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1.
Int J Mol Sci ; 25(18)2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39337638

RESUMEN

A new green water treatment agent, a poly(aspartic acid)-modified polymer (PASP/5-AVA), was synthesized using polysuccinimide and 5-aminovaleric acid (5-AVA) in a hybrid system. The structure was characterized, and the scale and corrosion inhibition performance were carried out with standard static scale inhibition and electrochemical methods, respectively. The mechanism was explored using XRD, XPS, SEM, and quantum chemistry calculations. The results indicated that PASP/5-AVA exhibited better scale and corrosion inhibition performance than PASP and maintained efficacy and thermal stability of the scale inhibition effect for a long time. Mechanistic studies indicated that PASP/5-AVA interferes with the normal generation of CaCO3 and CaSO4 scales through lattice distortion and dispersion, respectively; the combined effect of an alkaline environment and terminal electron-withdrawing -COOH groups can induce the stable C- ionic state formation in -CH2- of the extended side chain, thus enhancing its chelating ability for Ca2+ ions. At the same time, the extension of the side chain length also enhances the adsorption ability of the agent on the metal surface, forming a thick film and delaying the corrosion of the metal surface. This study provides the necessary theoretical reference for the design of green scale and corrosion agents.


Asunto(s)
Péptidos , Corrosión , Péptidos/química , Péptidos/síntesis química , Tecnología Química Verde/métodos , Purificación del Agua/métodos , Polímeros/química , Polímeros/síntesis química , Adsorción
2.
ACS Nano ; 18(39): 26839-26847, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39287594

RESUMEN

Diblock oligomeric peptide-polymer amphiphiles (PPAs) are biohybrid materials that offer versatile functionality by integrating the sequence-dependent properties of peptides with the synthetic versatility of polymers. Despite their potential as biocompatible materials, the rational design of PPAs for assembly into multichain nanoparticles remains challenging due to the complex intra- and intermolecular interactions emanating from the polymer and peptide segments. To systematically explore the impact of monomer composition on nanoparticle assembly, PPAs were synthesized with a random coil peptide (XTEN2) and oligomeric alkyl acrylates with different side chains: ethyl, tert-butyl, n-butyl, and cyclohexyl. Experimental characterization using electron and atomic force microscopies demonstrated that the tail hydrophobicity impacted accessible morphologies. Moreover, the characterization of different assembly protocols (i.e., bath sonication and thermal annealing) revealed that certain tail compositions provide access to kinetically trapped assemblies. All-atom molecular dynamics simulations of micelle formation unveiled key interactions and differences in core hydration, dictating the PPA assembly behavior. These findings highlight the complexity of PPA assembly dynamics and serve as valuable benchmarks to guide the design of PPAs for a variety of applications, including catalysis, mineralization, targeted sequestration, antimicrobial activity, and cargo transportation.


Asunto(s)
Simulación de Dinámica Molecular , Péptidos , Polímeros , Péptidos/química , Péptidos/síntesis química , Péptidos/farmacología , Polímeros/química , Polímeros/síntesis química , Interacciones Hidrofóbicas e Hidrofílicas , Micelas , Tensoactivos/química , Tensoactivos/síntesis química , Tamaño de la Partícula , Nanopartículas/química
3.
ACS Appl Mater Interfaces ; 16(39): 51876-51898, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39311719

RESUMEN

Polyphosphoesters (PPEs) represent an innovative class of biodegradable polymers, with the phosphate ester serving as the core repeating unit of their polymeric backbone. Recently, biomaterials derived from functionalized PPEs have garnered significant interest in biomedical applications because of their commendable biocompatibility, biodegradability, and the capacity for functional modification. This review commences with a brief overview of synthesis methodologies and the distinctive properties of PPEs, including thermoresponsiveness, degradability, stealth effect, and biocompatibility. Subsequently, the review delves into the latest applications of PPEs-based nanocarriers for drug or gene delivery and PPEs-based polymeric prodrugs and scaffolds in the biomedical field, presenting several illustrative examples for each application. By encapsulating the advancements of recent years, this review aims to offer an enhanced understanding and serve as a reference for the synthesis and biomedical applications of functional PPEs.


Asunto(s)
Materiales Biocompatibles , Polímeros , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Humanos , Polímeros/química , Polímeros/síntesis química , Portadores de Fármacos/química , Portadores de Fármacos/síntesis química , Animales , Ésteres/química
4.
Bioorg Chem ; 152: 107711, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39178706

RESUMEN

Cancer immunotherapy leverages the immune system's inherent capacity to combat malignancies. However, effective stimulation of Dendritic cells (DCs) is challenging due to their limited distribution and the immune-suppressive tumor microenvironment. Thus, targeting mannose receptors, which are highly expressed on DCs, represents a promising strategy. This study investigates the development of mannose-based glycopolymer nanoparticles to induce activation of DCs through enhanced antigen presentation. A novel ABA-type triblock bioconjugated glycopolymer (PMn-b-PCL-b-PMn), which mimics mannose was synthesized. This polymer was further modified with Dihexadecyldimethylammonium bromide (DHDAB) to prepare cationic nanoparticles (CMNP) for gene delivery of pCMV-TRP2, an antigenic marker for both melanoma and glioblastoma. The immune response generated by CMNP and the CMNP-TRP2 polyplex was compared to an untreated control following subcutaneous injection in mice. Post-injection cytometric analysis revealed robust DC activation and increased T-cell populations in secondary lymphoid organs, including the spleen and lymph nodes. These findings suggest that CMNP can serve as a potent biomimicking vaccination vehicle against cancer, enhancing the immune response through targeted DCs activation.


Asunto(s)
Células Dendríticas , Inmunoterapia , Manosa , Ratones Endogámicos C57BL , Nanopartículas , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Nanopartículas/química , Animales , Manosa/química , Manosa/farmacología , Ratones , Polímeros/química , Polímeros/farmacología , Polímeros/síntesis química , Estructura Molecular , Humanos , Femenino , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga
5.
Int J Mol Sci ; 25(15)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39125990

RESUMEN

The terpolymers of N-vinylpyrrolidone (VP) with acrylic acid and triethylene glycol methacrylate were synthesized with more than 90% yield by radical copolymerization in ethanol from monomeric mixtures of different molar composition (98:2:2, 95:5: 2 and 98:2:5) and their monomer composition, absolute molecular masses and hydrodynamic radii in aqueous media were determined. Using the MTT test, these terpolymers were established to be low toxic for non-tumor Vero cells and HeLa tumor cells. Polymer compositions of hydrophobic dye methyl pheophorbide a (MPP) based on studied terpolymers and linear polyvinylpyrrolidone (PVP) were obtained and characterized in water solution. Quantum-chemical modeling of the MPP-copolymer structures was conducted, and the possibility of hydrogen bond formation between terpolymer units and the MPP molecule was shown. Using fluorescence microscopy, the accumulation and distribution of polymer particles in non-tumor (FetMSC) and tumor (HeLa) cells was studied, and an increase in the accumulation of MPP with both types of particles was found.


Asunto(s)
Acrilatos , Humanos , Animales , Chlorocebus aethiops , Acrilatos/química , Células Vero , Células HeLa , Sistemas de Liberación de Medicamentos , Pirrolidinonas/química , Metacrilatos/química , Polietilenglicoles/química , Polímeros/química , Polímeros/síntesis química , Supervivencia Celular/efectos de los fármacos
6.
Chem Commun (Camb) ; 60(64): 8427-8430, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39034822

RESUMEN

A conjugated polymer, P4TTD-DPP, based on tetra-fused isoindigo-alt-diketopyrrolopyrrole, has been synthesized as a photothermal therapeutic nanotransducer within the near-infrared-II (NIR-II) window. P4TTD-DPP exhibits a notable mass extinction coefficient of 62.8 L g-1 cm-1 at 1064 nm. Additionally, P4TTD-DPP nanoparticles demonstrate remarkable photothermal conversion efficiency of 91.5% at 1064 nm and exhibit excellent anticancer efficacy under photothermal conditions.


Asunto(s)
Antineoplásicos , Rayos Infrarrojos , Polímeros , Polímeros/química , Polímeros/farmacología , Polímeros/síntesis química , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Supervivencia Celular/efectos de los fármacos , Nanopartículas/química , Indoles/química , Indoles/farmacología , Terapia Fototérmica , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Pirroles/química , Pirroles/farmacología , Fototerapia , Ratones , Estructura Molecular , Animales
7.
Macromol Rapid Commun ; 45(19): e2400309, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39012218

RESUMEN

Cryopreservation is a common way for long-term storage of therapeutical proteins, erythrocytes, and mammalian cells. For cryoprotection of these biosamples to keep their structural integrity and biological activities, it is essential to incorporate highly efficient cryoprotectants. Currently, permeable small molecular cryoprotectants such as glycerol and dimethyl sulfoxide dominate in cryostorage applications, but they are harmful to cells and human health. As acting in the extracellular space, membrane-impermeable macromolecular cryoprotectants, which exert remarkable membrane stabilization against cryo-injury and are easily removed post-thaw, are promising candidates with biocompatibility and feasibility. Water-soluble hydroxyl-containing polymers such as poly(vinyl alcohol) and polyol-based polymers are potent ice recrystallization inhibitors, while polyampholytes, polyzwitterions, and bio-inspired (glyco)polypeptides can significantly increase post-thaw recovery with reduced membrane damages. In this review, the synthetic macromolecular cryoprotectants are systematically summarized based on their synthesis routes, practical utilities, and cryoprotective mechanisms. It provides a valuable insight in development of highly efficient macromolecular cryoprotectants with valid ice recrystallization inhibition activity for highly efficient and safe cryopreservation of cells.


Asunto(s)
Criopreservación , Crioprotectores , Sustancias Macromoleculares , Criopreservación/métodos , Crioprotectores/química , Crioprotectores/farmacología , Humanos , Sustancias Macromoleculares/química , Sustancias Macromoleculares/farmacología , Sustancias Macromoleculares/síntesis química , Polímeros/química , Polímeros/farmacología , Polímeros/síntesis química , Animales
8.
Macromol Biosci ; 24(10): e2400168, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39052313

RESUMEN

Poly (ß-amino ester) (PBAE) is a class of biodegradable polymers containing ester bonds in their main chain, extensively investigated as cationic polymer carriers for siRNA. Most current PBAE carriers rely on termination with hydrophilic or charged amines. In this study, a polymer platform consisting of 168 PBAE polymers with hydrophobic alkyl chain terminals is constructed through sequential aza-Michael addition. A large number of effective carriers are identified through in vitro screening of the PBAE platform for siLuc delivery to HeLa-Luc cells. Specifically, PA8-C6 and PA8-C8 achieve remarkable gene knockdown efficacies of up to 80% with low cytotoxicity. Certain materials from the PA2 and PA5 series demonstrate potent siRNA delivery capabilities associated with elevated cytotoxicity. The pKa value of PBAE is predominantly determined by the hydrophilic amine side chains rather than the end-capping groups. A pKa range of ≈6.2-6.5 may contribute to the excellent delivery capability for PA8 series carriers. The co-formulation of PBAE carriers with helper lipids leads to the reduced size and surface charges of the polyplex NPs with siRNA, consequently decreasing the cytotoxicity and enhancing siRNA delivery efficacy. These findings hold significant implications for the development of novel degradable polymer carriers for siRNA delivery.


Asunto(s)
Polímeros , ARN Interferente Pequeño , ARN Interferente Pequeño/química , ARN Interferente Pequeño/farmacología , Humanos , Células HeLa , Polímeros/química , Polímeros/síntesis química , Interacciones Hidrofóbicas e Hidrofílicas , Portadores de Fármacos/química , Portadores de Fármacos/síntesis química , Nanopartículas/química
9.
Anal Chim Acta ; 1317: 342881, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39029999

RESUMEN

A molecularly imprinting polymer (MIP) carrier with pH-responsivity was designed to construct a drug delivery system (DDS) focusing on controlled and sustainable capecitabine (CAPE) release. The pH-responsive characteristic was achieved by the functionalization of SiO2 substrate with 4-formylphenylboronic acid, accompanied by the introduction of fluorescein isothiocyanate for the visualization of the intracellular localization of the nanocarrier. Experimental results indicated that CAPE was adsorbed onto the drug carrier with satisfactory encapsulation efficiency. The controlled release of CAPE was realized based on the break of borate ester bonds between -B(OH)2 and cis-diols in the weakly acidic environment. Density functional theory computations were conducted to investigate the adsorption/release mechanism. Moreover, in vitro experiments confirmed the good biocompatibility and ideal inhibition efficiency of the developed DDS. The MIP can act as an eligible carrier and exhibits the great potential in practical applications for tumor treatment.


Asunto(s)
Capecitabina , Portadores de Fármacos , Polímeros Impresos Molecularmente , Capecitabina/química , Concentración de Iones de Hidrógeno , Portadores de Fármacos/química , Polímeros Impresos Molecularmente/química , Humanos , Liberación de Fármacos , Antimetabolitos Antineoplásicos/química , Preparaciones de Acción Retardada/química , Supervivencia Celular/efectos de los fármacos , Teoría Funcional de la Densidad , Polímeros/química , Polímeros/síntesis química
10.
Carbohydr Res ; 542: 109200, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38964015

RESUMEN

The polymeric nanoparticles (PNPs) loaded with prednisolone were developed to exhibit pH-responsive properties owing to the attachment of a hydrazone linkage between the copolymer chitosan and mPEG. In the diseased cellular environment, the hydrazone bond tends to break due to reduced pH, leading to the release of the drug from the PNPs at the required site of action. The fabricated PNPs exhibit spherical morphology, optimum size (∼200 nm), negative surface charge, and monodispersed particle size distribution. The encapsulation efficiency of the PNPs was determined to be 71.1 ± 0.79 % and two experiments (polymer weight loss and drug release) confirmed the pH-responsive properties of the PNPs. The cellular study cytotoxicity assay showed biocompatibility of PNPs and drug molecule-mediated toxicity to A549 cells. The ligand atrial natriuretic peptide-attached PNPs internalized into A549 cells via natriuretic peptide receptor-A to achieve target specificity. The PNPs cytotoxicity and pH-response medicated inflammation reduction functionality was studied in inflammation-induced RAW264.7 cell lines. The study observed the PNPs effectively reduced the inflammatory mediators NO and ROS levels in RAW264.7. The results showed that pH-responsive properties of PNPs and this novel fabricated delivery system effectively treat inflammatory and cancer diseases.


Asunto(s)
Quitosano , Química Clic , Nanopartículas , Quitosano/química , Quitosano/farmacología , Concentración de Iones de Hidrógeno , Humanos , Ratones , Animales , Nanopartículas/química , Células RAW 264.7 , Células A549 , Portadores de Fármacos/química , Portadores de Fármacos/síntesis química , Sistemas de Liberación de Medicamentos , Tamaño de la Partícula , Polímeros/química , Polímeros/síntesis química , Polímeros/farmacología , Liberación de Fármacos , Prednisolona/química , Prednisolona/farmacología , Supervivencia Celular/efectos de los fármacos
11.
ACS Appl Mater Interfaces ; 16(29): 37545-37554, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38985802

RESUMEN

Successful therapeutic delivery of siRNA with polymeric nanoparticles seems to be a promising but not vastly understood and complicated goal to achieve. Despite years of research, no polymer-based delivery system has been approved for clinical use. Polymers, as a delivery system, exhibit considerable complexity and variability, making their consistent production a challenging endeavor. However, a better understanding of the polymerization process of polymer excipients may improve the reproducibility and material quality for more efficient use in drug products. Here, we present a combination of Design of Experiment and Python-scripted data science to establish a prediction model, from which important parameters can be extracted that influence the synthesis results of polybeta-amino esters (PBAEs), a common type of polymer used preclinically for nucleic acid delivery. We synthesized a library of 27 polymers, each one at different temperatures with different reaction times and educt ratios using an orthogonal central composite (CCO-) design. This design allowed a detailed characterization of factor importance and interactions using a very limited number of experiments. We characterized the polymers by analyzing the resulting composition by 1H-NMR and the size distribution by GPC measurements. To further understand the complex mechanism of block polymerization in a one-pot synthesis, we developed a Python script that helps us to understand possible step-growth steps. We successfully developed and validated a predictive response surface and gathered a deeper understanding of the synthesis of polyspermine-based amphiphilic PBAEs.


Asunto(s)
Polímeros , Espermina , Polímeros/química , Polímeros/síntesis química , Espermina/química , Nanopartículas/química , Polimerizacion
12.
Angew Chem Int Ed Engl ; 63(38): e202408670, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-38943429

RESUMEN

Peptide folding is a dynamic process driven by non-covalent cross-linking leading to functional nanostructures for essential biochemical activities. However, replicating this process in synthetic systems is challenging due to the difficulty in mimicking nature's real-time regulation of non-covalent crosslinking for single-chain polymer folding. Here, we address this by employing anionic dithiol building blocks to create macrocyclic disulfides as non-covalent crosslinkers that adapted to the folding process. Initially, small macrocycles facilitated a low degree folding of a polycation. Then, this preorganized structure catalysed the production of larger macrocycles that enhanced the folding conversely. The self-adaptive synthesis was verified through the encapsulation of an anticancer drug, showing an updated production distribution of non-covalent crosslinkers and maximizing drug-loading efficiency against drug-resistant cancer in vitro. Our research advances the understanding of molecular systems by exploring species evolution via the structural dynamics of polymer folding. Additionally, adaptive synthesis enables controlled, sequential folding of synthetic polymers, with the potential to mimic protein functions.


Asunto(s)
Polímeros , Polímeros/química , Polímeros/síntesis química , Disulfuros/química , Humanos , Pliegue de Proteína , Reactivos de Enlaces Cruzados/química , Reactivos de Enlaces Cruzados/síntesis química , Estructura Molecular
13.
Chem Asian J ; 19(17): e202400453, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-38878271

RESUMEN

Temperature-responsive hydrogels, or thermogels, have emerged as a leading platform for sustained delivery of both small molecule drugs and macromolecular biologic therapeutics. Although thermogel properties can be modulated by varying the polymer's hydrophilic-hydrophobic balance, molecular weight and degree of branching, varying the supramolecular donor-acceptor interactions on the polymer remains surprisingly overlooked. Herein, to study the influence of enhanced hydrogen bonding on thermogelation, we synthesized a family of amphiphilic polymers containing urea and urethane linkages using quinuclidine as an organocatalyst. Our findings showed that the presence of strongly hydrogen bonding urea linkages significantly enhanced polymer hydration in water, in turn affecting hierarchical polymer self-assembly and macroscopic gel properties such as sol-gel phase transition temperature and gel stiffness. Additionally, analysis of the sustained release profiles of Aflibercept, an FDA-approved protein biologic for anti-angiogenic treatment, showed that urea bonds on the thermogel were able to significantly alter the drug release mechanism and kinetics compared to usage of polyurethane gels of similar composition and molecular weight. Our findings demonstrate the unrealized possibility of modulating gel properties and outcomes of sustained drug delivery through judicious variation of hydrogen bonding motifs on the polymer structure.


Asunto(s)
Hidrogeles , Temperatura , Hidrogeles/química , Hidrogeles/síntesis química , Polímeros/química , Polímeros/síntesis química , Uretano/química , Factor A de Crecimiento Endotelial Vascular/química , Factor A de Crecimiento Endotelial Vascular/metabolismo , Liberación de Fármacos , Enlace de Hidrógeno , Humanos , Sistemas de Liberación de Medicamentos , Poliuretanos/química , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/farmacología
14.
ACS Appl Mater Interfaces ; 16(22): 28104-28117, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38769350

RESUMEN

Sonodynamic therapy (SDT), which involves the activation of sonosensitizers to generate cytotoxic reactive oxygen species under ultrasound irradiation, is a promising noninvasive modality for cancer treatment. However, the clinical translational application of SDT is impeded by the lack of efficient sonosensitizers, the inefficient accumulation of sonosensitizers at tumor sites, and the complicated immunosuppressive tumor microenvironment. Herein, we developed a facilely synthesized multifunctional porous organic polymer nanosonosensitizer (mHM@HMME) for enhanced SDT. Specifically, mHM@HMME nanosonosensitizers were prepared by incorporating chemotherapeutic mitoxantrone into the one-step synthesis process of disulfide bond containing porous organic polymers, followed by loading with organic sonosensitizer (HMME) and camouflaging with a cancer cell membrane. Due to the cancer cell membrane camouflage, this multifunctional mHM@HMME nanosonosensitizer showed prolonged blood circulation and tumor targeting aggregation. Under ultrasound irradiation, the mHM@HMME nanosonosensitizer exhibited a satisfactory SDT performance both in vitro and in vivo. Moreover, the potent SDT combined with glutathione-responsive drug release in tumor cells induced robust immunogenic cell death to enhance the antitumor effect of SDT in turn. Overall, this facilely synthesized multifunctional mHM@HMME nanosonosensitizer shows great potential application in enhanced SDT.


Asunto(s)
Polímeros , Terapia por Ultrasonido , Animales , Ratones , Humanos , Porosidad , Terapia por Ultrasonido/métodos , Polímeros/química , Polímeros/síntesis química , Polímeros/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Ratones Endogámicos BALB C , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Línea Celular Tumoral , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Femenino
15.
Eur J Med Chem ; 273: 116507, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38776806

RESUMEN

Careful recruitment of the components of the HDAC inhibitory template culminated in veliparib-based anilide 8 that elicited remarkable cell growth inhibitory effects against HL-60 cell lines mediated via dual modulation of PARP [(IC50 (PARP1) = 0.02 nM) and IC50 (PARP2) = 1 nM)] and HDACs (IC50 value = 0.05, 0.147 and 0.393 µM (HDAC1, 2 and 3). Compound 8 downregulated the expression levels of signatory biomarkers of PARP and HDAC inhibition. Also, compound 8 arrested the cell cycle at the G0/G1 phase and induced autophagy. Polymer nanoformulation (mPEG-PCl copolymeric micelles loaded with compound 8) was prepared by the nanoprecipitation technique. The mPEG-PCL diblock copolymer was prepared by ring-opening polymerization method using stannous octoate as a catalyst. The morphology of the compound 8@mPEG-PCL was examined using TEM and the substance was determined to be monodispersed, spherical in form, and had an average diameter of 138 nm. The polymer nanoformulation manifested pH-sensitive behaviour as a greater release of compound 8 was observed at 6.2 pH as compared to 7.4 pH mimicking physiological settings. The aforementioned findings indicate that the acidic pH of the tumour microenvironment might stimulate the nanomedicine release which in turn can attenuate the off-target effects precedentially claimed to be associated with HDAC inhibitors.


Asunto(s)
Antineoplásicos , Bencimidazoles , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Polietilenglicoles , Humanos , Concentración de Iones de Hidrógeno , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Bencimidazoles/química , Bencimidazoles/farmacología , Bencimidazoles/síntesis química , Proliferación Celular/efectos de los fármacos , Polietilenglicoles/química , Células HL-60 , Nanopartículas/química , Estructura Molecular , Micelas , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Poliésteres/química , Poliésteres/farmacología , Poliésteres/síntesis química , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/síntesis química , Polímeros/química , Polímeros/farmacología , Polímeros/síntesis química
16.
Org Biomol Chem ; 22(24): 4958-4967, 2024 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-38819437

RESUMEN

Development of biocompatible nanomaterials with mitochondria-targeting and multimodal therapeutic activities is important for cancer treatment. Herein, we designed and synthesized a multifunctional pyrrole-based nanomaterial with photothermal effects and mitochondria-targeting properties from polypyrrole and the pro-apoptotic peptide KLA. Different from traditional strategies for the preparation of PPy nanoparticles, we innovatively used the KLA peptide as the template and CuCl2 as the catalyst to trigger the oxidative polymerization of pyrrole for PPy-KLA-Cu nanoparticle formation. Besides, due to the presence of mixed-valence Cu(I)/Cu(II) states, PPy-KLA-Cu nanoparticles also exhibited multienzyme-like activities, such as peroxidase, ascorbate oxidase and glutathione peroxidase activities, which can be exploited to elevate the intracellular ROS level and simultaneously consume GSH in cancer cells. More importantly, the heat generated by PPy-KLA-Cu nanoparticles from NIR irradiation could enhance the nanozymatic activities for ROS elevation and increase the KLA-induced anticancer activity via mitochondrial dysfunction, realizing multimodal treatment of cancer cells with improved therapeutic efficacy.


Asunto(s)
Antineoplásicos , Apoptosis , Mitocondrias , Polímeros , Pirroles , Pirroles/química , Pirroles/farmacología , Pirroles/síntesis química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Humanos , Polímeros/química , Polímeros/farmacología , Polímeros/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Catálisis , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Especies Reactivas de Oxígeno/metabolismo , Cobre/química , Cobre/farmacología , Nanoestructuras/química , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/patología
17.
J Am Chem Soc ; 146(20): 13836-13845, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38717976

RESUMEN

Hydrogels hold significant promise as drug delivery systems due to their distinct advantage of sustained localized drug release. However, the challenge of regulating the initial burst release while achieving precise control over degradation and drug-release kinetics persists. Herein, we present an ABA-type triblock copolymer-based hydrogel system with precisely programmable degradation and release kinetics. The resulting hydrogels were designed with a hydrophilic poly(ethylene oxide) midblock and a hydrophobic end-block composed of polyethers with varying ratios of ethoxyethyl glycidyl ether and tetrahydropyranyl glycidyl ether acetal pendant possessing different hydrolysis kinetics. This unique side-chain strategy enabled us to achieve a broad spectrum of precise degradation and drug-release profiles under mildly acidic conditions while maintaining the cross-linking density and viscoelastic modulus, which is unlike the conventional polyester-based backbone degradation system. Furthermore, programmable degradation of the hydrogels and release of active therapeutic agent paclitaxel loaded therein are demonstrated in an in vivo mouse model by suppressing tumor recurrence following surgical resection. Tuning of the fraction of two acetal pendants in the end-block provided delicate tailoring of hydrogel degradation and the drug release capability to achieve the desired therapeutic efficacy. This study not only affords a facile means to design hydrogels with precisely programmable degradation and release profiles but also highlights the critical importance of aligning the drug release profile with the target disease.


Asunto(s)
Liberación de Fármacos , Hidrogeles , Hidrogeles/química , Hidrogeles/síntesis química , Animales , Ratones , Acetales/química , Paclitaxel/química , Paclitaxel/farmacocinética , Éteres/química , Polietilenglicoles/química , Polímeros/química , Polímeros/síntesis química , Portadores de Fármacos/química
18.
Biomacromolecules ; 25(5): 3122-3130, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38696355

RESUMEN

Synthesis of polysaccharide-b-polypeptide block copolymers represents an attractive goal because of their promising potential in delivery applications. Inspired by recent breakthroughs in N-carboxyanhydride (NCA) ring-opening polymerization (ROP), we present an efficient approach for preparation of a dextran-based macroinitiator and the subsequent synthesis of dextran-b-polypeptides via NCA ROP. This is an original approach to creating and employing a native polysaccharide macroinitiator for block copolymer synthesis. In this strategy, regioselective (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of the sole primary alcohol located at the C-6 position of the monosaccharide at the nonreducing end of linear dextran results in a carboxylic acid. This motif is then transformed into a tetraalkylammonium carboxylate, thereby generating the dextran macroinitiator. This macroinitiator initiates a wide range of NCA monomers and produces dextran-b-polypeptides with a degree of polymerization (DP) of the polypeptide up to 70 in a controlled manner (D < 1.3). This strategy offers several distinct advantages, including preservation of the original dextran backbone structure, relatively rapid polymerization, and moisture tolerance. The dextran-b-polypeptides exhibit interesting self-assembly behavior. Their nanostructures have been investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and adjustment of the structure of block copolymers allows self-assembly of spherical micelles and worm-like micelles with varied diameters and aspect ratios, revealing a range of diameters from 60 to 160 nm. Moreover, these nanostructures exhibit diverse morphologies, including spherical micelles and worm-like micelles, enabling delivery applications.


Asunto(s)
Dextranos , Péptidos , Polimerizacion , Dextranos/química , Péptidos/química , Péptidos/síntesis química , Polímeros/química , Polímeros/síntesis química , Óxidos N-Cíclicos/química , Anhídridos/química , Polisacáridos/química , Micelas
19.
Macromol Rapid Commun ; 45(14): e2400079, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38662380

RESUMEN

Protein-polymer conjugates and polymeric nanomaterials hold great promise in many applications including biomaterials, medicine, or nanoelectronics. In this work, the first polymerization-induced self-assembly (PISA) approach performed in aqueous medium enabling protein-polymer conjugates and nanoparticles entirely composed of amino acids is presented by using ring-opening polymerization (ROP). It is indeed shown that aqueous ring-opening polymerization-induced self-assembly (ROPISA) can be used with protein or peptidic macroinitiators without prior chemical modification and afford the simple preparation of nanomaterials with protein-like property, for example, to implement biomimetic thermoresponsivity in drug delivery.


Asunto(s)
Nanopartículas , Péptidos , Polimerizacion , Agua , Péptidos/química , Nanopartículas/química , Agua/química , Polímeros/química , Polímeros/síntesis química , Proteínas/química , Tamaño de la Partícula , Estructura Molecular
20.
Anticancer Agents Med Chem ; 24(13): 969-981, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38616743

RESUMEN

BACKGROUND: Limited chemotherapy efficacy and cancer stem cells (CSCs)-induced therapeutic resistance are major difficulties for tumour treatment. Adopting more efficient therapies to eliminate bulk-sensitive cancer cells and resistant CSCs is urgently needed. METHODS: Based on the potential and functional complementarity of gold and silver nanoparticles (AuNPs or AgNPs) on tumour treatment, bimetallic NPs (alloy) have been synthesized to obtain improved or even newly emerging bioactivity from a combination effect. This study reported a facile, green and economical preparation of Au-Ag alloy NPs using biocompatible polydopamine (PDA) as a reductant, capping, stabilizing and hydrophilic agent. RESULTS: These alloy NPs were quasi-spherical with rough surfaces and recorded in diameters of 80 nm. In addition, these alloy NPs showed good water dispersity, stability and photothermal effect. Compared with monometallic counterparts, these alloy NPs demonstrated a dramatically enhanced cytotoxic/pro-apoptotic/necrotic effect towards bulk-sensitive MCF-7 and MDA-MB-231 cells. The underlying mechanism regarding the apoptotic action was associated with a mitochondria-mediated pathway, as evidenced by Au3+/Ag+ mediated Mitochondria damage, ROS generation, DNA fragmentation and upregulation of certain apoptotic-related genes (Bax, P53 and Caspase 3). Attractively, these Au-Ag alloy NPs showed a remarkably improved inhibitory effect on the mammosphere formation capacity of MCF-7 CSCs. CONCLUSION: All the positive results were attributed to incorporated properties from Au, Ag and PDA, the combination effect of chemotherapy and photothermal therapy and the nano-scaled structure of Au-Ag alloy NPs. In addition, the high biocompatibility of Au-Ag alloy NPs supported them as a good candidate in cancer therapy.


Asunto(s)
Antineoplásicos , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Oro , Tecnología Química Verde , Indoles , Nanopartículas del Metal , Células Madre Neoplásicas , Polímeros , Plata , Humanos , Indoles/química , Indoles/farmacología , Indoles/síntesis química , Oro/química , Oro/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Polímeros/química , Polímeros/farmacología , Polímeros/síntesis química , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Aleaciones/química , Aleaciones/farmacología , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Relación Estructura-Actividad , Células MCF-7 , Estructura Molecular , Células Tumorales Cultivadas , Tamaño de la Partícula
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