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1.
Cureus ; 16(3): e55783, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586779

RESUMO

Objective The objective was to evaluate the modified frailty index as a predictor of early (within 30 days) postoperative complications in total joint arthroplasty patients, in a low middle-income country. Material and methods A cross-sectional study was carried out which included patients with ages ranging from 23 to 86 years, who underwent elective primary Total Hip or Knee Arthroplasties (TKA or THA) between December 2021 and February 2023. Modified frailty index (mFI-5) was calculated and 30-day morbidity and mortality were recorded. Post-operative complications were categorized as either surgical or medical and recorded. Results A total of 175 patients were included, amongst whom the majority were females (68.6%, n=120) and the mean age was 60.5 ± 13.2 years. 85 patients (48.6%) had a mFI-5 score of one while 48 patients (27.4%) had a score of two. Superficial surgical site infection was the most common complication overall in 6 patients (3.4%); however, no case of prosthetic joint infection was noted. Deep vein thrombosis (DVT) was the most common medical complication (1.7%, n=3). 5 patients (2.9%) required re-admission and two mortalities were recorded within the 30-day interval. A significant association was noted between post-operative surgical complications and mFI-5 score (p-value = < 0.001), with the risk of complications increasing with a higher mFI-5 score. Smoking was noted to be a risk factor for post-operative medical complications as well as 30-day mortality. Conclusion The current study shows that the mFI-5 index can effectively be used as a predictor of postoperative complications in the South Asian region such as Pakistan. This should be calculated routinely and can be used as a tool for pre-operative assessment and counseling.

2.
Nitric Oxide ; 147: 42-50, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631610

RESUMO

Nitric oxide (NO) donating drugs such as organic nitrates have been used to treat cardiovascular diseases for more than a century. These donors primarily produce NO systemically. It is however sometimes desirable to control the amount, location, and time of NO delivery. We present the design of a novel pH-sensitive NO release system that is achieved by the synthesis of dipeptide diphenylalanine (FF) and graphene oxide (GO) co-assembled hybrid nanosheets (termed as FF@GO) through weak molecular interactions. These hybrid nanosheets were characterised by using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, zeta potential measurements, X-ray photoelectron spectroscopy, scanning and transmission electron microscopies. The weak molecular interactions, which include electrostatic, hydrogen bonding and π-π stacking, are pH sensitive due to the presence of carboxylic acid and amine functionalities on GO and the dipeptide building blocks. Herein, we demonstrate that this formulation can be loaded with NO gas with the dipeptide acting as an arresting agent to inhibit NO burst release at neutral pH; however, at acidic pH it is capable of releasing NO at the rate of up to 0.6 µM per minute, comparable to the amount of NO produced by healthy endothelium. In conclusion, the innovative conjugation of dipeptide with graphene can store and release NO gas under physiologically relevant concentrations in a pH-responsive manner. pH responsive NO-releasing organic-inorganic nanohybrids may prove useful for the treatment of cardiovascular diseases and other pathologies.


Assuntos
Grafite , Nanoestruturas , Óxido Nítrico , Grafite/química , Concentração de Íons de Hidrogênio , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Nanoestruturas/química , Humanos , Dipeptídeos/química , Fenilalanina/química , Fenilalanina/análogos & derivados
3.
Chembiochem ; 25(10): e202300867, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38551557

RESUMO

Peptides have become an indispensable tool in engineering of multifunctional nanostructure platforms for biomedical applications such as targeted drug and gene delivery, imaging and biosensing. They can be covalently incorporated into a variety of nanoparticles (NPs) including polymers, metallic nanoparticles, and others. Using different bioconjugation techniques, multifunctional peptide-modified NPs can be formulated to produce therapeutical and diagnostic platforms offering high specificity, lower toxicity, biocompatibility, and stimuli responsive behavior. Targeting peptides can direct the nanoparticles into specific tissues for targeted drug and gene delivery and imaging applications due to their specificity towards certain receptors. Furthermore, due to their stimuli-responsive features, they can offer controlled release of therapeutics into desired sites of disease. In addition, peptide-based biosensors and imaging agents can provide non-invasive detection and monitoring of diseases including cancer, infectious diseases, and neurological disorders. In this review, we covered the design and formulation of recent peptide-based NP platforms, as well as their utilization in in vitro and in vivo applications such as targeted drug and gene delivery, targeting, sensing, and imaging applications. In the end, we provided the future outlook to design new peptide conjugated nanomaterials for biomedical applications.


Assuntos
Técnicas Biossensoriais , Nanopartículas , Peptídeos , Técnicas Biossensoriais/métodos , Peptídeos/química , Humanos , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Animais
4.
Biochim Biophys Acta Gen Subj ; 1868(4): 130577, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301858

RESUMO

F-box only protein 8 (FBXO8) is a recently identified member of the F-box proteins, showcasing its novelty in this protein family. Extensive research has established FBXO8's role as a tumor suppressor in various cancers, including hepatocellular carcinoma, and colorectal cancer, Nevertheless, its functional, mechanistic, and prognostic roles in primary and metastatic breast cancer, particularly in different molecular subtypes of breast cancer, various stages, as well as its potential implications in immunotherapy, tumor microenvironment, and prognostic survival among breast cancer patients, remain unexplored. In this article, we employed a multi-dimensional investigation leveraging TCGA, TIMER, TISIDB, STRING, MEXPRESS, UALCAN, and cBioPortal databases to explore the underlying suppression mechanism of FBXO8 in breast cancer. FBXO8 negatively correlates with MYC, NOTCH, WNT and inflammatory signaling pathways in breast tumor microenvironment. Furthermore we conducted RT-PCR, western blot, cell proliferation, cell migration, and mRNA target gene RT-PCR analyses to elucidate the role of FBXO8 in breast cancer progression. Mechanistically, PTEN and FBXW7 expression were down-regulated and MYC, IL10, IL6, NOTCH1, WNT6 mRNA expressions were up-regulated in FBXO8 knockdown cell lines. c-MYC silenced cells showed an increase in FBXO8 protein level, which suggests a negative feedback loop between FBXO8 and c-MYC to control breast cancer metastasis. These findings illuminate the novel role of FBXO8 as a prognostic and therapeutic target across different molecular subtypes of breast cancer. Finally, through the utilization of virtual screening and Molecular Dynamics simulations, we successfully identified two FDA-approved medications, Ledipasvir and Paritaprevir, that demonstrated robust binding capabilities and interactions with FBXO8.


Assuntos
Neoplasias da Mama , Neoplasias Hepáticas , Feminino , Humanos , Biomarcadores , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Prognóstico , RNA Mensageiro , Microambiente Tumoral
5.
J Med Case Rep ; 17(1): 538, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082359

RESUMO

BACKGROUND: Schwannomas are solitary well-circumscribed encapsulated benign tumors that exhibit Schwann cell differentiation, and arise directly from myelinated peripheral or central nerves. Although they are usually asymptomatic and found incidentally, schwannomas can cause symptoms due to compression of nearby structures which, depending on the location, can make clinical presentations widely variable. Despite their rarity, schwannomas have been documented in a number of locations including the limbs, cerebellopontine angle, posterior mediastinum, and, far more infrequently, the lungs. CASE PRESENTATION: In this article, we report an incidental finding of an intrapulmonary schwannoma in a 59-year-old Pakistani woman who was grossly asymptomatic upon presentation to the cardiothoracic surgery clinic. An [18F]fluorodeoxyglucose positron emission tomography/computed tomography scan revealed a lobulated soft-tissue lesion measuring 23 mm × 23 mm in the lower lobe of the right lung. A computed tomography-guided core biopsy of the mass was performed, which revealed a benign spindle cell lesion based on histopathological examination and immunohistochemical staining. The mass was surgically resected via a right lower lobectomy, and subsequently confirmed to be an encapsulated neoplastic lesion composed of well-differentiated Schwann cells. There were no short- or long-term complications, morbidities, or recurrences based on 1-year follow-up. CONCLUSION: This report underscores the predominantly asymptomatic nature of schwannomas and reemphasizes the efficacy of surgical resection as a safe and curative procedure for a tumor of this nature. Albeit very rare, intrapulmonary schwannomas can be considered a differential diagnosis when encountering solitary asymptomatic pulmonary nodules or masses.


Assuntos
Pulmão , Neurilemoma , Feminino , Humanos , Pessoa de Meia-Idade , Pulmão/diagnóstico por imagem , Pulmão/patologia , Mediastino/patologia , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18
6.
Nat Commun ; 14(1): 8492, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129391

RESUMO

Coacervate droplets are promising protocell models because they sequester a wide range of guest molecules and may catalyze their conversion. However, it remains unclear how life's building blocks, including peptides, could be synthesized from primitive precursor molecules inside such protocells. Here, we develop a redox-active protocell model formed by phase separation of prebiotically relevant ferricyanide (Fe(CN)63-) molecules and cationic peptides. Their assembly into coacervates can be regulated by redox chemistry and the coacervates act as oxidizing hubs for sequestered metabolites, like NAD(P)H and gluthathione. Interestingly, the oxidizing potential of Fe(CN)63- inside coacervates can be harnessed to drive the formation of new amide bonds between prebiotically relevant amino acids and α-amidothioacids. Aminoacylation is enhanced in Fe(CN)63-/peptide coacervates and selective for amino acids that interact less strongly with the coacervates. We finally use Fe(CN)63--containing coacervates to spatially control assembly of fibrous networks inside and at the surface of coacervate protocells. These results provide an important step towards the prebiotically relevant integration of redox chemistry in primitive cell-like compartments.


Assuntos
Células Artificiais , Células Artificiais/química , Peptídeos , Oxirredução , Aminoácidos , Amidas
7.
Chemistry ; 29(50): e202301159, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37310801

RESUMO

Biochemical reactions occurring in highly crowded cellular environments require different means of control to ensure productivity and specificity. Compartmentalization of reagents by liquid-liquid phase separation is one of these means. However, extremely high local protein concentrations of up to 400 mg/ml can result in pathological aggregation into fibrillar amyloid structures, a phenomenon that has been linked to various neurodegenerative diseases. Despite its relevance, the process of liquid-to-solid transition inside condensates is still not well understood at the molecular level. We thus herein use small peptide derivatives that can undergo both liquid-liquid and subsequent liquid-to-solid phase transition as model systems to study both processes. Using solid-state nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM), we compare the structure of condensed states of leucine, tryptophan and phenylalanine containing derivatives, distinguishing between liquid-like condensates, amorphous aggregates and fibrils, respectively. A structural model for the fibrils formed by the phenylalanine derivative was obtained by an NMR-based structure calculation. The fibrils are stabilised by hydrogen bonds and side-chain π-π interactions, which are likely much less pronounced or absent in the liquid and amorphous state. Such noncovalent interactions are equally important for the liquid-to-solid transition of proteins, particularly those related to neurodegenerative diseases.


Assuntos
Amiloide , Peptídeos , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de Proteína , Modelos Moleculares , Espectroscopia de Ressonância Magnética , Amiloide/química , Fenilalanina
8.
Ann Med Surg (Lond) ; 81: 104219, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35957649

RESUMO

Background: The COVID-19 pandemic has significantly affected the lives of healthcare workers due to the frontline nature of their work. Their hard work and sacrifice have forged new perceptions of healthcare workers. These changes may potentially influence students' interest in medicine. This study explores how the COVID-19 pandemic has affected premedical students' decisions to pursue medicine as a career. Methods: A cross-sectional study using a self-designed online questionnaire was carried out amongst pre-medical students across Pakistan. Results: A total of 1695 students from 93 public and private schools filled in the survey. After the onset of the COVID-19 pandemic, significantly more pre-medical students want to pursue medicine (60.7%-62.9%) and less are unsure (20.2%-17%). Students are significantly more likely to be motivated to pursue medicine due to altruistic benefits to society (57% vs. 62.7%) and be deterred by the risk of contracting infections on duty (10%-14.6%). There is a minor but significant increase in the popularity of internal medicine (17.1%-18.9%), public health (4.1% vs. 5.7%), emergency medicine (3.8% vs. 5.7%), pediatrics (3.8% vs. 4.7%), and radiology (2.1% vs. 2.9%). Most pre-medical students felt that doctors routinely undergo physical and emotional turmoil (84%). Conclusions: Although awareness of hardships faced by medical professionals has increased, motivation to pursue medicine has grown. Through understanding trends in the motivations of students to pursue medicine, medical schools can accommodate the expectations of incoming students and reach out to potential applicants.

9.
Adv Mater ; 34(34): e2202913, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35796384

RESUMO

Coacervates droplets have long been considered as potential protocells to mimic living cells. However, these droplets lack a membrane and are prone to coalescence, limiting their ability to survive, interact, and organize into higher-order assemblies. This work shows that tyrosine-rich peptide conjugates can undergo liquid-liquid phase separation in a well-defined pH window and transform into stable membrane-enclosed protocells by enzymatic oxidation and cross-linking at the liquid-liquid interface. The oxidation of the tyrosine-rich peptides into dityrosine creates a semipermeable, flexible membrane around the coacervates with tunable thickness, which displays strong intrinsic fluorescence, and stabilizes the coacervate protocells against coalescence. The membranes have an effective molecular weight cut-off of 2.5 kDa, as determined from the partitioning of small dyes and labeled peptides, RNA, and polymers into the membrane-enclosed coacervate protocells. Flicker spectroscopy reveals a membrane bending rigidity of only 0.1kB T, which is substantially lower than phospholipid bilayers despite a larger membrane thickness. Finally, it is shown that enzymes can be stably encapsulated inside the protocells and be supplied with substrates from outside, which opens the way for these membrane-bound compartments to be used as molecularly crowded artificial cells capable of communication or as a vehicle for drug delivery.


Assuntos
Células Artificiais , Células Artificiais/química , Peptídeos , Polímeros , RNA , Tirosina
10.
World J Surg ; 46(9): 2063-2072, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35538319

RESUMO

BACKGROUND: While gender disparities in surgery are documented worldwide, it is unclear to what extent women consider surgery as a career before embarking on their medical school journey. This study aimed to report the percentage of pre-medical women in Pakistan who intend to eventually specialize in surgery and assess the factors motivating and deterring this decision. METHODS: An online survey was conducted among female pre-medical (high school) students across Pakistan. Multivariable logistic regression was performed to determine motivating and deterring factors associated with the intention to pursue surgery. RESULTS: Out of 1219 female high-school students, 764 (62.7) intended to join medical school. Among these 764, only 9.8% reported an exclusive intent to pursue surgery, while just 20.3% reported considering other specialties in addition to surgery. Significant motivators to pursue surgery exclusively were the intellectual satisfaction of pursuing surgery (adjusted odds ratio: 2.302), having opportunities to travel internationally for work (2.300) and use cutting-edge technology (2.203), interest in the specialty of surgery (2.031), the social prestige of becoming a surgeon (1.910), and considering one's personality well-suited to surgery (1.888). Major deterrents included the lack of interest in surgery (adjusted odds ratio: 3.812), surgical education and training being too difficult (2.440) and lengthy (1.404), and the risk of aggressive behavior from patients (2.239). CONCLUSION: Even before entering medical school, most female pre-medical students have already decided against considering a future surgical career. Deterrents likely stem from women being pressured to conform to deep-seated societal expectations to dedicate their time and energy to domestic responsibilities.


Assuntos
Estudantes de Medicina , Escolha da Profissão , Estudos Transversais , Feminino , Humanos , Intenção , Paquistão , Inquéritos e Questionários
11.
JTO Clin Res Rep ; 3(2): 100284, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35199056

RESUMO

Adenoid cystic carcinoma, also known as cylindroma, is one of the rare and unexplored clinical presentations of lung cancer, for which existing knowledge is scarce. This case report discusses a presentation of this tumor in the right lung, which subsequently extended to the left atrium through the right superior pulmonary vein. The extension of this rare tumor into the left atrium makes this case both uniquely distinctive and clinically relevant. The management strategy opted for this case was a right posterolateral thoracotomy and right pneumonectomy with partial resection of the left atrium. The desired outcome of this report is to shed light on the unusual clinical pathophysiology, register its atypical extensions, and navigate surgeons who may encounter this manifestation in the future.

12.
Semin Cancer Biol ; 86(Pt 3): 693-705, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34118405

RESUMO

Past few years have seen a paradigm shift towards ecofriendly, green and biological fabrication of metal nanoparticles (MNPs) for diverse nanomedicinal applications especially in cancer nanotheranostics. Besides, the well-known green synthesis methods of plant materials, the potential of the microbial world (bacteria, fungi, alga, etc.) in biofabrication is equally realized. Biomolecules and enzymes in the microbial cells are capable of catalyzing the biosynthesis process. These microbial derived inorganic nanoparticles have been frequently evaluated as potential agents in cancer therapies revealing exciting results. Through, cellular and molecular pathways, these microbial derived nanoparticles are capable of killing the cancer cells. Considering the recent developments in the anticancer applications of microbial derived inorganic MNPs, a dire need was felt to bring the available information to a single document. This manuscript reviews not only the mechanistic aspects of the microbial derived MNPs but also include the diverse mechanisms that governs their anticancer potential. Besides, an updated literature review is presented that includes studies of 2019-onwards.


Assuntos
Nanopartículas Metálicas , Neoplasias , Humanos , Nanopartículas Metálicas/uso terapêutico , Fungos/metabolismo , Bactérias/metabolismo , Neoplasias/tratamento farmacológico
13.
Nat Chem ; 13(11): 1046-1054, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34645986

RESUMO

Liquid-liquid phase separation of disordered proteins has emerged as a ubiquitous route to membraneless compartments in living cells, and similar coacervates may have played a role when the first cells formed. However, existing coacervates are typically made of multiple macromolecular components, and designing short peptide analogues capable of self-coacervation has proven difficult. Here we present a short peptide synthon for phase separation, made of only two dipeptide stickers linked via a flexible, hydrophilic spacer. These small-molecule compounds self-coacervate into micrometre-sized liquid droplets at sub-millimolar concentrations, which retain up to 75 wt% water. The design is general and we derive guidelines for the required sticker hydrophobicity and spacer polarity. To illustrate their potential as protocells, we create a disulfide-linked derivative that undergoes reversible compartmentalization controlled by redox chemistry. The resulting coacervates sequester and melt nucleic acids, and act as microreactors that catalyse two different anabolic reactions yielding molecules of increasing complexity. This provides a stepping stone for new coacervate-based protocells made of single peptide species.


Assuntos
Extração Líquido-Líquido/métodos , Peptídeos/química , Catálise , Interações Hidrofóbicas e Hidrofílicas , Oxirredução
14.
Chem Soc Rev ; 50(6): 3690-3705, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33616129

RESUMO

Coacervates are condensed liquid-like droplets formed by liquid-liquid phase separation of molecules through multiple weak associative interactions. In recent years it has emerged that not only long polymers, but also short peptides are capable of forming simple and complex coacervates. The coacervate droplets they form act as compartments that sequester and concentrate a wide range of solutes, and their spontaneous formation make coacervates attractive protocell models. The main advantage of peptides as building blocks lies in the functional diversity of the amino acid residues, which allows for tailoring of the peptide's phase separation propensity, their selectivity in guest molecule uptake and the physicochemical and catalytic properties of the compartments. The aim of this tutorial review is to illustrate the recent developments in the field of peptide-based coacervates in a systematic way and to deduce the basic requirements for both simple and complex coacervation of peptides. We review a selection of peptide coacervates that illustrates the essentials of phase separation, the limitations, and the properties that make peptide coacervates biomimetic protocells. Finally, we provide some perspectives of this novel research field in the direction of active droplets, moving away from thermodynamic equilibrium.


Assuntos
Células Artificiais/química , Biomimética , Peptídeos/química , Catálise , Nucleotídeos/química , Polietilenoglicóis/química
15.
ACS Appl Bio Mater ; 4(12): 8522-8535, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-35005954

RESUMO

An alarming increase in antibiotic-resistant bacterial strains is driving clinical demand for new antibacterial agents. One of the oldest antimicrobial agents is elementary silver (Ag), which has been used for thousands of years. Even today, elementary Ag is used for medical purposes such as treating burns, wounds, and microbial infections. In consideration of the effectiveness of elementary Ag, the present researchers generated effective antibacterial/antibiofilm agents by combining elementary Ag with biocompatible ultrashort peptide compounds. The innovative antibacterial agents comprised a hybrid peptide bound to Ag nanoparticles (IVFK/Ag NPs). These were generated by photoionizing a biocompatible ultrashort peptide, thus reducing Ag ions to form Ag NPs with a diameter of 6 nm. The IVFK/Ag NPs demonstrated promising antibacterial/antibiofilm activity against reference Gram-positive and Gram-negative bacteria compared with commercial Ag NPs. Through morphological changes in Escherichia coli and Staphylococcus aureus, we proposed that the mechanism of action for IVFK/Ag NPs derives from their ability to disrupt bacterial membranes. In terms of safety, the IVFK/Ag NPs demonstrated biocompatibility in the presence of human dermal fibroblast cells, and concentrations within the minimal inhibitory concentration had no significant effect on cell viability. These results demonstrated that hybrid peptide/Ag NPs hold promise as a biocompatible material with strong antibacterial/antibiofilm properties, allowing them to be applied across a wide range of applications in tissue engineering and regenerative medicine.


Assuntos
Nanopartículas Metálicas , Prata , Antibacterianos/farmacologia , Bactérias/metabolismo , Biofilmes , Escherichia coli , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos , Nanopartículas Metálicas/química , Peptídeos/farmacologia , Prata/farmacologia
16.
ACS Biomater Sci Eng ; 4(6): 2046-2052, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-33445275

RESUMO

Hydrogels self-assembled by biologically based building blocks including peptides and proteins can be used as an ideal drug delivery platform and present great promise for biomedical applications. Herein, photodynamic antitumor therapy based on injectable N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF)/poly-l-lysine (PLL) hydrogels was achieved by encapsulation of the photosensitive drug Chlorin e6 (Ce6), as the hydrogels exhibit multiple favorable therapeutic features, including shear-thinning and self-healing properties, good biocompatibility, and perfect biodegradability. Such injectable hydrogels are shown to be well-suited for local injection and sustained drug delivery at the tumor site, especially toward therapy of superficial tumors. In vivo therapeutic results show that the tumor growth can be efficiently inhibited, especially under the strategy "once injection, multiple-treatments". During the whole treatment period, no detectable toxicity or damages to normal organs are observed. Therefore, the injectable hydrogels can be applied as a promising delivery platform for therapy of superficial tumors.

17.
J Am Chem Soc ; 139(5): 1921-1927, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28103663

RESUMO

Photothermal agents can harvest light energy and convert it into heat, offering a targeted and remote-controlled way to destroy carcinomatous cells and tissues. Inspired by the biological organization of polypeptides and porphyrins in living systems, here we have developed a supramolecular strategy to fabricate photothermal nanodots through peptide-modulated self-assembly of photoactive porphyrins. The self-assembling nature of porphyrins induces the formation of J-aggregates as substructures of the nanodots, and thus enables the fabrication of nanodots with totally inhibited fluorescence emission and singlet oxygen production, leading to a high light-to-heat conversion efficiency of the nanodots. The peptide moieties not only provide aqueous stability for the nanodots through hydrophilic interactions, but also provide a spatial barrier between porphyrin groups to inhibit the further growth of nanodots through the strong π-stacking interactions. Thermographic imaging reveals that the conversion of light to heat based on the nanodots is efficient in vitro and in vivo, enabling the nanodots to be applied for photothermal acoustic imaging and antitumor therapy. Antitumor therapy results show that these nanodots are highly biocompatible photothermal agents for tumor ablation, demonstrating the feasibility of using bioinspired nanostructures of self-assembling biomaterials for biomedical photoactive applications.


Assuntos
Antineoplásicos/farmacologia , Nanoestruturas/química , Peptídeos/farmacologia , Fototerapia , Porfirinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos , Estrutura Molecular , Tamanho da Partícula , Peptídeos/química , Processos Fotoquímicos , Porfirinas/química , Relação Estrutura-Atividade , Propriedades de Superfície
18.
Adv Mater ; 29(12)2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28060418

RESUMO

Tremendous interest in self-assembly of peptides and proteins towards functional nanomaterials has been inspired by naturally evolving self-assembly in biological construction of multiple and sophisticated protein architectures in organisms. Self-assembled peptide and protein nanoarchitectures are excellent promising candidates for facilitating biomedical applications due to their advantages of structural, mechanical, and functional diversity and high biocompability and biodegradability. Here, this review focuses on the self-assembly of peptides and proteins for fabrication of phototherapeutic nanomaterials for antitumor photodynamic and photothermal therapy, with emphasis on building blocks, non-covalent interactions, strategies, and the nanoarchitectures of self-assembly. The exciting antitumor activities achieved by these phototherapeutic nanomaterials are also discussed in-depth, along with the relationships between their specific nanoarchitectures and their unique properties, providing an increased understanding of the role of peptide and protein self-assembly in improving the efficiency of photodynamic and photothermal therapy.

19.
Adv Mater ; 28(6): 1031-43, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26273821

RESUMO

Elegant self-assembling complexes by the combination of proteins/peptides with functional chromophores are decisively responsible for highly efficient light-harvesting and energy transfer in natural photosynthetic systems. Mimicking natural light-harvesting complexes through synthetic peptides is attractive due to their advantanges of programmable primary structure, tunable self-assembly architecture and easy availability in comparison to naturally occuring proteins. Here, an overview of recent progresses in the area of biomimetic light-harvesting nanoarchitectonics based on peptide-modulated self-assembly of chromophores is provided. Adjusting the organization of chromophores, either by creating peptide-chromophore conjugates or by the non-covalent assembly of peptides and chromophores are highlighted. The light-harvesting properties, especially the energy transfer of the biomimetic complexes are critically discussed. The applications of such complexes in the mineralization of inorganic nanoparticles, generation of molecular hydrogen and oxygen, and photosynthesis of bioactive molecules are also included.


Assuntos
Biomimética , Complexos de Proteínas Captadores de Luz/química , Nanotecnologia/métodos , Peptídeos/química , Elétrons , Transferência de Energia , Transferência Ressonante de Energia de Fluorescência , Fulerenos/química , Hidrogênio/química , Luz , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Oxigênio/química , Fotossíntese , Porfirinas/química , Energia Solar , Eletricidade Estática
20.
J Nanosci Nanotechnol ; 15(12): 10141-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26682460

RESUMO

Nanoengineering of anticancer therapeutic drugs including photosensitizers is highly desired and extremely required for improved therapeutic efficacy. It remains a formidable challenge to achieve nanostructured colloidal particles directly starting from hydrophobic drugs due to their hydrophobic nature and ready aggregation in aqueous ambient. In this work, we report a facile method for a one-pot preparation of hydrophobic photosensitizer nanoparticles by coating with different types of polyelectrolyte as stabilizing agents. Regardless of negatively or positively charged polyelectrolyte used, including Poly-L-lysine (PLL, MW = 15 k-30 k), PLL (MW = 30 k-70 k), heparin, and hyaluronic acid (HA), the hydrophobic photosensitizer BDEA (2,5-Bis(4-(diethylamino)benzylidene)cyclopentanone) as a model drug can be readily manipulated into stable and well-dispersed nanoparticles with size of average 120 nm. Stabilization presumably contributes to electrostatic repulsion of the adsorbed polyelectrolyte layer onto nanoparticles. Their anticancer activity against the HeLa cell line shows that the endocytic internalization of these nanosystems is associated with antiproliferative effects after irradiation with visible light. The one-step preparation strategy may be an alternative approach for the design of nano-formulations of hydrophobic photosensitive drugs, presenting a potential for photodynamic antitumor therapy.


Assuntos
Antineoplásicos/síntese química , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanotecnologia
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