RESUMO
The coronavirus disease 2019 (COVID-19) has dramatically challenged the healthcare system of almost all countries. The authorities are struggling to minimize the mortality along with ameliorating the economic downturn. Unfortunately, until now, there has been no promising medicine or vaccine available. Herein, we deliver perspectives of nanotechnology for increasing the specificity and sensitivity of current interventional platforms toward the urgent need of quickly deployable solutions. This review summarizes the recent involvement of nanotechnology from the development of a biosensor to fabrication of a multifunctional nanohybrid system for respiratory and deadly viruses, along with the recent interventions and current understanding about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Nanotecnologia/tendências , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Técnicas Biossensoriais , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pandemias , Tratamento Farmacológico da COVID-19RESUMO
Integrating the concept of biodegradation and light-triggered localized therapy in a functional nanoformulation is the current approach in onco-nanomedicine. Morphology control with an enhanced photothermal response, minimal toxicity, and X-ray attenuation of polymer-based nanoparticles is a critical concern for image-guided photothermal therapy. Herein, we describe the simple design of cost-effective and degradable polycaprolactone-based plasmonic nanoshells for the integrated photothermolysis as well as localized imaging of cancer cells. The gold-deposited polycaprolactone-based plasmonic nanoshells (AuPCL NS) are synthesized in a scalable and facile way under ambient conditions. The synthesized nanoshells are monodisperse, fairly stable, and highly inert even at five times (250 µg/mL) the therapeutic concentration in a week-long test. AuPCL NS are capable of delivering standalone photothermal therapy for the complete ablation of cancer cells without using any anticancerous drugs and causing toxicity. It delivers the same therapeutic efficacy to different cancer cell lines, irrespective of their chemorefractory status and also works as a potential computed tomography contrast agent for the integrated imaging-directed photothermal cancer therapy. High biocompatibility, degradability, and promising photothermal efficacy of AuPCL NS are attractive aspects of this report that could open new horizons of localized plasmonic photothermal therapy for healthcare applications.
Assuntos
Nanomedicina/economia , Nanomedicina/métodos , Nanoconchas/uso terapêutico , Fototerapia/economia , Fototerapia/métodos , Animais , Linhagem Celular Tumoral , Análise Custo-Benefício , Humanos , Hipertermia Induzida , Polímeros/químicaRESUMO
In this work, facile synthesis and application of targeted, dual therapeutic gold nanorods-liposome (GNR-Lipos) nanohybrid for imaging guided photothermal therapy and chemotherapy is investigated. The dual therapeutic GNR-Lipos nanohybrid consists of GNR supported, and doxorubicin (DOX) loaded liposome. GNRs not only serve as a photothermal agent and increase the drug release in intracellular environment of cancer cells, but also provide mechanical strength to liposomes by being decorated both inside and outside of bilayer surfaces. The designed nanohybrid shows a remarkable response for synergistic chemophotothermal therapy compared to only chemotherapy or photothermal therapy. The NIR response, efficient uptake by the cells, disintegration of GNR-Lipos nanohybrid, and synergistic therapeutic effect of photothermal and chemotherapy over breast cancer cells MDA-MB-231 are studied for the better development of a biocompatible nanomaterial based multifunctional cancer theranostic agent.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Doxorrubicina/análogos & derivados , Ouro/farmacologia , Nanotubos/química , Nanomedicina Teranóstica/métodos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Preparações de Ação Retardada/química , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Ouro/química , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Nanotubos/ultraestrutura , Imagem Óptica/métodos , Fototerapia/métodos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoglicóis/farmacologiaRESUMO
Enhanced biocompatibility of nanosized contrast agent with high radiodensity and specific biodistribution is an important parameter for localized tumor imaging and organ safety. Various nanoparticles, especially gold nanorods (GNRs), have been applied for tumor diagnosis. However, their toxicity, nonspecific biodistribution, and easy aggregation are critical issues in cancer medicine. To avoid these issues, encapsulation of the GNRs in the core of nanoscopic mesoporous silica (MS) under ambient conditions, yielding multifunctional nanomaterials for cancer nanomedicine, is a recent and active development. Interestingly, GNR embedded MS nanohybrid (GNR-MS), though a promising material in nanomedicine, is rarely examined for tumor diagnosis, in vivo toxicity, organ safety, contrast ability, and excretion. Herein, we report a systematic in vivo examination of folic acid functionalized GNR-MS (GNR-MS-FA) for localized 4T1 breast tumor diagnosis, organ safety, and excretion using a one-time dose administration. The nanomaterials show good aqueous dispersibility, biocompatibility, high radiodensity, and tumor specific targeting ability ( in vitro as well as in vivo). The in vivo tumor diagnosis and specific biodistribution of injected nanomaterials clearly demonstrates their potential for the visualization of tumors deep in the body of mice. In addition, all organs including the healthy glomerulus of the kidney are observed to be free of tissue injuries thereby indicating the superior biocompatibility of the nanomaterials.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste/química , Ácido Fólico/química , Ouro/química , Nanoestruturas/química , Dióxido de Silício/química , Animais , Materiais Biocompatíveis , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Meios de Contraste/administração & dosagem , Feminino , Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/metabolismo , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Distribuição Tecidual , Tomografia Computadorizada por Raios XRESUMO
The unresolved and paramount challenge in bio-imaging and targeted therapy is to clearly define and demarcate the physical margins of tumor tissue. The ability to outline the healthy vital tissues to be carefully navigated with transection while an intraoperative surgery procedure is performed sets up a necessary and under-researched goal. To achieve the aforementioned objectives, there is a need to optimize design considerations in order to not only obtain an effective imaging agent but to also achieve attributes like favorable water solubility, biocompatibility, high molecular brightness, and a tissue specific targeting approach. The emergence of near infra-red fluorescence (NIRF) light for tissue scale imaging owes to the provision of highly specific images of the target organ. The special characteristics of near infra-red window such as minimal auto-fluorescence, low light scattering, and absorption of biomolecules in tissue converge to form an attractive modality for cancer imaging. Imparting molecular fluorescence as an exogenous contrast agent is the most beneficial attribute of NIRF light as a clinical imaging technology. Additionally, many such agents also display therapeutic potentials as photo-thermal agents, thus meeting the dual purpose of imaging and therapy. Here, we primarily discuss molecular imaging and therapeutic potentials of two such classes of materials, i.e., inorganic NIR dyes and metallic gold nanoparticle based materials.
Assuntos
Nanoestruturas/química , Neoplasias/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho , Portadores de Fármacos/química , Corantes Fluorescentes/química , Corantes Fluorescentes/uso terapêutico , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Fotoquimioterapia , FototerapiaRESUMO
The post-pandemic era following the global spread of the SARS-CoV-2 virus has brought about persistent concerns regarding recurring coinfections. While significant strides in genome mapping, diagnostics, and vaccine development have controlled the pandemic and reduced fatalities, ongoing virus mutations necessitate a deeper exploration of the interplay between SARS-CoV-2 mutations and the host's immune response. Various vaccines, including RNA-based ones like Pfizer and Moderna, viral vector vaccines like Johnson & Johnson and AstraZeneca, and protein subunit vaccines like Novavax, have played critical roles in mitigating the impact of COVID-19. Understanding their strengths and limitations is crucial for tailoring future vaccines to specific variants and individual needs. The intricate relationship between SARS-CoV-2 mutations and the immune response remains a focus of intense research, providing insights into personalized treatment strategies and long-term effects like long-COVID. This article offers an overview of the post-pandemic landscape, highlighting emerging variants, summarizing vaccine platforms, and delving into immunological responses and the phenomenon of long-COVID. By presenting clinical findings, it aims to contribute to the ongoing understanding of COVID-19's progression in the aftermath of the pandemic.
Assuntos
COVID-19 , Coinfecção , Humanos , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Pandemias , Vacinas de Subunidades ProteicasRESUMO
Rheumatoid arthritis (RA) is one of the most prevalent life-long autoimmune diseases with an unknown genesis. It primarily causes chronic inflammation, pain, and synovial joint-associated cartilage and bone degradation. Unfortunately, limited information is available regarding the etiology and pathogenesis of this chronic joint disorder. In the last few decades, an improved understanding of RA pathophysiology about key immune cells, antibodies, and cytokines has inspired the development of several anti-rheumatic drugs and biopharmaceuticals to act on RA-affected joints. However, life-long frequent systemic high doses of commercially available drugs are currently a limiting factor in the efficient management of RA. To address this issue, various single and double-barrier intra-articular drug delivery systems (IA-DDSs) such as nanocarriers, microparticles, hydrogels, and particles-hybrid hydrogel composite have been developed which can exclusively target the RA-affected joint cavity and release the precisely controlled therapeutic drug concentration for prolonged time whilst avoiding the systemic toxicity. This review provides a comprehensive overview of the pathogenesis of RA and discusses the rational design and development of biomaterials-based novel IA-DDs, ranging from conventional to advanced systems, for improved treatment of RA. Therefore, this review aims to unravel the pathophysiology of rheumatoid arthritis and explore cutting-edge IA-DD strategies exploiting biomaterials. It offers researchers a consolidated and up-to-date resource platform to analyze existing knowledge, identify research gaps, and contribute to the scientific literature.
Assuntos
Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Articulações/metabolismo , Articulações/patologia , Sistemas de Liberação de Medicamentos , Inflamação/patologia , Materiais Biocompatíveis/uso terapêuticoRESUMO
Novel strategies modulating the immune system yielded enhanced anticancer responses and improved cancer survival. Nevertheless, the success rate of immunotherapy in cancer treatment has been below expectation(s) due to unpredictable efficacy and off-target effects from systemic dosing of immunotherapeutic(s). As a result, there is an unmet clinical need for improving conventional immunotherapy. Nanotechnology offers several new strategies, multimodality, and multiplex biological targeting advantage to overcome many of these challenges. These efforts enable programming the pharmacodynamics, pharmacokinetics, and delivery of immunomodulatory agents/co-delivery of compounds to prime at the tumor sites for improved therapeutic benefits. This review provides an overview of the design and clinical principles of biomaterials driven nanotechnology and their potential use in personalized nanomedicines, vaccines, localized tumor modulation, and delivery strategies for cancer immunotherapy. In this review, we also summarize the latest highlights and recent advances in combinatorial therapies availed in the treatment of cold and complicated tumors. It also presents key steps and parameters implemented for clinical success. Finally, we analyse, discuss, and provide clinical perspectives on the integrated opportunities of nanotechnology and immunology to achieve synergistic and durable responses in cancer treatment.
Assuntos
Imunoterapia/métodos , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Animais , Vacinas Anticâncer/administração & dosagem , Modelos Animais de Doenças , Portadores de Fármacos/química , Humanos , Fatores Imunológicos/administração & dosagem , Neoplasias/genética , Neoplasias/imunologiaRESUMO
Polymeric hydrogels and microparticles have been widely used for localized drug delivery applications for the treatment of arthritis. Nonetheless, owing to initial burst drug release, non-specific biodistribution and low retention time at the target site in body, these polymeric drug delivery systems have been found with low in-vivo performance. Hence, the above limitations need to be resolved by designing a smart novel drug delivery system which is the current need in biomedicine. Herein, a novel localized injectable thermoresponsive microparticles embedded hydrogel composite drug delivery system has been developed for the treatment of inflammatory arthritis. In the current study, methotrexate (MTX) loaded alginate microparticles (MTX-Microparticles) are embedded into thermoreversible hydrogel matrix (MTX-MPs-H) prepared by physical blending of sodium hyaluronate and methylcellulose (SHMC). Microparticles-hydrogel composite system exhibited appropriate in-vitro thermoreversibility (sol at 4 °C and gel at 37 °C), biocompatibility (>80 %), hemocompatibility, and controlled drug release profile. The in-vivo biocompatibility studies for 10 days revealed that composite system is non-toxic in nature. The developed MTX-MPs-H composite drug delivery system effectively decreased the swelling/ inflammation of the arthritis affected paw in wistar rats in comparison to only alginate microparticles and pure MTX up to 30 days.
Assuntos
Artrite , Hidrogéis , Alginatos , Animais , Artrite/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Ratos , Distribuição TecidualRESUMO
Developing a nanotheranostic agent with better image resolution and high accumulation into solid tumor microenvironment is a challenging task. Herein, we established a light mediated phototriggered strategy for enhanced tumor accumulation of nanohybrids. A multifunctional liposome based nanotheranostics loaded with gold nanoparticles (AuNPs) and emissive graphene quantum dots (GQDs) were engineered named as NFGL. Further, doxorubicin hydrochloride was encapsulated in NFGL to exhibit phototriggered chemotherapy and functionalized with folic acid targeting ligands. Encapsulated agents showed imaging bimodality for in vivo tumor diagnosis due to their high contrast and emissive nature. Targeted NFGL nanohybrids demonstrated near infrared light (NIR, 750 nm) mediated tumor reduction because of generated heat and Reactive Oxygen Species (ROS). Moreover, NFGL nanohybrids exhibited remarkable ROS scavenging ability as compared to GQDs loaded liposomes validated by antitumor study. Hence, this approach and engineered system could open new direction for targeted imaging and cancer therapy.
Assuntos
Doxorrubicina/administração & dosagem , Ouro/administração & dosagem , Grafite/administração & dosagem , Lipossomos/administração & dosagem , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Células 3T3 , Animais , Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama , Linhagem Celular Tumoral , Humanos , Raios Infravermelhos , Nanopartículas Metálicas/administração & dosagem , Camundongos , Pontos Quânticos/administração & dosagemRESUMO
Selective tissue visualization and localized tumor regression without affecting the surrounding healthy tissues are critical concerns in cancer nanomedicine. Importantly, the complete wrapping of a flimsy matrix like liposome by multifunctional graphene oxide is an interesting engineering idea for nanomedicine design. Moreover, designing a safe and biodegradable nanohybrid with significant theranostic ability is a current need for targeted combined therapies. Here, we report a comprehensive result of in vivo tumor diagnosis and phototriggered tumor regression using a biodegradable red emissive nanotheranostic system, viz., graphene oxide flakes fortified liposome (GOF-Lipo), functionalized with folic acid (FA): GOF-Lipo-FA. Graphene oxide support enhances the stability of drug-loaded liposomes in an extracellular environment that prevents the premature release of loaded anticancer drug from the liposomal cavity. Promising outcomes of tumor regression (â¼300 to 25 mm3) from organized cellular and animal studies are demonstrated in this work. These studies reveal superior biocompatibility, deep intracellular localization, 4T1 breast tumor diagnosis, and long time tumor binding ability of an injected emissive nanohybrid. Overall, a single dose of designed multifunctional systems demonstrates the best tumor regression.
RESUMO
We demonstrate facile and green synthesis of gold deposited zein nanoshells (AuZNS) using environmental benign solvent ethanol. Water soluble glycol chitosan is used for stabilization as well as for cationic functionalization of zein nanoparticles. Gold deposition is performed via ex-situ method at ambient conditions. AuZNS is of size around 100â¯nm and shows high inertness and biocompatibility even at double the therapeutic dosage. The absorbance is tuned at 808â¯nm for imaging-guided plasmonic photothermal therapy of cancer. Highly effective killing of cancer cells irrespective of their chemorefractory status is noticed at a very low therapeutic dosage of 25⯵g and 5â¯min of biologically acceptable (500â¯mW) 808â¯nm laser irradiation. AuZNS also exhibit better X-ray attenuation in comparison to the commercially available iodine based contrast agent.
Assuntos
Ouro/química , Nanopartículas Metálicas/química , Nanoconchas/química , Zeína/química , Animais , Linhagem Celular Tumoral , Humanos , Hipertermia Induzida , FototerapiaRESUMO
Herein we report synthesis, characterization and preclinical applications of a novel hybrid nanomaterial Toco-Photoxil developed using vitamin E modified gold coated poly (lactic-co-glycolic acid) nanoshells incorporating Pgp inhibitor d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a highly inert and disintegrable photothermal therapy (PTT) agent. Toco-Photoxil is highly biocompatible, physiologically stable PTT material with an average diameter of 130 nm that shows good passive accumulation (2.3% ID) in solid tumors when delivered systemically. In comparison to its surface modified counterparts such as IR780-Toco-Photoxil, FA-Toco-Photoxil or FA-IR780-Toco-Photoxil accumulation are merely ~0.3% ID, ~0.025% ID and ~0.005% ID in folate receptor (FR) negative and positive tumor model. Further, Toco-Photoxil variants are prepared by tuning the material absorbance either at 750 nm (narrow) or 915 nm (broad) to study optimal therapeutic efficacy in terms of peak broadness and nanomaterial's concentration. Our findings suggest that Toco-Photoxil tuned at 750 nm absorbance is more efficient (P = 0.0097) in preclinical setting. Toco-Photoxil shows complete passiveness in critical biocompatibility test and reasonable body clearance. High tumor specific accumulation from systemic circulation, strong photothermal conversion and a very safe material property in body physiology makes Toco-Photoxil a superior and powerful PTT agent, which may pave its way for fast track clinical trial in future.
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Fototerapia/métodos , Vitamina E/química , Animais , Feminino , Ácido Fólico/química , Hemólise , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Nanopartículas/química , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polímeros/química , Espectrofotometria InfravermelhoRESUMO
Specific targeting and phototriggered therapy in mouse model have recently emerged as the starting point of cancer theragnosis. Herein, we report a bioresponsive and degradable nanohybrid, a liposomal nanohybrid decorated with red emissive carbon dots, for localized tumor imaging and light-mediated tumor growth inhibition. Unsaturated carbon dots (C-dots) anchored to liposomes convert near-infrared (NIR) light into heat and also produce reactive oxygen species (ROS), demonstrating the capability of phototriggered cancer cell death and tumor regression. The photothermal and oxidative damage of breast tumor by the nonmetallic nanohybrid has also been demonstrated. Designed nanoparticles show excellent aqueous dispersibility, biocompatibility, light irradiated enhanced cellular uptake, release of reactive oxygen species, prolonged and specific tumor binding ability and good photothermal response (62 °C in 5 minutes). Safe and localized irradiation of 808 nm light demonstrates significant tumor growth inhibition and bioresponsive degradation of the fluorescent nanohybrid without affecting the surrounding healthy tissues.
Assuntos
Raios Infravermelhos , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/terapia , Fototerapia/métodos , Pontos Quânticos , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Lipossomos , Camundongos , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismoRESUMO
Integrating metallic and non-metallic platform for cancer nanomedicine is a challenging task and bringing together multi-functionality of two interfaces is a major hurdle for biomaterial design. Herein, NIR light responsive advanced hybrid plasmonic carbon nanomaterials are synthesized, and their properties toward repetitive and highly localized photothermal cancer therapy are well understood. Graphene oxide nanosheets having thickness of â¼2â¯nm are synthesized using modified Hummers' method, thereafter functionalized with biodegradable NIR light responsive gold deposited plasmonic polylactic-co-glycolic acid nanoshells (AuPLGA NS, tuned at 808 nm) and NIR dye (IR780) to examine their repetitive and localized therapeutic efficacy as well resulting side effects to nearby healthy cells. It is observed that AuPLGA NS decorated graphene oxide nanosheets (GO-AuPLGA) and IR780 loaded graphene oxide nanosheets (GO-IR780) are capable in standalone complete photothermal ablation of cancer cells within 4 min. of 808 nm NIR laser irradiation and also without the aid of any anticancer drugs. However, GO-AuPLGA having the potential for repetitive photothermal treatment of a big tumor, ablate the cancer cells in highly localized fashion, without having side effects on neighboring healthy cells.
Assuntos
Carbono/química , Hipertermia Induzida , Nanoestruturas/química , Neoplasias/terapia , Fototerapia , Linhagem Celular Tumoral , Grafite/química , Humanos , Indóis/química , Nanoestruturas/ultraestrutura , Neoplasias/patologia , Espectroscopia Fotoeletrônica , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral RamanRESUMO
Cotton fibres coated with biogenically fabricated silver nanoparticles (SNPs) are most sought material because of their enhanced activity and biocompatibility. After successful synthesis of SNPs on cotton fibres using leaf extract of Vitex negundo Linn, the fibres were studied using diffuse reflectance spectroscopy, scanning electron microscopy, nanoparticle tracking analysis, energy dispersive X-ray, and inductively coupled plasma atomic emission spectrometry. The characterisation revealed uniformly distributed spherical agglomerates of SNPs having individual particle size around 50â nm with the deposition load of 423â µg of silver per gram of cotton. Antimicrobial assay of cotton-SNPs fibres showed effective performance against pathogenic bacteria and fungi. The method is biogenic, environmentally benign, rapid, and cost-effective, producing highly biocompatible antimicrobial coating required for the healthcare industry.
Assuntos
Materiais Biocompatíveis , Fibra de Algodão , Atenção à Saúde/organização & administração , Nanopartículas Metálicas/química , Prata/química , Microscopia Eletrônica de Varredura , Espectrometria por Raios X , Espectrofotometria AtômicaRESUMO
Designing bioresponsive nanocarriers for controlled and efficient intracellular drug release for cancer therapy is a major thrust area in nanomedicine. With recent recognition by the US FDA as a safe material for human trials, mesoporous silica nanoparticles (MSNPs) are being extensively explored as promising theranostic agents. Green fluorescent carbon quantum dots (CQDs), though known as possible alternatives for their more toxic and relatively less efficient predecessors, are less known as gate keepers for drug release control. We report for the first time an efficient bioresponse of CQDs when judiciously designed using glutathione cleavable (redox responsive) disulphide bonds. When the anticancer drug doxorubicin loaded MSNPs are capped with these CQDs, they display promising drug release control on exposure to a mimicked intracellular cancer environment. Their dual functionality is well established with good control on preventing the premature release and exceptional bio-imaging of HeLa cancer cells. Fluorescence images prove selective targeting of HeLa cells by overexpression of folate receptors from the surface functionalised folic acid ligand. Extensive characterisation using XRD, TEM, BET analysis, drug loading tests, drug release kinetics, MTT assay and fluoroscence cell imaging helps in understanding the multifunctionalities of the successful design, extending its scope with exciting prospects towards non-invasive targeted drug delivery and bio-imaging for effective cancer diagnosis and treatment.