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1.
Langmuir ; 37(14): 4137-4146, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33813823

RESUMO

Hydroxyapatite (HA) is the main inorganic component of human bones and teeth. It has good biocompatibility and bioactivity, which promotes its good application prospects in the field of bone drug carriers. In this study, tetraethylenepentamine-graphene (rGO-TEPA)/CaCO3:HA composite microspheres were prepared via microwave hydrothermal synthesis using rGO-TEPA/CaCO3 solid microspheres as intermediates. Furthermore, the incompletely transformed CaCO3 was removed by soaking in a citric acid buffer to obtain rGO-TEPA/HA hollow composite microspheres. The two types of as-prepared composite microspheres exhibited sea urchin-like structures, large BET surface areas, and good dispersibility. Mouse preosteoblast cells (MC3T3-E1) were used for in vitro cytotoxicity experiments. The in vitro cell viability test showed that the two composite drug carriers exhibited noncytotoxicity. Moreover, the doxorubicin (DOX) loading and releasing investigations revealed that the two types of prepared carriers had mild storage-release behaviors and good pH responsiveness. Hence, these rGO-TEPA/HA hollow microspheres have promising applications as bone drug carriers.


Assuntos
Materiais Biomiméticos , Osso e Ossos/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Durapatita , Grafite , Microesferas , Ouriços-do-Mar , Animais , Osso e Ossos/citologia , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/farmacologia , Etilenodiaminas , Concentração de Íons de Hidrogênio , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos
2.
Molecules ; 26(2)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33419179

RESUMO

A new conjugate of gallato zirconium (IV) phthalocyanine complexes (PcZrGallate) has been obtained from alkilamino-modified SiO2 nanocarriers (SiO2-(CH2)3-NH2NPs), which may potentially be used in photodynamic therapy of atherosclerosis. Its structure and morphology have been investigated. The photochemical properties of the composite material has been characterized. in saline environments when exposed to different light sources Reactive oxygen species (ROS) generation in DMSO suspension under near IR irradiation was evaluated. The PcZrGallate-SiO2 conjugate has been found to induce a cytotoxic effect on macrophages after IR irradiation, which did not correspond to ROS production. It was found that SiO2 as a carrier helps the photosensitizer to enter into the macrophages, a type of cells that play a key role in the development of atheroma. These properties of the novel conjugate may make it useful in the photodynamic therapy of coronary artery disease.


Assuntos
Complexos de Coordenação , Portadores de Fármacos , Indóis , Fotoquimioterapia , Fármacos Fotossensibilizantes , Placa Aterosclerótica , Dióxido de Silício , Zircônio , Animais , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Indóis/química , Indóis/farmacologia , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Células RAW 264.7 , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Zircônio/química , Zircônio/farmacologia
3.
Carbohydr Polym ; 255: 117393, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33436222

RESUMO

In this paper, a novel redox-responsive nanoparticles has been designed for targeted delivery of docetaxel (DTX). Chondroitin sulfate (CS) was used to construct the nanoparticles due to the ability of tumor targeting through binding with CD44 receptor that overexpresses on the surfaces of various tumor cells. A redox-responsive small-molecular DTX prodrug was prepared through modifying with cystamine containing disulfide bonds (Cys-DTX). Then the DTX prodrug was grafted to the CS to construct the amphiphilic polymer (CS-ss-DTX). Further, Cys-DTX/CS-ss-DTX nanoparticles were formed by self-assembly of amphiphilic polymer and incorporation of free Cys-DTX prodrug. This category of nanosized DTX delivery system was expected for not only exhibiting high permeability and cytotoxicity of Cys-DTX prodrug, but also targeting transportation of encapsulated redox-responsive Cys-DTX prodrug. According to results of related researches on physicochemical properties and biological evaluation, the novel redox-responsive Cys-DTX/CS-ss-DTX nanoparticles increased amount of DTX released from the nanoparticles in reductive environment, improved permeability in tumor tissues, enhanced cytotoxicity and decreased side effects compared with free DTX. All of these results showed that this kind of Cys-DTX/CS-ss-DTX nanoparticles were worthy of being expectation in tumor chemotherapy in future.


Assuntos
Antineoplásicos/farmacologia , Sulfatos de Condroitina/química , Docetaxel/farmacologia , Glicoconjugados/farmacologia , Melanoma Experimental/tratamento farmacológico , Pró-Fármacos/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Docetaxel/química , Docetaxel/metabolismo , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Feminino , Glicoconjugados/química , Glicoconjugados/metabolismo , Humanos , Células MCF-7 , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Micelas , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/ultraestrutura , Oxirredução , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Carga Tumoral/efeitos dos fármacos
4.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430158

RESUMO

(1) Background: Chiral nanoparticular systems have recently emerged as a compelling platform for investigating stereospecific behavior at the nanoscopic level. We describe chiroselective supramolecular interactions that occur between DNA oligonucleotides and chiral polyurea nanocapsules. (2) Methods: We employ interfacial polyaddition reactions between toluene 2,4-diisocyanate and lysine enantiomers that occur in volatile oil-in-water nanoemulsions to synthesize hollow, solvent-free capsules with average sizes of approximately 300 nm and neutral surface potential. (3) Results: The resultant nanocapsules exhibit chiroptical activity and interact differentially with single stranded DNA oligonucleotides despite the lack of surface charge and, thus, the absence of significant electrostatic interactions. Preferential binding of DNA on D-polyurea nanocapsules compared to their L-counterparts is demonstrated by a fourfold increase in capsule size, a 50% higher rise in the absolute value of negative zeta potential (ζ-potential), and a three times lower free DNA concentration after equilibration with the excess of DNA. (4) Conclusions: We infer that the chirality of the novel polymeric nanocapsules affects their supramolecular interactions with DNA, possibly through modification of the surface morphology. These interactions can be exploited when developing carriers for gene therapy and theranostics. The resultant constructs are expected to be highly biocompatible due to their neutral potential and biodegradability of polyurea shells.


Assuntos
DNA/química , Portadores de Fármacos/farmacologia , Nanocápsulas/química , Oligonucleotídeos/química , Aptâmeros de Nucleotídeos/química , DNA/antagonistas & inibidores , Portadores de Fármacos/química , Emulsões/química , Emulsões/farmacologia , Humanos , Oligonucleotídeos/genética , Tamanho da Partícula , Polímeros/química
5.
Nat Commun ; 12(1): 440, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469052

RESUMO

The main challenges for programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) checkpoint blockade lie in a lack of sufficient T cell infiltration, tumor immunosuppressive microenvironment, and the inadequate tumor accumulation and penetration of anti-PD-1/PD-L1 antibody. Resetting tumor-associated macrophages (TAMs) is a promising strategy to enhance T-cell antitumor immunity and ameliorate tumor immunosuppression. Here, mannose-modified macrophage-derived microparticles (Man-MPs) loading metformin (Met@Man-MPs) are developed to efficiently target to M2-like TAMs to repolarize into M1-like phenotype. Met@Man-MPs-reset TAMs remodel the tumor immune microenvironment by increasing the recruitment of CD8+ T cells into tumor tissues and decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells. More importantly, the collagen-degrading capacity of Man-MPs contributes to the infiltration of CD8+ T cells into tumor interiors and enhances tumor accumulation and penetration of anti-PD-1 antibody. These unique features of Met@Man-MPs contribute to boost anti-PD-1 antibody therapy, improving anticancer efficacy and long-term memory immunity after combination treatment. Our results support Met@Man-MPs as a potential drug to improve tumor resistance to anti-PD-1 therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Micropartículas Derivadas de Células/imunologia , Portadores de Fármacos/farmacologia , Neoplasias/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Humanos , /uso terapêutico , Memória Imunológica , Masculino , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Células RAW 264.7 , Evasão Tumoral/efeitos dos fármacos , Evasão Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , /imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Methods Mol Biol ; 2207: 327-338, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113145

RESUMO

Cancer constitutes a major threat to humanity, while its incidence and mortality rates are increasing rapidly worldwide. To tackle cancer, numerous strategies have been exploited, including the development of peptide-drug conjugates (PDCs), which are considered an appealing approach to selectively populate malignant tumors with toxic substances. The general architecture of a PDC usually includes three parts: the tumor-targeting peptide, the cytotoxic drug, and the biodegradable linker. Due to the fact that peptides possess fast renal clearance, affecting the bioavailability of the PDC, a nanodrug formation concept can be exploited to ameliorate this pitfall. Herein, we present methodologies to develop PDCs, along with certain basic principles governing such constructs. In addition, we highlight possible problems that may appear during the synthesis of PDCs, as also solutions to overcome them.


Assuntos
Antineoplásicos , Portadores de Fármacos , Nanoestruturas , Neoplasias , Peptídeos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Peptídeos/química , Peptídeos/farmacocinética , Peptídeos/farmacologia
7.
Methods Mol Biol ; 2207: 85-97, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113129

RESUMO

This chapter focuses on the in vitro biological evaluation of multisensitive nanocontainers as drug delivery systems for cancer treatment. Cancer tissues possess some unique characteristics such as increased temperature due to inflammation, thermal vulnerability (40-45 °C), low cellular pH, and redox instabilities. The employment of polymers bearing pH, thermo, and/or redox sensitivities in the synthesis of hollow polymeric nanostructures has led to the formulation of a variety of drug delivery vehicles that are capable of targeted delivery and trigger specific drug release. The cavity in the structure allows for the encapsulation of anticancer drugs as well as other moieties with anticancer activity, like iron oxide magnetic nanoparticles. The drug loading and release capability of the nanocontainers is evaluated prior to biological studies in order to determine the concentration of the drug in the structure. The in vitro assessment includes cytotoxicity studies, quantitatively through the colorimetric MTT assay as well as qualitatively via the scratch-wound healing assay, on both cancer and healthy cell lines. The cellular localization of the studied drug-loaded and unloaded nanocontainers is determined through confocal fluorescence microscopy.


Assuntos
Antineoplásicos , Portadores de Fármacos , Nanopartículas de Magnetita , Neoplasias , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
8.
Methods Mol Biol ; 2207: 127-137, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113132

RESUMO

Over the last two decades, remarkable progress has been made to the discovery of novel drugs as well as their delivery systems for the treatment of cancer, the major challenge in medicine. Pharmaceutical scientists are trying to shift from traditional to novel drug delivery systems by applying nanotechnology and, in particular, polymeric carriers to medicine. In complex diseases, very sophisticated nanocarriers should be designed to encapsulate a significant quantity of drugs and bypass biological barriers with minimum cargo loss to effectively and directly deliver the encapsulated drug to the desired pathological site. One of the most promising classes of polymeric materials for drug delivery applications is polypeptides, combining the properties of the traditional polymers with the 3D structure of natural proteins, i.e., a-helices and ß-sheets. In this chapter, we present the recent progress in the synthesis of polymers that form hydrogels in aqueous solutions, based on polypeptides prepared through ring-opening polymerization of N-carboxy anhydrides and which have been loaded with anticancer drugs and studied for their functionality. Advancements in drug design and improvement of multifunctional nanocarriers from the combination of well-defined macromolecular architectures and smart materials are the future for the successful treatment of numerous lethal diseases.


Assuntos
Antineoplásicos , Portadores de Fármacos , Desenho de Fármacos , Hidrogéis , Neoplasias , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacocinética , Hidrogéis/farmacologia , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
9.
Methods Mol Biol ; 2207: 139-150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113133

RESUMO

Recently, the explosion of progress of materials at the nanoscale level has paved the way for a new category of healthcare technologies termed nanomedicine. Nanomedicine involves materials at the nanometer level for products that can improve the currently used technologies for biomedical applications. While traditional therapeutics have allowed for limited control of their distribution in the body and clearing times, engineering at the nanoscale level has allowed for significant advances in biocompatibility, biodistribution, and pharmacokinetics. Among all materials, polymers have dominated the nanomedicine world, due to their ability to manipulate their properties by combining different materials in a wide variety of macromolecular architectures. The development of novel polymeric materials is guided by the goal of improving patient survival and quality of life by increasing the bioavailability of drug to the site of disease, targeting delivery to the pathological tissues, increasing drug solubility, and minimizing systemic side effects. Polymersomes (vesicles) are the only type of polymeric nanocarriers that can physically encapsulate at the same nanoparticle hydrophilic drugs in their aqueous interior and/or hydrophobic agents within their lamellar membranes. Polymersomes have been shown to possess superior biomaterial properties compared to liposomes, including greater stability and storage capabilities, as well as prolonged circulation time.


Assuntos
Antineoplásicos , Portadores de Fármacos , Nanopartículas , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Peptídeos/química , Peptídeos/farmacocinética , Peptídeos/farmacologia
10.
Methods Mol Biol ; 2207: 151-161, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113134

RESUMO

Common chemotherapeutic drugs exhibit no specificity for cancer cells and destroy simultaneously healthy cells exhibiting high toxicity and reduced efficacy. The use of nanotechnology, especially of drug delivery systems to the size of the nanoscale, provides rational drug design solutions. Such nanomaterials may have a range of desired characteristics (lack of toxicity, response to certain characteristics of the cancer cells, antimicrobial properties, specific activity, etc.) in order to achieve targeted cancer therapy. In this chapter, polymeric systems with core-shell structure are synthesized, characterized, and studied as potent drug delivery devices for targeted cancer therapy. These polymeric systems are based on natural polysaccharides like cellulose, chitosan, and their derivatives, in combination with synthetic polymer. Polymethylmethacrylate (PMMA) nanospheres are used as a core in order to coat the surface with multiple layers of polysaccharides via layer-by-layer deposition. This design is advantageous due to the use of water as the appropriate solvent. Fabricated polymeric carriers are characterized structurally by AT-IR spectroscopy and morphologically by transmission (TEM) and scanning electron microscopy (SEM). Finally, daunorubicin, an anticancer agent, was encapsulated as a drug model into the carriers.


Assuntos
Antineoplásicos , Celulose/química , Quitosana/química , Portadores de Fármacos , Nanosferas , Neoplasias/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Nanosferas/química , Nanosferas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Polimetil Metacrilato/química
11.
Methods Mol Biol ; 2207: 175-186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113136

RESUMO

Cancer occupies a high rank in the global morbidity and mortality scale with glioblastoma multiforme (GBM) accounting for almost 80% of all primary tumors of the brain. Despite the increasing availability of targeted and immunotherapeutic agents, chemotherapy still plays an important role in the treatment of neoplastic diseases. Limitations to the effective use of chemotherapy such as low aqueous solubility and high toxicity have directed the scientific community's interest to the development of new therapeutic agents with enhanced efficacy and limited toxicity. Supramolecular chemistry has offered an alternative way on the design and development of new therapeutic agents as a result of their unique properties. Supramolecules can be used as drug carriers since their cavities can host a wide range of small drugs and surpass in this way the drawbacks of current therapeutic agents. Herein, we present the principles that should be followed for the encapsulation of small drugs in supramolecules with enhanced physicochemical properties and increased efficacy against glioblastoma multiforme.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Portadores de Fármacos , Glioblastoma , Temozolomida , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Camundongos , Solubilidade , Temozolomida/química , Temozolomida/farmacocinética , Temozolomida/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Methods Mol Biol ; 2207: 199-220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113138

RESUMO

Ceranib-2 is a recently discovered, poorly water-soluble potent ceramidase inhibitor, with the ability to suppress cancer cell proliferation and delay tumor growth. However, its poor water solubility and weak cellular bioavailability hinder its use as a therapeutic agent for cancer. PEGylated rosin esters are an excellent platform as a natural polymer for drug delivery applications, especially for controlling drug release due to their degradability, biocompatibility, capability to improve solubility, and pharmacokinetics of potent drugs. In this study, stable aqueous amphiphilic submicron-sized PEG400-rosin ester-ceranib-2 (PREC-2) particles, ranging between 100 and 350 nm in a 1:1 mixture, were successfully synthesized by solvent evaporation mediated by sonication.Conclusion: Stable aqueous PEGylated rosin ester nanocarriers might present a significant solution to improve solubility, pharmacokinetic, and bioavailability of ceranib-2, and hold promises for use as an anticancer adjacent drug after further investigations.


Assuntos
Antineoplásicos , Portadores de Fármacos , Neoplasias , Polietilenoglicóis/química , Quinolonas , Resinas Vegetais/química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Células HeLa , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Quinolonas/química , Quinolonas/farmacocinética , Quinolonas/farmacologia
13.
Carbohydr Polym ; 253: 117258, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278940

RESUMO

Use of polysaccharides as carriers in drug delivery system is a hot topic, especially those with specific recognition of immune cells, enabling them to be applied in targeting delivery system. ß-d-glucans are naturally occurring non-digestible polysaccharides with immunomodulatory activities that have attracted increasing attention to serve as therapeutic agents or immune-adjuvants. Being able to be specifically recognized by immune cells like macrophages, ß-d-glucans can be developed as promising carriers for targeting delivery with stability, biocompatibility and specificity when applied in immunotherapy. Targeting tumor associated macrophages (TAMs) is an emerging strategy for cancer immunotherapy since it exerts anti-cancer effects based on modulating body immunity in tumor microenvironment (TME). This new strategy does not require high concentration of drugs to kill cancer cells directly and lessen tumor recurrence by creating unique immune memory for malignant cells. In this review, construction strategies of polysaccharide-based drug delivery system of three types of ß-d-glucan including non-yeast and yeast ß-d-glucans as well as hyper-branched ß-d-glucan are discussed with reference to their branching characteristics and conformation. The applications of these ß-d-glucans as nano-carrier for drug delivery targeting TAMs are also discussed.


Assuntos
Portadores de Fármacos/farmacologia , Fatores Imunológicos/farmacologia , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , beta-Glucanas/farmacologia , Animais , Humanos , Fatores Imunológicos/química , Conformação Molecular , Solubilidade , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Leveduras/metabolismo , beta-Glucanas/química
14.
Nat Commun ; 11(1): 5618, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154372

RESUMO

Systemic chemotherapy remains the backbone of many cancer treatments. Due to its untargeted nature and the severe side effects it can cause, numerous nanomedicine approaches have been developed to overcome these issues. However, targeted delivery of therapeutics remains challenging. Engineering microrobots is increasingly receiving attention in this regard. Their functionalities, particularly their motility, allow microrobots to penetrate tissues and reach cancers more efficiently. Here, we highlight how different microrobots, ranging from tailor-made motile bacteria and tiny bubble-propelled microengines to hybrid spermbots, can be engineered to integrate sophisticated features optimised for precision-targeting of a wide range of cancers. Towards this, we highlight the importance of integrating clinicians, the public and cancer patients early on in the development of these novel technologies.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Robótica , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Humanos , Comunicação Interdisciplinar , Nanomedicina , Robótica/classificação
15.
Int J Nanomedicine ; 15: 5181-5202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801685

RESUMO

Background: Combating infectious diseases caused by influenza virus is a major challenge due to its resistance to available drugs and vaccines, side effects, and cost of treatment. Nanomedicines are being developed to allow targeted delivery of drugs to attack specific cells or viruses. Materials and Methods: In this study, mesoporous silica nanoparticles (MSNs) functionalized with amino groups and loaded with natural prodrugs of shikimic acid (SH), quercetin (QR) or both were explored as a novel antiviral nanoformulations targeting the highly pathogenic avian influenza H5N1 virus. Also, the immunomodulatory effects were investigated in vitro tests and anti-inflammatory activity was determined in vivo using the acute carrageenan-induced paw edema rat model. Results: Prodrugs alone or the MSNs displayed weaker antiviral effects as evidenced by virus titers and plaque formation compared to nanoformulations. The MSNs-NH2-SH and MSNs-NH2-SH-QR2 nanoformulations displayed a strong virucidal by inactivating the H5N1 virus. They induced also strong immunomodulatory effects: they inhibited cytokines (TNF-α, IL-1ß) and nitric oxide production by approximately 50% for MSNs-NH2-SH-QR2 (containing both SH and QR). Remarkable anti-inflammatory effects were observed during in vivo tests in an acute carrageenan-induced rat model. Conclusion: Our preliminary findings show the potential of nanotechnology for the application of natural prodrug substances to produce a novel safe, effective, and affordable antiviral drug.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antivirais/farmacologia , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Nanopartículas/química , Pró-Fármacos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/imunologia , Antivirais/imunologia , Citocinas/metabolismo , Cães , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Edema/tratamento farmacológico , Edema/metabolismo , Fatores Imunológicos/imunologia , Fatores Imunológicos/farmacologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Quercetina/imunologia , Quercetina/farmacologia , Ratos , Ácido Chiquímico/imunologia , Ácido Chiquímico/farmacologia , Dióxido de Silício/química
16.
PLoS One ; 15(8): e0237218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760143

RESUMO

Influenza is an infectious respiratory illness caused by influenza viruses. Despite yearly updates, the efficacy of influenza vaccines is significantly curtailed by the virus antigenic drift and antigenic shift. These constant changes to the influenza virus make-up also challenge the development of a universal flu vaccine, which requires conserved antigenic regions shared by influenza viruses of different subtypes. We propose that it is possible to bypass these challenges by the development of an influenza vaccine based on conserved proteins delivered in an adjuvanted nanoparticle system. In this study, we generated influenza nanoparticle constructs using trimethyl chitosan nanoparticles (TMC nPs) as the carrier of recombinant influenza hemagglutinin subunit 2 (HA2) and nucleoprotein (NP). The purified HA2 and NP recombinant proteins were encapsulated into TMC nPs to form HA2-TMC nPs and NP-TMC nPs, respectively. Primary human intranasal epithelium cells (HNEpCs) were used as an in vitro model to measure immunity responses. HA2-TMC nPs, NP-TMC nPs, and HA2-NP-TMC nPs (influenza nanoparticle constructs) showed no toxicity in HNEpCs. The loading efficiency of HA2 and NP into the TMC nPs was 97.9% and 98.5%, respectively. HA2-TMC nPs and NP-TMC nPs more efficiently delivered HA2 and NP proteins to HNEpCs than soluble HA2 and NP proteins alone. The induction of various cytokines and chemokines was more evident in influenza nanoparticle construct-treated HNEpCs than in soluble protein-treated HNEpCs. In addition, soluble factors secreted by influenza nanoparticle construct-treated HNEpCs significantly induced MoDCs maturation markers (CD80, CD83, CD86 and HLA-DR), as compared to soluble factors secreted by protein-treated HNEpCs. HNEpCs treated with the influenza nanoparticle constructs significantly reduced influenza virus replication in an in vitro challenge assay. The results indicate that TMC nPs can be used as influenza vaccine adjuvants and carriers capable of delivering HA2 and NP proteins to HNEpCs.


Assuntos
Adjuvantes Imunológicos/farmacologia , Quitosana/farmacologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/farmacologia , Influenza Humana/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Animais , Linhagem Celular , Células Cultivadas , Quitosana/administração & dosagem , Cães , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/farmacologia , Humanos , Vacinas contra Influenza/administração & dosagem , Influenza Humana/imunologia , Células Madin Darby de Rim Canino , Nanopartículas/administração & dosagem , Proteínas do Nucleocapsídeo , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Proteínas de Ligação a RNA/administração & dosagem , Proteínas de Ligação a RNA/farmacologia , Proteínas do Core Viral/administração & dosagem , Proteínas do Core Viral/farmacologia
17.
Int J Pharm ; 588: 119689, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32717282

RESUMO

A handful of singular structures and laws can be observed in nature. They are not always evident but, once discovered, it seems obvious how to take advantage of them. In chemistry, the discovery of reproducible patterns stimulates the imagination to develop new functional materials and technological or medical applications. Two clear examples are helical structures at different levels in biological polymers as well as ring and spherical structures of different size and composition. Rings are intuitively observed as holes able to thread elongated structures. A large number of real and fictional stories have rings as inanimate protagonists. The design, development or just discovering of a special ring has often been taken as a symbol of power or success. Several examples are the Piscatory Ring wore by the Pope of the Catholic Church, the NBA Championship ring and the One Ring created by the Dark Lord Sauron in the epic story The Lord of the Rings. In this work, we reveal the power of another extremely powerful kind of rings to fight against the pandemic which is currently affecting the whole world. These rings are as small as ~1 nm of diameter and so versatile that they are able to participate in the attack of viruses, and specifically SARS-CoV-2, in a large range of different ways. This includes the encapsulation and transport of specific drugs, as adjuvants to stabilize proteins, vaccines or other molecules involved in the infection, as cholesterol trappers to destabilize the virus envelope, as carriers for RNA therapies, as direct antiviral drugs and even to rescue blood coagulation upon heparin treatment. "One ring to rule them all. One ring to find them. One ring to bring them all and in the darkness bind them." J. R. R. Tolkien.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Ciclodextrinas/química , Ciclodextrinas/farmacologia , Nanoestruturas , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Estabilidade de Medicamentos , Excipientes/química , Excipientes/farmacologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/química , Vacinas Virais/farmacologia
18.
Nat Biomed Eng ; 4(7): 717-731, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32632229

RESUMO

The rapid elimination of nanoparticles from the bloodstream by the mononuclear phagocyte system limits the activity of many nanoparticle formulations. Here, we show that inducing a slight and transient depletion of erythrocytes in mice (~5% decrease in haematocrit) by administrating a low dose (1.25 mg kg-1) of allogeneic anti-erythrocyte antibodies increases the circulation half-life of a range of short-circulating and long-circulating nanoparticle formulations by up to 32-fold. Treatment of the animals with anti-erythrocyte antibodies significantly improved the targeting of CD4+ cells in vivo with fluorescent anti-CD4-antibody-conjugated nanoparticles, the magnetically guided delivery of ferrofluid nanoparticles to subcutaneous tumour allografts and xenografts, and the treatment of subcutaneous tumour allografts with magnetically guided liposomes loaded with doxorubicin and magnetite or with clinically approved 'stealthy' doxorubicin liposomes. The transient and partial blocking of the mononuclear phagocyte system may enhance the performance of a wide variety of nanoparticle drugs.


Assuntos
Circulação Sanguínea/fisiologia , Portadores de Fármacos/farmacologia , Eritrócitos , Nanomedicina/métodos , Animais , Anticorpos , Linfócitos T CD4-Positivos , Citocinas/metabolismo , Doxorrubicina/análogos & derivados , Eritrócitos/imunologia , Feminino , Meia-Vida , Xenoenxertos , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Nanopartículas/administração & dosagem , Polietilenoglicóis , Ratos , Ratos Wistar , Sepse/tratamento farmacológico
20.
Ultrasonics ; 108: 106198, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32590261

RESUMO

Contrast-enhanced ultrasound (CEUS) is widely applied in cancer diagnosis clinically. However, the gas-filled contrast agents are unstable in the blood and exhibit shorter imaging time, which limit their clinical use. In this study, a diagnostic nanoparticle system was developed for dual-mode imaging (ultrasound and fluorescence), which after encapsulation with doxorubicin (DOX) demonstrated simultaneous therapeutic function towards cancer treatment. Thus, calcium carbonate (CaCO3) nanoparticles were encapsulated with doxorubicin (DOX) to obtain CaCO3-DOX. Under acidic conditions, it produced carbon dioxide (CO2) to enhance ultrasound imaging and increase the release of DOX. After intravenously injecting CaCO3-DOX to tumor-bearing mice, in the presence of an ultrasound field, CO2bubbles were sufficiently generated at the tumor tissues for echogenic reflectivity. Also, the indocyanine green (ICG) was encapsulated into CaCO3 nanoparticles, to further detect the tumor with fluorescence. The resultant theranostic nanoparticle system exhibited therapeutic efficacy towards tumour-bearing mice. Overall, this investigation provides an attractive strategy for dual-mode cancer diagnostics.


Assuntos
Carbonato de Cálcio/farmacologia , Doxorrubicina/farmacologia , Imagem Multimodal , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Ultrassonografia/métodos , Animais , Carbonato de Cálcio/química , Dióxido de Carbono/metabolismo , Linhagem Celular Tumoral , Meios de Contraste , Doxorrubicina/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Fluorescência , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Microambiente Tumoral
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