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1.
Artigo em Inglês | MEDLINE | ID: mdl-37835126

RESUMO

Community engagement (CE) is essential to humanitarian assistance, and the social sciences have been credited in recent epidemics and disease outbreaks as having played a crucial, supportive role. Broadening this attention to other humanitarian fields, this scoping review asks what lessons learned can be found in grey and peer-reviewed literature on the integration of the social sciences in CE for conflicts and disasters. Using an analytical framework developed through a UNICEF-led project called Social Science for Community Engagement (SS4CE) in Humanitarian Action, we identified 1093 peer reviewed publications and 315 grey literature reports of possible relevance. The results show that only a small minority-18 publications and 4 reports-tangibly comment on the relevance of social sciences, mostly only in passing and implicitly. While social science techniques are used and the importance of understanding a community's cultural, linguistic, and religious context is emphasized, further discussion on the integration of transdisciplinary and multidisciplinary social sciences is absent. Furthermore, CE is mostly seen as an instrumental ('means to an end') involvement, for example to collect data in emergency situations and receive feedback on interventions, but not as a critical and transformative intervention. We conclude that unlike the attention given to social sciences in disease outbreaks, there is a knowledge gap and an accordingly proper planning and implementation gap regarding the potentiality of social science to improve CE across all humanitarian contexts of disasters and conflicts.


Assuntos
Desastres , Epidemias , Socorro em Desastres , Altruísmo , Surtos de Doenças
2.
Pharmaceutics ; 15(2)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36839970

RESUMO

In this study, the authors have designed biocompatible nano-vesicles using graphene oxide (GO) for the release of chlorambucil (CHL) drugs targeting cancerous cells. The GO sheets were first sulfonated and conjugated with folic acid (FA) molecules for controlled release and high loading efficiency of CHL. The chlorambucil (CHL) drug loading onto the functionalized GO surface was performed through π-π stacking and hydrophobic interactions with the aromatic planes of GO. The drug loading and "in vitro" release from the nano-vesicles at different pH were studied. The average particle size, absorption, and loading efficiency (%) of FA-conjugated GO sheets (CHL-GO) were observed to be 300 nm, 58%, and 77%, respectively. The drug release study at different pH (i.e., 7.4 and 5.5) showed a slight deceleration at pH 7.4 over pH 5.5. The amount of drug released was very small at pH 7.4 in the first hour which progressively increased to 24% after 8 h. The rate of drug release was faster at pH 5.5; initially, 16% to 27% in the first 3 h, and finally it reached 73% after 9 h. These observations indicate that the drug is released more rapidly at acidic pH with a larger amount of drug-loading ability. The rate of drug release from the CHL-loaded GO was 25% and 75% after 24 h. The biotoxicity study in terms of % cell viability of CHL-free and CHL-loaded GO against human cervical adenocarcinoma cell line was found to have lower cytotoxicity of CHL-loaded nano-vesicles (IC50 = 18 µM) as compared to CHL-free (IC50 = 8 µM). It is concluded that a high drug-loading efficiency and controlled release with excellent biotoxicity of CHL-GO offers an excellent application in the biomedical field.

3.
Pharmaceutics ; 15(1)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36678877

RESUMO

Triple-negative breast cancer (TNBC) is a life-threatening form of breast cancer which has been found to account for 15% of all the subtypes of breast cancer. Currently available treatments are significantly less effective in TNBC management because of several factors such as poor bioavailability, low specificity, multidrug resistance, poor cellular uptake, and unwanted side effects being the major ones. As a rapidly growing field, nano-therapeutics offers promising alternatives for breast cancer treatment. This platform provides a suitable pathway for crossing biological barriers and allowing sustained systemic circulation time and an improved pharmacokinetic profile of the drug. Apart from this, it also provides an optimized target-specific drug delivery system and improves drug accumulation in tumor cells. This review provides insights into the molecular mechanisms associated with the pathogenesis of TNBC, along with summarizing the conventional therapy and recent advances of different nano-carriers for the management of TNBC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36159728

RESUMO

Photodynamic therapy (PDT), as the name suggests is a light-based, non-invasive therapeutic treatment method that has garnered immense interest in the recent past for its efficacy in treating several pathological conditions. PDT has prominent use in the treatment of several dermatological conditions, which consequently have cosmetic benefits associated with it as PDT improves the overall appearance of the affected area. PDT is commonly used for repairing sun-damaged skin, providing skin rejuvenation, curbing pre-cancerous cells, treating conditions like acne, keratosis, skin-microbial infections, and cutaneous warts, etc. PDT mediates its action by generating oxygen species that are involved in bringing about immunomodulation, suppression of microbial load, wound-healing, lightening of scarring, etc. Although there are several challenges associated with PDT, the prominent ones being pain, erythema, insufficient delivery of the photosensitizing agent, and poor clinical outcomes, still PDT stands to be a promising approach with continuous efforts towards maximizing clinical efficacy while being cautious of the side effects and working towards lessening them. This article discusses the major skin-related conditions which can be treated or managed by employing PDT as a better or comparable alternative to conventional treatment approaches such that it also brings about aesthetic improvements thereof.

5.
Nanomedicine ; 44: 102572, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35671983

RESUMO

We previously reported that hydroxylated oxime ether lipids (OELs) efficiently deliver functional Dicer substrate siRNAs (DsiRNAs) in cells. Here, we explored in vivo utility of these OELs, using OEL4 as a prototype and report that surface modification of the OEL4 formulations was essential for their in vivo applications. These surface-modified OEL4 formulations were developed by inclusion of various PEGylated lipids. The vesicle stability and gene knock-down were dependent on the PEG chain length. OEL4 containing DSPE-PEG350 and DSPE-PEG1000 (surprisingly not DSPE2000) promoted gene silencing in cells. In vivo studies demonstrated that OEL4 vesicles formulated using 3 mol% DSPE-PEG350 accumulate in human lung cancer (A549-luc2) xenografts in mice and exhibit a significant increase in tumor to liver ratios. These vesicles also showed a statistically significant reduction of luciferase signal in tumors compared to untreated mice. Taken together, the scalable OEL4:DSPE-PEG350 formulation serves as a novel candidate for delivery of RNAi therapeutics.


Assuntos
Éter , Neoplasias Pulmonares , Animais , Éteres , Xenoenxertos , Humanos , Lipídeos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Camundongos , Oximas , Polietilenoglicóis , RNA Interferente Pequeno/genética
6.
Drug Discov Today ; 27(9): 2425-2439, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35598703

RESUMO

Cancer is one of the major causes of mortality, accounting for ∼ 9.5 million deaths globally in 2018. The spectrum of conventional treatment for cancer includes surgery, chemotherapy and radiotherapy. Recently, cold plasma therapy surfaced as a novel technique in the treatment of cancer. The FDA approval of the first trial for the use of cold atmospheric plasma (CAP) in cancer therapy in 2019 is evidence of this. This review highlights the mechanisms of action of CAP. Additionally, its applications in anticancer therapy have been reviewed. In summary, this article will introduce the readers to the exciting field of plasma oncology and help them understand the current status and prospects of plasma oncology.


Assuntos
Neoplasias , Gases em Plasma , Humanos
7.
J Therm Anal Calorim ; 147(11): 6337-6348, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34220293

RESUMO

In this work, we demonstrate the enhanced thermal and steric stability of lipid-based formulations in the presence of encapsulated HPPH that have demonstrated potential cancer applications in previously presented in vivo studies. Differential scanning calorimeter (DSC) was used to study the phase transitions, and domain formations, and to qualify the thermodynamic properties associated with change in lipid bilayer behavior due to the presence of PEGylated at varying concentrations and sizes, and the encapsulated HPPH molecules. Thermal instability was quantified by dramatic changes in calculated enthalpy, and the shape of the melting peak or calculated half width of melting peak. This systematic study focused on understanding the effects of varying molecular mass and concentrations of PEG polymers in the photopolymerizable lipid DC8, 9PC lipid bilayer matrix for four weeks at room temperature of 25 °C. The major findings include increased thermal stability of the lipid bilayer due to the presence of PEG-2 K and the HPPH that resulted from the van der Waals forces between various molecular species, and the change in bilayer curvature confirmed via mathematical correlations. It is demonstrated that the encapsulation of therapeutics in lipid formulations can alter their overall thermal behavior, and therefore, it is imperative to consider calorimetric effects while designing lipid-based vaccines. The presented research methodologies and findings presented can predict the stability of lipid-based vaccines that are under development such as COVID-19 during their storage, transport, and distribution.

8.
Int J Pharm ; 606: 120848, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34216762

RESUMO

Photothermal therapy (PTT) is a minimally invasive procedure for treating cancer. The two significant prerequisites of PTT are the photothermal therapeutic agent (PTA) and near-infrared radiation (NIR). The PTA absorbs NIR, causing hyperthermia in the malignant cells. This increased temperature at the tumor microenvironment finally results in tumor cell damage. Nanoparticles play a crucial role in PTT, aiding in the passive and active targeting of the PTA to the tumor microenvironment. Through enhanced permeation and retention effect and surface-engineering, specific targeting could be achieved. This novel delivery tool provides the advantages of changing the shape, size, and surface attributes of the carriers containing PTAs, which might facilitate tumor regression significantly. Further, inclusion of surface engineering of nanoparticles is facilitated through ligating ligands specific to overexpressed receptors on the cancer cell surface. Thus, transforming nanoparticles grants the ability to combine different treatment strategies with PTT to enhance cancer treatment. This review emphasizes properties of PTAs, conjugated biomolecules of PTAs, and the combinatorial techniques for a better therapeutic effect of PTT using the nanoparticle platform.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Neoplasias/terapia , Fototerapia , Terapia Fototérmica , Microambiente Tumoral
9.
Chem Phys Lipids ; 235: 105036, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33412151

RESUMO

The domain of nanomedicine owns a wide-ranging variety of lipid-based drug carriers, and novel nanostructured drug carriersthat are further added to this range every year. The primary goal behind the exploration of any new lipid-based nanoformulation is the improvement of the therapeutic index of the concerned drug molecule along with minimization in the associated side-effects. However, for maintaining a sustained delivery of these intravenously injected lipoidal nanomedicines to the targeted tissues and organ systems in the body, longer circulation in the bloodstream, as well as their stability, are important. After administration, upon recognition as foreign entities in the body, these systems are rapidly cleared by the cells associated with the mononuclear phagocyte system. In order to provide these lipid-based systems with long circulation characteristics, techniques such as coating of the lipoidal surface with an inert polymeric material like polyethylene glycol (PEG) assists in imparting 'stealth properties' to these nanoformulations for avoiding recognition by the macrophages of the immune system. In this review, detailed importance is given to the hydrophilic PEG polymer and the role played by PEG-linked lipid polymers in the field of nanomedicine-based drug carriers. The typical structure and classification of stealth lipids, clinical utility, assemblage techniques, physicochemical characterization, and factors governing the in-vivo performance of the PEG-linked lipids containing formulations will be discussed. Eventually, the novel concept of accelerated blood clearance (ABC) phenomenon associated with the use of PEGylated therapeutics will be deliberated.


Assuntos
Lipídeos/química , Nanomedicina , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos
11.
J Control Release ; 327: 235-265, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-32739524

RESUMO

The diagnosis and treatment of neurological ailments always remain an utmost challenge for research fraternity due to the presence of BBB. The intranasal route appeared as an attractive and alternative route for brain targeting of therapeutics without the intrusion of BBB and GI exposure. This route directly and effectively delivers the therapeutics to different regions of the brain via olfactory and trigeminal nerve pathways. However, shorter drug retention time and mucociliary clearance curtail the efficiency of the intranasal route. The in situ mucoadhesive gel overthrow the limitations of direct nose-to-brain delivery by not only enhancing nasal residence time but also minimizing the mucociliary clearance and enzymatic degradation. This delivery system further improves the nasal absorption as well as bioavailability of drugs in the brain. The in situ mucoadhesive gel is a controlled and sustained release system that facilitates the absorption of various proteins, peptides and other larger lipophilic and hydrophilic moieties. Owing to multiple benefits, in situ gelling system has been widely explored to target the brain via nasal route. However, very few review works are reported which explains the application of in situ nasal gel for brain delivery of CNS acting moieties. Hence, in this piece of work, we have initially discussed the global statistics of neurological disorders reported by WHO and other reputed organizations, nasal anatomy, mechanism and challenges of nose-to-brain drug delivery. The work mainly focused on the use of different stimuli-responsive polymers, specifically thermoresponsive, pH-responsive, and ion triggered systems for the development of an effective and controlled dosage form, i.e., in situ nasal gel for brain targeting of bioactives. We have also highlighted the origin, structure, nature and phase transition behavior of the smart polymers found suitable for nasal administration, including poloxamer, chitosan, EHEC, xyloglucan, Carbopol, gellan gum and DGG along with their application in the treatment of neurological disorders. The article is aimed to gather all the information of the past 10 years related to the development and application of stimuli-responsive in situ nasal gel for brain drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Mucosa Nasal , Administração Intranasal , Encéfalo , Géis
12.
Curr Pharm Des ; 26(36): 4569-4579, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32534562

RESUMO

BACKGROUND: Skin diseases affect all the age groups of people and have an impact on patients' physical, mental, and emotional status. Conventional topical preparation is limited with its efficacy due to low permeation, frequent application, and poor adherence to the therapy for prolong time. OBJECTIVE: The objective of this review article is to address the emerging trends of nanotechnology derived lipidic carrier systems for an effective treatment for skin disorders. METHODOLOGY: Various research and review articles from reputed international journals were referred and compiled. RESULTS AND DISCUSSION: Topical drug delivery systems were found to be more effective than oral and parenteral drug delivery systems for treating skin diseases due to targeted localized applications with reduced side effects. Lipid-based nanoparticles have been found to have the potential in treating skin diseases due to the biocompatibility and the versatility of the lipids. Nanostructured lipid carriers (NLCs) have gained much attention in treating skin diseases due to improved stability of the drugs, enhanced skin permeation, retention, and better therapeutic efficacy. The review summarizes the NLCs characteristics and their application for topical delivery of various therapeutics in skin disorders. NLCs have shown great potential in effective drug delivery for the treatment of psoriasis, dermatitis, bacterial infections, and skin cancer. Its cosmetic application has opened a new area for skincare. Furthermore, safety and clinical status revealed its future commercial acceptability. CONCLUSION: NLCs have been found as effective lipid nanocarriers for the delivery of topical therapeutics.


Assuntos
Nanopartículas , Nanoestruturas , Dermatopatias , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Humanos , Lipídeos , Tamanho da Partícula , Pele/metabolismo , Absorção Cutânea , Dermatopatias/tratamento farmacológico , Dermatopatias/metabolismo
13.
Nanomedicine ; 26: 102176, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32151748

RESUMO

Translation potential of RNA interference nanotherapeutics remains challenging due to in vivo off-target effects and poor endosomal escape. Here, we developed novel polyplexes for controlled intracellular delivery of dicer substrate siRNA, using a light activation approach. Sulfonated polyethylenimines covalently linked to pyropheophorbide-α for photoactivation and bearing modified amines (sulfo-pyro-PEI) for regulated endosomal escape were investigated. Gene knock-down by the polymer-complexed DsiRNA duplexes (siRNA-NPs) was monitored in breast cancer cells. Surprisingly, sulfo-pyro-PEI/siRNA-NPs failed to downregulate the PLK1 or eGFP proteins. However, photoactivation of these cell associated-polyplexes with a 661-nm laser clearly restored knock-down of both proteins. In contrast, protein down-regulation by non-sulfonated pyro-PEI/siRNA-NPs occurred without any laser treatments, indicating cytoplasmic disposition of DsiRNA followed a common intracellular release mechanism. Therefore, sulfonated pyro-PEI holds potential as a unique trap and release light-controlled delivery platform for on-demand gene silencing bearing minimal off target effects.


Assuntos
Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , RNA Helicases DEAD-box/genética , Inativação Gênica , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Ribonuclease III/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Endossomos/efeitos dos fármacos , Feminino , Técnicas de Silenciamento de Genes , Proteínas de Fluorescência Verde/genética , Humanos , Polietilenoimina/química , Polietilenoimina/farmacologia , Polímeros/química , Interferência de RNA , RNA Interferente Pequeno/farmacologia , Quinase 1 Polo-Like
14.
J Control Release ; 321: 372-415, 2020 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-32061621

RESUMO

In last two decades, the lipid nanocarriers have been extensively investigated for their drug targeting efficiency towards the critical areas of the human body like CNS, cardiac region, tumor cells, etc. Owing to the flexibility and biocompatibility, the lipid-based nanocarriers, including nanoemulsion, liposomes, SLN, NLC etc. have gained much attention among various other nanocarrier systems for brain targeting of bioactives. Across different lipid nanocarriers, NLC remains to be the safest, stable, biocompatible and cost-effective drug carrier system with high encapsulation efficiency. Drug delivery to the brain always remains a challenging issue for scientists due to the complex structure and various barrier mechanisms surrounding the brain. The application of a suitable nanocarrier system and the use of any alternative route of drug administration like nose-to-brain drug delivery could overcome the hurdle and improves the therapeutic efficiency of CNS acting drugs thereof. NLC, a second-generation lipid nanocarrier, upsurges the drug permeation across the BBB due to its unique structural properties. The biocompatible lipid matrix and nano-size make it an ideal drug carrier for brain targeting. It offers many advantages over other drug carrier systems, including ease of manufacturing and scale-up to industrial level, higher drug targeting, high drug loading, control drug release, compatibility with a wide range of drug substances, non-toxic and non-irritant behavior. This review highlights recent progresses towards the development of NLC for brain targeting of bioactives with particular reference to its surface modifications, formulations aspects, pharmacokinetic behavior and efficacy towards the treatment of various neurological disorders like AD, PD, schizophrenia, epilepsy, brain cancer, CNS infection (viral and fungal), multiple sclerosis, cerebral ischemia, and cerebral malaria. This work describes in detail the role and application of NLC, along with its different fabrication techniques and associated limitations. Specific emphasis is given to compile a summary and graphical data on the area explored by scientists and researchers worldwide towards the treatment of neurological disorders with or without NLC. The article also highlights a brief insight into two prime approaches for brain targeting, including drug delivery across BBB and direct nose-to-brain drug delivery along with the current global status of specific neurological disorders.


Assuntos
Nanopartículas , Encéfalo , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Lipídeos
15.
J Extracell Vesicles ; 8(1): 1597603, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258878

RESUMO

Biological nanoparticles, including viruses and extracellular vesicles (EVs), are of interest to many fields of medicine as biomarkers and mediators of or treatments for disease. However, exosomes and small viruses fall below the detection limits of conventional flow cytometers due to the overlap of particle-associated scattered light signals with the detection of background instrument noise from diffusely scattered light. To identify, sort, and study distinct subsets of EVs and other nanoparticles, as individual particles, we developed nanoscale Fluorescence Analysis and Cytometric Sorting (nanoFACS) methods to maximise information and material that can be obtained with high speed, high resolution flow cytometers. This nanoFACS method requires analysis of the instrument background noise (herein defined as the "reference noise"). With these methods, we demonstrate detection of tumour cell-derived EVs with specific tumour antigens using both fluorescence and scattered light parameters. We further validated the performance of nanoFACS by sorting two distinct HIV strains to >95% purity and confirmed the viability (infectivity) and molecular specificity (specific cell tropism) of biological nanomaterials sorted with nanoFACS. This nanoFACS method provides a unique way to analyse and sort functional EV- and viral-subsets with preservation of vesicular structure, surface protein specificity and RNA cargo activity.

16.
Photochem Photobiol Sci ; 18(5): 1056-1063, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30608096

RESUMO

A second-generation chlorin-based photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) has shown tremendous therapeutic potential in clinical trials in the treatment of esophageal cancer. Herein, we have developed and validated a bioanalytical method for estimation of HPPH in rat plasma using High Performance Liquid Chromatography (HPLC) with a photo diode array (PDA) detector. The method was applied for carrying out pharmacokinetic study of HPPH. Further pharmacokinetic modeling was carried out to understand the compartment kinetics of HPPH. The developed method was fully validated as per the United States Food and Drug Administration (US-FDA) guidelines for bioanalytical method validation. The linearity of the method was in the range of 250-8000 ng mL-1, and the plasma recovery was found to be 70%. Pharmacokinetic parameters were evaluated and compared via non-compartment analysis and compartment modeling after the intravenous (i.v.) bolus administration in rats using Phoenix WinNonlin 8.0 (Certara™, USA). From the obtained results, we hypothesize that the HPPH complies with two compartmental pharmacokinetic model. Furthermore, it was observed that HPPH has the rapid distribution from the central compartment to peripheral compartment along with slow elimination from peripheral compartment.


Assuntos
Clorofila/análogos & derivados , Fármacos Fotossensibilizantes/farmacocinética , Animais , Clorofila/administração & dosagem , Clorofila/sangue , Clorofila/farmacocinética , Cromatografia Líquida de Alta Pressão , Injeções Intravenosas , Cinética , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/sangue , Ratos , Ratos Wistar
17.
Nanomedicine ; 14(7): 2295-2305, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30059754

RESUMO

Advances in in vivo stability and preferential tumor uptake of cancer nanomedicine are warranted for effective chemotherapy. Here, we describe a novel nanoformulation using an unconventional polymeric tubule-forming phospholipid, DC8,9PC. We report that DC8,9PC transitions to stable vesicles (LNPs) in the presence of PEGylated lipid (DSPE-PEG2000); the resulting DC8,9PC:DSPE-PEG2000 LNPs efficiently included a hydrophobic PDT drug, HPPH. Remarkably, these LNPs incorporated unusually high DSPE-PEG2000 concentrations; LNP10-HPPH and LNP20-HPPH (10 & 20 mol% PEGylated lipid, respectively) exhibited >90% serum stability at 37 °C. Increased PEGylation in the LNPs correlated with enhanced tumor accumulation in intravenously injected HT29 tumor mouse xenographs. Colon-26 bearing BALB/c mice, intravenously injected with LNP20-HPPH showed superior PDT efficacy and animal survival (no tumor recurrence up to 100 days) as compared to a formulation currently used in clinical trials. Taken together, we present a simple stealth binary lipid nanosystem with enhanced efficiency of tumor accumulation and superior therapeutic efficacy.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Fosfolipídeos/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Polímeros/química , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Portadores de Fármacos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
ACS Appl Mater Interfaces ; 9(38): 32621-32634, 2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28876042

RESUMO

Solid-state nanopores within graphene-based materials are on the brink of fundamentally changing the sensing of desired bioanalytes through ion trafficking across nanoporous membranes. Here, we report on a two-electrode electrochemical biosensor comprised of a graphene oxide-polycarbonate track-etched nanosieve platform for the rapid and sensitive detection of the Human Immunodeficiency Virus Type 1 (HIV-1) envelope glycoprotein ectodomain (gp140MS). We have covalently linked an engineered high-affinity one-domain soluble CD4 fused to a human domain targeting HIV-1 coreceptor binding site and ferrocene (Fc) (2Dm2m) to the nanosieve platform. An exponential decrease in the ionic current resulted from a partial blockade of the nanosieve due to the specific interactions of gp140MS with the 2Dm2m protein, which was immobilized on the nanosieve platform by biolinkage as a function of applied voltages of 0.1-2.0 V. There was no change in current when a nonspecific antigen bovine serum albumin was tested under identical conditions. This platform had high sensitivity, and when the receptor-binding phenomenon was tested to identify the minimum concentration of target analyte, the lowest detection limit was as short as 8.3 fM and with sensitivity and response times of 0.87 mA mM-1 cm-1 and 12 s, respectively. In addition to this remarkable sensitivity, our nanobiorecognition platform has the advantage of superior stability due to the few layered graphene oxide laminates. It also exhibits exceptional biomolecule binding and higher reusability, sustainability, and ease of fabrication in a soft mechanism. Real samples of HIV positive and negative patients were successfully tested to confirm the virus by the developed platform. To the best of our knowledge, this is the first time prosperous pervious remembrance surface has been employed in a nanobiosensing application. In light of the recent great trend of using graphene-based nanopore surfaces created by sophisticated ion-beam methods in sensing and sequencing, this hybrid-surface nanolayer fabricated by the simple vacuum filtration of a few layered graphene oxide laminates may serve as a good alternative in terms of ease of fabrication without expensive instrumental prerequisites.


Assuntos
Grafite/química , Técnicas Biossensoriais , Técnicas Eletroquímicas , HIV , Infecções por HIV , Humanos , Óxidos , Cimento de Policarboxilato , Proteínas do Envelope Viral
19.
Methods Mol Biol ; 1632: 241-253, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28730444

RESUMO

RNAi-based therapeutic approaches to combat cancer and other diseases are currently an area of great interest. However, practical applications of this approach rely on optimal tools to carry and deliver siRNA to the desired site. Oxime ether lipids (OELs) are a class of molecules among other various carriers being examined for siRNA delivery. OELs, relatively new candidates, belong to a class of non-glycerol based lipids and have begun to claim their place as an siRNA delivery carrier in the field of RNAi therapy. Chemical synthesis steps of OELs are considered relatively simple with the ability to modify the functionalities as desired. OEL-siRNA complexes can be assembled in the presence of serum-containing buffers (or cell culture media) and recent data from our and other groups have demonstrated that OELs are viable carriers for siRNA delivery in the cell culture systems. In this chapter, we provide the details of experimental protocols routinely used in our laboratory to examine OEL-siRNA complexes including their assembly, stability, and transfection efficiencies.


Assuntos
Éter , Lipídeos , Oximas , RNA Interferente Pequeno/genética , Transfecção/métodos , Linhagem Celular Tumoral , Éter/química , Expressão Gênica , Inativação Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Lipossomos/química , Oximas/química , Relação Estrutura-Atividade
20.
Artigo em Inglês | MEDLINE | ID: mdl-27391314

RESUMO

Nano-biosensors are excellent monitoring tools for rapid, specific, sensitive, inexpensive, in-field, on-line, and/or real-time detection of pathogens in foods, soil, air, and water samples. A variety of nano-materials (metallic, polymeric, and/or carbon-based) were employed to enhance the efficacy, efficiency, and sensitivity of these nano-biosensors, including graphene-based materials, especially graphene oxide (GO)-based materials. GO bears many oxygen-bearing groups, enabling ligand conjugation at the high density critical for sensitive detection. We have fabricated GO-modified nano-porous polycarbonate track-etched (PCTE) membranes that were conjugated to an Escherichia coli-specific antibody (Ab) and used to detect E. coli. The random distribution of nanopores on the PCTE membrane surface and the bright coating of the GO onto the membrane were confirmed by scanning electron microscope. Anti-E. coli ß-gal Abs were conjugated to the GO surface via 1-ethyl-3,3-dimethylaminopropyl carbodiimide hydrochloride-N-hydroxysuccinimide chemistry; antibody coating was confirmed by the presence of a characteristic IR peak near 1600cm(-1). A non-corresponding Ab (anti-Pseudomonas) was used as a negative control under identical conditions. When E. coli interacted anti-E.coli ß-gal with Ab-coated GO-nano-biosensor units, we observed a clear shift in the IR peak from 3373.14 to 3315cm(-1); in contrast, we did not observe any shift in IR peaks when the GO unit was coated with the non-corresponding Ab (anti-Pseudomonas). Therefore, the detection of E. coli using the described GO-nano-sensor unit is highly specific, is highly selective and can be applied for real-time monitoring of E. coli with a detection limit between 100µg/mL and 10µg/mL, similar to existing detection systems.


Assuntos
Escherichia coli/isolamento & purificação , Grafite/química , Membranas Artificiais , Nanoporos , Cimento de Policarboxilato/química , Ouro/química , Limite de Detecção , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier
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