobial activity. Furthermore, detailed toxicological evaluations through the histopathology and collagen staining wound sections, the probability of any off-target effects were also ruled out. Differentiation screening showed that adipogenesis was more prominent in cells attached to the scaffolds and markers of adipogenesis were strongly expressed in fluorescent microscopy. Thus we hope that the scaffolds mediate stem cell differentiation in wounds and promote a progressive healing response. Results thus obtained were encouraging and further studies need to embark on to establish the combined role in all aspects studied here.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Nanofibras , Animais , Diferenciação Celular , Camundongos , Polissacarídeos/farmacologia , Prata , Alicerces Teciduais , Cicatrização
4.
Int J Biol Macromol ; 103: 1000-1010, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28552725

RESUMO

Galactomannan (PSP001) isolated from the fruit rind of Punica granatum was demonstrated as an excellent antioxidant, immunomodulatory and anticancer agent both in vitro and in vivo models. Since the most lethal and debilitating attribute of cancer cells is their ability to evolve to a state of malignancy, with key features like increased angiogenesis, invasion, migration, colony formation, and metastasis, the present study focused on evaluating the effects of the galactomannan on tumor and malignancy. PSP001 effectively reduced the neovascularization in chick embryos highlighting its potential as an angiogenic inhibitor. Furthermore, the invasion, migration and clonogenic capacity of human and murine cancer cells were dramatically inhibited by PSP001. Evaluation of the molecular mechanism of its unique potential revealed the down regulation of key players including VEGF, MMP-2, and MMP-9 with marked elevation of TIMP-1 and TIMP-2. The anti-metastatic potential of PSP001 tested in pulmonary metastasis C57BL/6 mice model deciphered the combinatorial administration with vincristine deliberated better survival rates and decreased metastatic index. The angiogenic inhibition potential of PSP001 was further proved with peritoneal angiogenesis assay in BALB/c mice ascitic tumor model. The outcomes of the current investigation highlight the mode of action of antitumor galactomannan in the reduction of tumor malignancy.


Assuntos
Antineoplásicos/farmacologia , Lythraceae/química , Polissacarídeos/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Neovascularização Patológica/tratamento farmacológico , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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