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1.
Beilstein J Nanotechnol ; 15: 1077-1104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39188756

RESUMO

Sensors are applied to many fields nowadays because of their high sensitivity, low cost, time-saving, user-friendly, and excellent selectivity. Current biomedical and pharmaceutical science has one focus on developing nanoparticle-based sensors, especially biopolymeric nanoparticles. Alginate is a widely used biopolymer in a variety of applications. The hydrogel-forming characteristic, the chemical structure with hydroxy and carboxylate moieties, biocompatibility, biodegradability, and water solubility of alginate have expanded opportunities in material and biomedical sciences. Recently, research on alginate-based nanoparticles and their applications has begun. These materials are gaining popularity because of their wide usage potential in the biomedical and pharmaceutical fields. Many review papers describe applications of alginate in the drug delivery field. The current study covers the structural and physicochemical properties of alginate-based nanoparticles. The prospective applications of alginate-based nanomaterials in various domains are discussed, including drug delivery and environmental sensing applications for humidity, heavy metals, and hydrogen peroxide. Moreover, biomedical sensing applications of alginate-based nanoparticles regarding various analytes such as glucose, cancer cells, pharmaceutical drugs, and human motion will also be reviewed in this paper. Future research scopes highlight existing challenges and solutions.

2.
Drug Deliv ; 31(1): 2372269, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38956885

RESUMO

Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.


Assuntos
Acne Vulgar , Portadores de Fármacos , Folículo Piloso , Polímeros , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Acne Vulgar/tratamento farmacológico , Humanos , Polímeros/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas , Administração Cutânea , Animais , Sistemas de Liberação de Fármacos por Nanopartículas/química
3.
Artigo em Inglês | MEDLINE | ID: mdl-38758497

RESUMO

Rheumatoid arthritis (RA) is a systemic immune disease with severe implications for joint health. The issue of non-specific drug distribution potentially limits the therapeutic efficacy and increases the risk associated with RA treatment. Researchers employed cytomembrane-coated biomimetic nanoparticles (NPs) to enhance the targeting delivery efficacy to meet the demand for drug accumulation within the affected joints. Furthermore, distinct cytomembranes offer unique functionalities, such as immune cell activation and augmented NP biocompatibility. In this review, the current strategies of RA treatments were summarized in detail, and then an overview of RA's pathogenesis and the methodologies for producing cytomembrane-coated biomimetic NPs was provided. The application of cytomembrane biomimetic NPs derived from various cell sources in RA therapy is explored, highlighting the distinctive attributes of individual cytomembranes as well as hybrid membrane configurations. Through this comprehensive assessment of cytomembrane biomimetic NPs, we elucidate the prospective applications and challenges in the realm of RA therapy, and the strategy of combined therapy is proposed. In the future, cytomembrane biomimetic NPs have a broad therapeutic prospect for RA.

4.
Adv Mater ; 36(30): e2404645, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38678386

RESUMO

In the realm of cancer therapy, the spotlight is on nanoscale pharmaceutical delivery systems, especially polymer-based nanoparticles, for their enhanced drug dissolution, extended presence in the bloodstream, and precision targeting achieved via surface engineering. Leveraging the amplified permeation and retention phenomenon, these systems concentrate therapeutic agents within tumor tissues. Nonetheless, the hurdles of systemic toxicity, biological barriers, and compatibility with living systems persist. Fluorinated polymers, distinguished by their chemical idiosyncrasies, are poised for extensive biomedical applications, notably in stabilizing drug metabolism, augmenting lipophilicity, and optimizing bioavailability. Material science heralds the advent of fluorinated polymers that, by integrating fluorine atoms, unveil a suite of drug delivery merits: the hydrophobic traits of fluorinated alkyl chains ward off lipid or protein disruption, the carbon-fluorine bond's stability extends the drug's lifecycle in the system, and a lower alkalinity coupled with a diminished ionic charge bolsters the drug's ability to traverse cellular membranes. This comprehensive review delves into the utilization of fluorinated polymers for oncological pharmacotherapy, elucidating their molecular architecture, synthetic pathways, and functional attributes, alongside an exploration of their empirical strengths and the quandaries they encounter in both experimental and clinical settings.


Assuntos
Antineoplásicos , Halogenação , Neoplasias , Polímeros , Humanos , Polímeros/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Interações Hidrofóbicas e Hidrofílicas
5.
ACS Biomater Sci Eng ; 10(5): 2911-2924, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38657240

RESUMO

Macrophage uptake of nanoparticles is highly dependent on the physicochemical characteristics of those nanoparticles. Here, we have created a collection of lipid-polymer nanoparticles (LPNPs) varying in size, stiffness, and lipid makeup to determine the effects of these factors on uptake in murine bone marrow-derived macrophages. The LPNPs varied in diameter from 232 to 812 nm, in storage modulus from 21.2 to 287 kPa, and in phosphatidylserine content from 0 to 20%. Stiff, large nanoparticles with a coating containing phosphatidylserine were taken up by macrophages to a much higher degree than any other formulation (between 9.3× and 166× higher than other LPNPs). LPNPs with phosphatidylserine were taken up most by M2-polarized macrophages, while those without were taken up most by M1-polarized macrophages. Differences in total LPNP uptake were not dependent on endocytosis pathway(s) other than phagocytosis. This work acts as a basis for understanding how the interactions between nanoparticle physicochemical characteristics may act synergistically to facilitate particle uptake.


Assuntos
Lipídeos , Macrófagos , Nanopartículas , Polímeros , Nanopartículas/química , Animais , Macrófagos/metabolismo , Camundongos , Polímeros/química , Polímeros/metabolismo , Lipídeos/química , Tamanho da Partícula , Fagocitose , Endocitose , Fosfatidilserinas/metabolismo , Fosfatidilserinas/química
6.
Macromol Rapid Commun ; 45(12): e2400019, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38544358

RESUMO

Using molecular dynamics simulations, this study investigates the equilibrium properties and flow behaviors of entangled polymer nanoparticle composites (PNCs) within a nanotube. The results show that the density distribution of nanoparticles (NPs), displacement of polymer chains and NPs, and the moduli of PNCs remain relatively unaffected when NP volume fractions (ΦN) ≤0.10. However, the flow behavior of entangled PNCs deviates from the ideal parabolic profile seen in unentangled PNCs, displaying plug-like flow characteristics with a significant platform region, indicating the presence of shear bands. Interestingly, entangled PNCs at intermediate ΦN values undergo a significant alteration in NP distribution under steady flow, resulting in notable NP aggregation. At ΦN = 0.30, a distinct change in the static structure of PNCs occurs, reducing the equilibrium distance between neighboring NPs. Consequently, the motion of both polymer chains and NPs becomes restricted, leading to an increase in the moduli of PNCs resembling solid-like behavior. Additionally, the entangled PNCs experience a complete absence of flow, indicating the entry into a jamming state. This study contributes to the understanding of PNCs flow behavior and provides insights into fundamental aspects and practical implications of PNCs.


Assuntos
Simulação de Dinâmica Molecular , Nanopartículas , Nanotubos , Polímeros , Polímeros/química , Nanopartículas/química , Nanotubos/química , Tamanho da Partícula
7.
Angew Chem Int Ed Engl ; 63(8): e202318533, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38196066

RESUMO

Photochemical regulation provides precise control over enzyme activities with high spatiotemporal resolution. A promising approach involves anchoring "photoswitches" at enzyme active sites to modulate substrate recognition. However, current methods often require genetic mutations and irreversible enzyme modifications for the site-specific anchoring of "photoswitches", potentially compromising the enzyme activities. Herein, we present a pioneering reversible nano-inhibitor based on molecular imprinting technique for bidirectional regulation of intracellular enzyme activity. The nano-inhibitor employs a molecularly imprinted polymer nanoparticle as its body and azobenzene-modified inhibitors ("photoswitches") as the arms. By using a target enzyme as the molecular template, the nano-inhibitor acquires oriented binding sites on its surface, resulting in a high affinity for the target enzyme and non-covalently firm anchoring of the azobenzene-modified inhibitor to the enzyme active site. Harnessing the reversible isomerization of azobenzene units upon exposure to ultraviolet and visible light, the nano-inhibitor achieves bidirectional enzyme activity regulation by precisely docking and undocking inhibitor at the active site. Notably, this innovative approach enables the facile in situ regulation of intracellular endogenous enzymes, such as carbonic anhydrase. Our results represent a practical and versatile tool for precise enzyme activity regulation in complex intracellular environments.


Assuntos
Luz , Impressão Molecular , Compostos Azo/farmacologia , Compostos Azo/química , Impressão Molecular/métodos , Sítios de Ligação
8.
Adv Healthc Mater ; 13(10): e2303615, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38174888

RESUMO

An innovative methodology is presented for synthesizing synthetic polymer nanoparticles (TINPs) as potent tyrosinase inhibitors. This inhibition strategy combines the integration of two distinct functionalities, phenol, and phenylboronic acid, within the TINPs structure. The phenyl group mimics the natural monophenol substrate, forming a strong coordination with the catalytic copper ion, significantly inhibiting tyrosinase activity. Additionally, phenylboronic acid interacts with catechol, another tyrosinase substrate, further reducing enzyme efficiency. The shared benzene ring in phenyl and phenylboronic acid enhances binding to tyrosinase's hydrophobic pocket near its copper active site, contributing to potent inhibition. TINPs exhibit exceptional performance, boasting an impressive IC50 value of 3.5×10-8 m and an inhibition constant of 9.8×10-9 m. Validation of the approach is unequivocally demonstrated through the successful inhibition of tyrosinase activity and melanin production, substantiated in both in vitro and in vivo scenarios. The mechanism of TINP inhibition is elucidated through circular dichroism and Fourier transform infrared spectroscopy. This study introduces a versatile design approach for developing abiotic polymer-based enzyme inhibitors, expanding possibilities in enzyme inhibition research.


Assuntos
Ácidos Borônicos , Monofenol Mono-Oxigenase , Nanopartículas , Cobre/metabolismo , Cobre/farmacologia , Cinética , Monofenol Mono-Oxigenase/química
9.
Pharmaceutics ; 15(9)2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37765331

RESUMO

Pancreatic cancer represents one of the most lethal cancer types worldwide, with a 5-year survival rate of less than 5%. Due to the inability to diagnose it promptly and the lack of efficacy of existing treatments, research and development of innovative therapies and new diagnostics are crucial to increase the survival rate and decrease mortality. Nanomedicine has been gaining importance as an innovative approach for drug delivery and diagnosis, opening new horizons through the implementation of smart nanocarrier systems, which can deliver drugs to the specific tissue or organ at an optimal concentration, enhancing treatment efficacy and reducing systemic toxicity. Varied materials such as lipids, polymers, and inorganic materials have been used to obtain nanoparticles and develop innovative drug delivery systems for pancreatic cancer treatment. In this review, it is discussed the main scientific advances in pancreatic cancer treatment by nano-based drug delivery systems. The advantages and disadvantages of such delivery systems in pancreatic cancer treatment are also addressed. More importantly, the different types of nanocarriers and therapeutic strategies developed so far are scrutinized.

10.
J Vinyl Addit Technol ; 29(4): 795-812, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37546292

RESUMO

Although processing via external stimuli is a promising technique to tune the structure and properties of polymeric materials, the impact of magnetic fields on phase transitions in thermoresponsive polymer solutions is not well-understood. As nanoparticle (NP) addition is also known to impact these thermodynamic and optical properties, synergistic effects from combining magnetic fields with NP incorporation provide a novel route for tuning material properties. Here, the thermodynamic, optical, and rheological properties of aqueous poly(N-isopropyl acrylamide) (PNIPAM) solutions are examined in the presence of hydrophilic silica NPs and magnetic fields, individually and jointly, via Fourier-transform infrared spectroscopy (FTIR), magneto-turbidimetry, differential scanning calorimetry (DSC), and magneto-rheology. While NPs and magnetic fields both reduce the phase separation energy barrier and lower optical transition temperatures by altering hydrogen bonding (H-bonding), infrared spectra demonstrate that the mechanism by which these changes occur is distinct. Magnetic fields primarily alter solvent polarization while NPs provide PNIPAM-NP H-bonding sites. Combining NP addition with field application uniquely alters the solution environment and results in field-dependent rheological behavior that is unseen in polymer-only solutions. These investigations provide fundamental understanding on the interplay of magnetic fields and NP addition on PNIPAM thermoresponsivity which can be harnessed for increasingly complex stimuli-responsive materials.

11.
Polymers (Basel) ; 15(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37571091

RESUMO

Chemical mechanical planarization (CMP) is a wafer-surface-polishing planarization technique based on a wet procedure that combines chemical and mechanical forces to fully flatten materials for semiconductors to be mounted on the wafer surface. The achievement of devices of a small nano-size with few defects and good wafer yields is essential in enabling IC chip manufacturers to enhance their profits and become more competitive. The CMP process is applied to produce many IC generations of nanometer node, or those of even narrower line widths, for a better performance and manufacturing feasibility. Slurry is a necessary supply for CMP. The most critical component in slurry is an abrasive particle which affects the removal rates, uniformity, defects, and removal selectivity for the materials on the wafer surface. The polishing abrasive is the source of mechanical force. Conventional CMP abrasives consist of colloidal silica, fume silica or other inorganic polishing particles in the slurries. We were the first to systematically study nanoparticles of the polymer type applied in CMP, and to compare traditional inorganic and polymer nanoparticles in terms of polishing performance. In particular, the polymer nanoparticle size, shape, solid content dosing ratio, and molecular types were examined. The polishing performance was measured for the polishing removal rates, total defect counts, and uniformity. We found that the polymer nanoparticles significantly improved the total defect counts and uniformity, although the removal rates were lower than the rates obtained using inorganic nanoparticles. However, the lower removal rates of the polymer nanoparticles are acceptable due to the thinner film materials used for smaller IC device nodes, which may be below 10 nm. We also found that the physical properties of polymer nanoparticles, in terms of their size, shape, and different types of copolymer molecules, cause differences in the polishing performance. Meanwhile, we used statistical analysis software to analyze the data on the polishing removal rates and defect counts. This method helps to determine the most suitable polymer nanoparticle for use as a slurry abrasive, and improves the reliability trends for defect counts.

12.
Biosens Bioelectron ; 236: 115381, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37267687

RESUMO

Redox-active molecularly imprinted polymer nanoparticles selective for glyphosate, MIP-Gly NPs, were devised, synthesized, and subsequently integrated onto platinum screen-printed electrodes (Pt-SPEs) to fabricate a chemosensor for selective determination of glyphosate (Gly) without the need for redox probe in the test solution. That was because, ferrocenylmethyl methacrylate was added to the polymerization mixtures during the NPs synthesis so that the resulting MIP-Gly NPs contained covalently immobilized ferrocenyl moieties as the reporting redox ingredient, conferring these NPs with electroactive properties. MIP-Gly NPs of four different compositions were evaluated. The herein described approach represents a simple and effective way to endow MIP NPs with electrochemical reporting capabilities with neither the need to functionalize them post-synthesis nor to use electrochemical mediators present in the tested solution during the analyte determinations. MIP-Gly NPs synthesized using allylamine and squaramide-based monomers appeared most selective to Gly. The Pt-SPEs modified with MIP-Gly NPs were characterized with differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Changes in the DPV peak originating from the oxidation of the ferrocenyl moieties in these MIP-Gly NPs served as the analytical signal. The DPV limit of detection and the linear dynamic concentration range for Gly were 3.7 pM and 25 pM-500 pM, respectively. Moreover, the selectivity of the fabricated chemosensors was sufficiently high to determine Gly successfully in spiked river water samples.


Assuntos
Técnicas Biossensoriais , Impressão Molecular , Nanopartículas , Polímeros Molecularmente Impressos , Polímeros/química , Impressão Molecular/métodos , Técnicas Biossensoriais/métodos , Nanopartículas/química , Eletrodos , Técnicas Eletroquímicas/métodos , Limite de Detecção , Glifosato
13.
ACS Nano ; 17(11): 9826-9849, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37207347

RESUMO

The development of nanovaccines that employ polymeric delivery carriers has garnered substantial interest in therapeutic treatment of cancer and a variety of infectious diseases due to their superior biocompatibility, lower toxicity and reduced immunogenicity. Particularly, stimuli-responsive polymeric nanocarriers show great promise for delivering antigens and adjuvants to targeted immune cells, preventing antigen degradation and clearance, and increasing the uptake of specific antigen-presenting cells, thereby sustaining adaptive immune responses and improving immunotherapy for certain diseases. In this review, the most recent advances in the utilization of stimulus-responsive polymer-based nanovaccines for immunotherapeutic applications are presented. These sophisticated polymeric nanovaccines with diverse functions, aimed at therapeutic administration for disease prevention and immunotherapy, are further classified into several active domains, including pH, temperature, redox, light and ultrasound-sensitive intelligent nanodelivery systems. Finally, the potential strategies for the future design of multifunctional next-generation polymeric nanovaccines by integrating materials science with biological interface are proposed.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Humanos , Neoplasias/terapia , Sistemas de Liberação de Medicamentos , Imunoterapia , Antígenos , Adjuvantes Imunológicos , Nanopartículas/química
14.
Macromol Rapid Commun ; 44(14): e2300013, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37199040

RESUMO

Herein, the photocatalytic generation of an important solar fuel-H2 O2 -by a thiophene-coupled anthraquinone (AQ) and benzotriazole-based donor (D)-acceptor (A) polymer (PAQBTz) nanoparticles is systematically reported. The visible-light active and redox-active D-A type polymer is synthesized employing the Stille coupling polycondensation, and the nanoparticles are obtained by dispersing the PAQBTz polymer and polyvinylpyrrolidone solution, prepared in tetrahydrofuran to water. The polymer nanoparticles (PNPs) produce 1.61 and 1.36 mM mg-1 hydrogen peroxide (H2 O2 ) in the acidic and neutral media, respectively, under AM1.5G simulated sunlight irradiation (λ > 420 nm) with ≈2% modified Solar to Chemical Conversion (SCC) efficiency after 1 h of visible light illumination in acidic condition. The results of the various experiments lay bare the different aspects governing H2 O2 production and indicate the H2 O2 synthesis through the superoxide anion-mediated and anthraquinone-mediated routes.


Assuntos
Nanopartículas , Tiofenos , Hidrogênio , Polímeros , Antraquinonas
15.
ACS Nano ; 17(7): 7017-7034, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36971310

RESUMO

The rapid emergence and spread of vaccine/antibody-escaping variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious challenges to our efforts in combating corona virus disease 2019 (COVID-19) pandemic. A potent and broad-spectrum neutralizing reagent against these escaping mutants is extremely important for the development of strategies for the prevention and treatment of SARS-CoV-2 infection. We herein report an abiotic synthetic antibody inhibitor as a potential anti-SARS-CoV-2 therapeutic agent. The inhibitor, Aphe-NP14, was selected from a synthetic hydrogel polymer nanoparticle library created by incorporating monomers with functionalities complementary to key residues of the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) involved in human angiotensin-converting enzyme 2 (ACE2) binding. It has high capacity, fast adsorption kinetics, strong affinity, and broad specificity in biologically relevant conditions to both the wild type and the current variants of concern, including Beta, Delta, and Omicron spike RBD. The Aphe-NP14 uptake of spike RBD results in strong blockage of spike RBD-ACE2 interaction and thus potent neutralization efficacy against these escaping spike protein variant pseudotyped viruses. It also inhibits live SARS-CoV-2 virus recognition, entry, replication, and infection in vitro and in vivo. The Aphe-NP14 intranasal administration is found to be safe due to its low in vitro and in vivo toxicity. These results establish a potential application of abiotic synthetic antibody inhibitors in the prevention and treatment of the infection of emerging or possibly future SARS-CoV-2 variants.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Enzima de Conversão de Angiotensina 2 , Polímeros , Anticorpos Neutralizantes/farmacologia , Anticorpos Neutralizantes/uso terapêutico , Ligação Proteica , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus
16.
ACS Nano ; 17(1): 70-83, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36534969

RESUMO

The demand for body fat reduction is increasing. However, conventional lipolytic approaches fail to control adipose tissue reduction and cause severe side effects in adjacent nonadipose tissues. A strategy to specifically reduce subcutaneous fat using adipocytolytic polymer nanoparticles in a minimally invasive manner is reported here. The polymer nanoparticles are designed to generate carbon dioxide gas when selectively absorbed by adipocytes. The carbon dioxide gas generated within late endosomes/lysosomes induces adipocytolysis, thereby reducing the number of cells. Localized injection of the adipocytolytic nanoparticles substantially reduces subcutaneous fat in a high-fat diet-induced obese mouse model, without significant changes in hematological or serum biochemical parameters. The adipocytolytic efficacy of the nanoparticles is also evaluated in a porcine model. This strategy addresses the need to develop safe and effective adipocytolytic agents using functional polymer nanoparticles.


Assuntos
Dióxido de Carbono , Nanopartículas , Camundongos , Suínos , Animais , Dióxido de Carbono/farmacologia , Obesidade , Tecido Adiposo , Adipócitos
17.
Adv Healthc Mater ; 12(6): e2202143, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36511367

RESUMO

Osteoarthritis (OA) is a debilitating joint disease affecting nearly 400 million people with no efficient etiological therapies. OA is primarily identified by cartilage destruction, and gradual degeneration of the whole joint would happen when the OA progresses. Hence, cartilage has been identified as the primary therapeutic target of OA. Unfortunately, numerous barriers block the delivery of therapeutic agents into cartilage, including avascular traits and high hardness of the extracellular matrix. Herein, a cartilage-targeting peptide (CAP) modified polyvinylamine (PVAm)- poly (lactic-co-glycolic acid) (PLGA) copolymer (CAP-PVAm-PLGA) is designed, which can form spherical nanoparticles with the r-miR-140 (CPP-NPs). CPP-NPs possessed enhanced mechanical properties due to the introduction of PLGA to vehicles. Meanwhile, CAP endowed the cartilage targeting which facilitated CPP-NPs localization in cartilage. With such dual advantages, CPP-NPs exhibited outstanding penetrability and accumulation in cartilage even subchondral bone, and can penetrate to a depth of 1000 µm into human cartilage. The degeneration area of cartilage is reduced by 65% and synovial inflammation score by 80% in OA mice, and the microarchitecture of subchondral bone is also ameliorated. These studies established a promising platform for therapeutic RNA delivery in OA therapy that overcame the cartilage barriers.


Assuntos
Cartilagem Articular , MicroRNAs , Osteoartrite , Humanos , Camundongos , Animais , Polímeros/uso terapêutico , Cartilagem , Peptídeos/uso terapêutico , Osteoartrite/tratamento farmacológico
18.
Drug Deliv Transl Res ; 13(2): 568-579, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36058987

RESUMO

Cutaneous malignant melanoma is fastest-growing cancer in white populations with a large majority of dermal cancer death. The activity of vascular endothelial growth factors (VEGFs) results in the signaling of a variety of downstream intracellular pathways that ultimately leads to cell activation, proliferation, migration, and angiogenesis. VEGF inhibitors such as bevacizumab are widely used in chemotherapy with systemic administration, which in many cases is associated with a variety of side effects. Here, we designed and synthesized a lipid-polymer nanoparticle for local administration of bevacizumab. Drug release, dermal absorption, and the effects of synthesized nanoparticles containing bevacizumab on cell proliferation and in vitro and in vivo angiogenesis were investigated. Encapsulating bevacizumab in the synthesized nanoparticles resulted in a significant increase in its dermal absorption compared to free bevacizumab. Also, the suppressor effects of bevacizumab encapsulated in the synthesized nanoparticle on cell proliferation and angiogenesis were significantly more than those of free bevacizumab. Our findings indicate the remarkable effects of lipid-polymer nanoparticles in dermal absorption and in maintaining bevacizumab bioactivity, suggesting therapeutic benefits of local bevacizumab administration for angiogenesis-related disorders such as cutaneous melanoma. Chitosan nanoparticles containing bevacizumab antibody were synthesized by ion exchange method, and finally, these nanoparticles were coated with lipid (Lip-Chi-Bev NPs). In this study, the effect of synthesized nanoparticles on dermal absorption of bevacizumab was evaluated and its potential in inhibiting angiogenesis was evaluated by in vitro and in vivo models.


Assuntos
Quitosana , Melanoma , Nanopartículas , Neoplasias Cutâneas , Humanos , Bevacizumab , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Lipídeos , Inibidores da Angiogênese/farmacologia , Melanoma Maligno Cutâneo
19.
Int J Mol Sci ; 23(22)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36430411

RESUMO

The mechanism of RNA interference (RNAi) could represent a breakthrough in the therapy of all diseases that arise from a gene defect or require the inhibition of a specific gene expression. In particular, small interfering RNA (siRNA) offers an attractive opportunity to achieve a new milestone in the therapy of human diseases. The limitations of siRNA, such as poor stability, inefficient cell uptake, and undesired immune activation, as well as the inability to specifically reach the target tissue in the body, can be overcome by further developments in the field of nanoparticulate drug delivery. Therefore, types of surface modified siRNA nanoparticles are presented and illustrate how a more efficient and safer distribution of siRNA at the target site is possible by modifying the surface properties of nanoparticles with antibodies. However, the development of such efficient and safe delivery strategies is currently still a major challenge. In consideration of that, this review article aims to demonstrate the function and targeted delivery of siRNA nanoparticles, focusing on the surface modification via antibodies, various lipid- and polymer-components, and the therapeutic effects of these delivery systems.


Assuntos
Nanopartículas , Polímeros , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Sistemas de Liberação de Medicamentos , Anticorpos , Lipídeos
20.
Theranostics ; 12(16): 6883-6897, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276646

RESUMO

Rationale: Immunogenic cell death (ICD)-associated immunogenicity evoked through reactive oxygen species (ROS) is an efficient way to fight against the immune-dysfunctional microenvironment, so as to provoke potent anti-tumor immunity. However, the unknown ROS dose during cancer therapies may induce adverse immune responses (e.g., insufficient ICD, toxicity toward normal tissues or immune system). Methods: Herein, we developed a pyrido pyrazine - thiophene based semiconducting polymer as novel near-infrared (NIR) organic afterglow nanoparticles for the real-time visualization of self-generated ROS, during photodynamic-mediated immunogenic cell death. Specifically, we introduced the strong "acceptor" (pyrido pyrazine) into thiophene based semiconducting polymer to redshift emission wavelength, and further modulate the "donor" to afford more afterglow reaction sites and reducing ΔEst, so as to enhance luminescence intensity. Results: The semiconducting polymer-based afterglow nanoparticles exhibit strong afterglow emission with longer-wavelength emission (> 800 nm), compared with the reported organic afterglow nanoparticles (e.g., MEHPPV, PFODBT or Chlorin, < 690 nm), which endows this afterglow nanoparticles with a greatly improvement of signal to noise ratio. Moreover, the photodynamic effect of this afterglow nanoparticles can induce immunogenic cell death of cancer cells and further cause immune responses in mice. Conclusions: The NIR afterglow signal presents a good relationship with ROS generation, immunogenic cell death and outcome of treatment. Therefore, it was able to provide a non-invasive tool for predicting the degree of ICD that occurs during ROS-mediated cancer therapy and may contribute to precise immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/uso terapêutico , Polímeros/uso terapêutico , Tiofenos/uso terapêutico , Pirazinas , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico
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