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1.
J Pharm Anal ; 11(5): 529-540, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34178413

RESUMO

The deadly global outbreak of coronavirus disease-2019 (COVID-19) has forged an unrivaled threat to human civilization. Contemplating its profuse impact, initial risk management and therapies are needed, as well as rapid detection strategies alongside treatments with existing drugs or traditional treatments to provide better clinical support for critical patients. Conventional detection techniques have been considered but do not sufficiently meet the current challenges of effective COVID-19 diagnosis. Therefore, several modern techniques including point-of-care diagnosis with a biosensor, clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins that function as nuclease (Cas) technology, next-generation sequencing, serological, digital, and imaging approaches have delivered improved and noteworthy success compared to that using traditional strategies. Conventional drug treatment, plasma therapy, and vaccine development are also ongoing. However, alternative medicines including Ayurveda, herbal drugs, homeopathy, and Unani have also been enlisted as prominent treatment strategies for developing herd immunity and physical defenses against COVID-19. All considered, this review can help develop rapid and simplified diagnostic strategies, as well as advanced evidence-based modern therapeutic approaches that will aid in combating the global pandemic.

2.
Mol Biol Rep ; 47(5): 3745-3763, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32361897

RESUMO

Cancer cells need extensive energy supply for their uncontrolled cell division and metastasis which is exclusively dependent on neighboring cells, especially adipocytes. Herein, we have introduced a novel herbometallic nano-drug, Heerak Bhasma nanoparticle (HBNP) from natural resources showing high potential in the reduction of energy supply thereby promoting cell death in breast cancer cells. Inductively coupled plasma optical emission spectra (ICP-OES), atomic absorption spectra (AAS), Raman spectra, X-ray diffraction analyses confirmed the physicochemical properties of HBNP. The differential light scattering (DLS) and field emission scanning electron microscope (FESEM) analyzed the cell-permeable size of HBNP, whereas, cell viability assay confirmed the non-toxic effect. Seahorse energy efflux assay, apoptotic cell quantification, ROS, mitochondrial membrane potential, in vivo oxidative stress etc. were measured using standard protocol. The notable changes in cancer energy metabolism investigated by cellular Mito and Glyco-stress analyses confirmed the HBNP induced intracellular energy depletion. Also, a significant reduction in mitochondrial membrane potential and subsequently, extensive reactive oxygen species (ROS) generations were observed in presence of HBNP followed by the induction of cell apoptosis. The cell invasion and wound healing assay followed by reduced expression both protein (MMP 2, MMP 9) and cytokine (IL6, IL10) had signified the effectiveness of HBNP against cancer metastasis. In addition, HBNP also showed an excellent antitumor activity in vivo followed by developing healing characteristics due to oxidative stress. All these findings strongly suggest that HBNP has the potential to be the new cancer therapeutic. A schematic phenomenon represents the overall HBNP mediated anticancer activity via limitation of both fatty acid uptake and energy metabolism.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Medicina Ayurvédica/métodos , Nanopartículas Metálicas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
3.
Chem Sci ; 11(1): 141-147, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-32110365

RESUMO

Since temperature is one of the most significant physiological parameters that dictate the cellular status of living organisms, accurate intracellular temperature measurement is crucial and a valuable biomarker for the diagnosis and treatment of diseases. Herein, we introduce the foremost example of a non-conjugated polymer as a next generation fluorescent thermometer which is capable of addressing the key shortcomings including toxicity and thermal-induced fluorescence quenching associated with π-π conjugated system-based thermometers developed so far. We revealed, for the first time, the unique photophysical and aggregation-induced emission (AIE) characteristics of well-known thermoresponsive poly(N-vinylcaprolactam) (PNVCL) devoid of any classical fluorophore entity. PNVCL underwent a coil to globular conformational transition in an aqueous medium and appeared to be fluorescent above its lower critical solution temperature (LCST) near body temperature (38 °C). Eventually, this intriguing aspect enabled higher cellular uptake of PNVCL at the LCST boundary. By virtue of the AIE effect, the thermo-induced aggregation phenomenon has been ingeniously utilized to apply PNVCL as a novel fluorescent thermometer for intracellular temperature determination.

4.
Nanomedicine (Lond) ; 14(9): 1173-1189, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31050596

RESUMO

Aim: Preparation of a herbometallic nano-drug, Rasa Manikya nanoparticle (RMNP) and investigation of its antimicrobial, and anticancer activity. Materials & methods: Physicochemical characterizations of RMNP were performed using different analytical methods. The antimicrobial and anticancer potential of RMNPs were assessed by an in vitro cellular assay. Bacterial cell wall lysis was observed by field emission scanning electron microscopy and mitochondrial metabolism alteration factor was measured via standard method. Results: Physicochemical analysis confirmed that RMNP was rich in mineral constituents. Synergistic effect of RMNPs enhanced lysis of bacterial peptidoglycan layers and impaired cellular redox balance, GSH/NADPH level followed by induction of cell apoptosis. Conclusion: The present study confirms that RMNP can be used as a dual therapeutic option for combating drug-resistant microbial strains and breast cancer.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Arsenicais/química , Nanopartículas Metálicas/química , Estresse Oxidativo , Preparações de Plantas/química , Sulfetos/química , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Enterobacter/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Medicina Ayurvédica , Testes de Sensibilidade Microbiana , Oxirredução , Preparações de Plantas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Sulfetos/farmacologia
5.
Biomacromolecules ; 20(1): 546-557, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30521313

RESUMO

Delivery of clinically approved nonfluorescent drugs is facing challenges because it is difficult to monitor the intracellular drug delivery without incorporating any integrated fluorescence moiety into the drug carrier. The present investigation reports the synthesis of a pH-responsive autofluorescent polymeric nanoscaffold for the administration of nonfluorescent aromatic nitrogen mustard chlorambucil (CBL) drug into the cancer cells. Copolymerization of poly(ethylene glycol) (PEG) appended styrene and CBL conjugated N-substituted maleimide monomers enables the formation of well-defined luminescent alternating copolymer. These amphiphilic brush copolymers self-organized in aqueous medium into 25-68 nm nanoparticles, where the CBL drug is enclosed into the core of the self-assembled nanoparticles. In vitro studies revealed ∼70% drug was retained under physiological conditions at pH 7.4 and 37 °C. At endolysosomal pH 5.0, 90% of the CBL was released by the pH-induced cleavage of the aliphatic ester linkages connecting CBL to the maleimide unit. Although the nascent nanoparticle (without drug conjugation) is nontoxic, the drug conjugated nanoparticle showed higher toxicity and superior cell killing capability in cervical cancer (HeLa) cells rather than in normal cells. Interestingly, the copolymer without any conventional chromophore exhibited photoluminescence under UV light irradiation due to the presence of "through-space" π-π interaction between the C═O group of maleimide unit and the adjacent benzene ring of the styrenic monomer. This property helped us intracellular tracking of CBL conjugated autofluorescent nanocarriers through fluorescence microscope imaging. Finally, the 4-(4-nitrobenzyl)pyridine (NBP) colorimetric assay was executed to examine the ability of CBL-based polymeric nanomaterials toward alkylation of DNA.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Clorambucila/administração & dosagem , Nanoconjugados/química , Polímeros Responsivos a Estímulos/química , Antineoplásicos Alquilantes/química , Clorambucila/química , Liberação Controlada de Fármacos , Células HEK293 , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Luminescência , Células MCF-7 , Maleimidas/química , Polietilenoglicóis/química , Tensoativos/química
6.
Langmuir ; 30(44): 13430-7, 2014 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-25333268

RESUMO

Effects of counterions of side chain amino acid based polyelectrolytes (PEs) on the solubility in aqueous medium, pH responsiveness, thermal properties, and ionic conductivities have been appraised. Deprotection of the tert-butyl carbamate (Boc) group from poly(Boc-l-leucine methacryloyloxyethyl ester) [P(Boc-l-Leu-HEMA)] was carried out to produce PE with trifluoroacetate as an associative counteranion (1a). PEs with bis(trifluoromethylsulfonyl)imide and hexafluorophosphate counteranion were prepared through anion exchange reactions of 1a. Protonation of the neutralized polymer (2) obtained from 1a, followed by anion exchange, leads to the production of miscellaneous PEs bearing different counteranions, such as tetrafluoroborate, trifluoromethanesulfonate, chloride, and nitrate. Differential scanning calorimetry traces of the PEs reveal that the comparatively larger and weakly coordinated counteranions require less thermal energy to dissociate, and thus, the glass transition temperature (Tg) of the PEs fall off with an increase in the size of the counteranion. A remarkable conductivity of 2.1 mS/cm was obtained in deionized water when Cl(-) acted as the counteranion. Steric and electronic factors of the counteranion induce a change of transition pH in different PEs, although the chiroptical nature was retained, as confirmed by circular dichroism spectroscopy.

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