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1.
Int J Nanomedicine ; 16: 1943-1960, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727808

RESUMEN

Introduction: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC. Methods: Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was 99mTc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations. Secondly, nanoparticles were loaded with DOX and their in vitro and ex vivo/in vivo delivery was assessed, in comparison with liposomal Doxorubicin (Caelyx). Finally, the treatment efficacy of DOX-SiNPs-TZ (1:8 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors. Results: SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls. Conclusion: These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Portadores de Fármacos/química , Nanopartículas/química , Radiofármacos/química , Receptor ErbB-2/metabolismo , Dióxido de Silicio/química , Tecnecio/química , Animales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Endocitosis , Femenino , Fluoresceína-5-Isotiocianato/química , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Polietilenglicoles/química , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéutico , Proteoma/metabolismo , Proteómica , Radiofármacos/farmacocinética , Tecnecio/farmacocinética , Distribución Tisular/efectos de los fármacos , Tomografía Computarizada de Emisión de Fotón Único , Resultado del Tratamiento
2.
Int J Nanomedicine ; 16: 1961-1976, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727809

RESUMEN

Introduction: Metastatic breast cancer seriously harms women's health and is currently the tumour type with the highest mortality rate in women. Recently, the combinatorial therapeutic approaches that integrate anti-cancer drugs and genetic agents is an attractive and promising strategy for the treatment of metastatic breast cancer. Moreover, such a combination strategy requires better drug carriers that can effectively deliver the cargo to the breast cancer cells and achieve controlled release in the cells to achieve better therapeutic effects. Methods: The tumour-targeted and redox-responsive mesoporous silica nanoparticles (MSNs) functionalised with DNA aptamers (AS1411) as a co-delivery system was developed and investigated for the potential against metastatic breast cancer. Doxorubicin (Dox) was loaded onto the MSNs, while AS1411 and a small interfering RNA (siTIE2) were employed as gatekeepers via attachment to the MSNs with redox-sensitive disulfide bonds. Results: The controlled release of Dox and siTIE2 was associated with intracellular glutathione. AS1411 mediated the targeted delivery of Dox by increasing its cellular uptake in metastatic breast cancer, ultimately resulting in a lower IC50 in MDA-MB-231 cells (human breast cancer cell line with high metastatic potency), improved biodistribution in tumour-bearing mice, and enhanced in vivo anti-tumour effects. The in vitro cell migration/invasion assay and in vivo anti-metastatic study revealed synergism in the co-delivery system that suppresses cancer cell metastasis. Conclusion: The tumour-targeted and redox-responsive MSN prepared in this study are promising for the effective delivery and controlled release of Dox and siTIE2 for improved treatment of metastatic breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Nanopartículas/química , ARN Interferente Pequeño/administración & dosificación , Dióxido de Silicio/química , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/patología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada/farmacología , Preparaciones de Acción Retardada/uso terapéutico , Doxorrubicina/farmacología , Portadores de Fármacos/química , Endocitosis/efectos de los fármacos , Femenino , Células HEK293 , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/ultraestructura , Invasividad Neoplásica , Metástasis de la Neoplasia , Oxidación-Reducción , Porosidad , ARN Interferente Pequeño/farmacología , Distribución Tisular/efectos de los fármacos
3.
AAPS PharmSciTech ; 22(3): 94, 2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33683493

RESUMEN

Hydrochlorothiazide (HTZ) is a first-line drug used in the treatment of hypertension suffered from low oral bioavailability due to poor aqueous solubility and permeability. Hence, lyophilized egg white protein-based solid dispersion (HTZ-EWP SD) was developed to explore its feasibility as a solid dispersion carrier for enhanced aqueous solubility and permeability of HTZ. The HTZ-EWP SD was prepared using the kneading method. HTZ-EWP SD was characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectroscopy (FT-IR), powder X-ray diffractometer (PXRD), solubility, in vitro dissolution, and ex vivo permeation studies. The physico-chemical evaluation suggested the formation of the solid dispersion. Optimized HTZ-EWP SD4 drastically enhanced (~32-fold) aqueous solubility (~16.12 ± 0.08 mg/mL) over to pure HTZ (~ 0.51 ± 0.03 mg/mL). The dissolution study in phosphate buffer media (pH 6.8) revealed that HTZ-EWP SD4 significantly enhanced the release rate of HTZ (~ 87 %) over to HTZ (~ 25 %). The permeation rate of HTZ from optimized HTZ-EWP SD4 was enhanced significantly (~ 84 %) compared to pure HTZ (~ 24 %). Optimized HTZ-EWP-SD4 enhanced the rate of HTZ dissolution (~ 86 %) in FeSSIF (fed state simulated intestinal fluid), compared to a low dissolution rate (~ 72 %) in FaSSIF (fasted state simulated intestinal fluid) state after 2-h study. Obtained results conclude that lyophilized egg white protein can be utilized as an alternative solid dispersion carrier for enhancing the solubility and permeability of HTZ.


Asunto(s)
Diuréticos/administración & dosificación , Diuréticos/química , Portadores de Fármacos/química , Proteínas del Huevo/química , Hidroclorotiazida/administración & dosificación , Hidroclorotiazida/química , Disponibilidad Biológica , Tampones (Química) , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Permeabilidad , Solubilidad , Agua
4.
Int J Nanomedicine ; 16: 1617-1630, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33688182

RESUMEN

Introduction: The clinical use of the antitumoral drug doxorubicin (Dox) is reduced by its dose-limiting toxicity, related to cardiotoxic side effects and myelosuppression. In order to overcome these drawbacks, here we describe the synthesis, the structural characterization and the in vitro cytotoxicity assays of hydrogels (HGs) and nanogels (NGs) based on short peptide sequences loaded with Dox or with its liposomal formulation, Doxil. Methods: Fmoc-FF alone or in combination with (FY)3 or PEG8-(FY)3 peptides, at two different ratios (1/1 and 2/1 v/v), were used for HGs and NGs formulations. HGs were prepared according to the "solvent-switch" method, whereas NGs were obtained through HG submicronition by the top-down methodology in presence of TWEEN®60 and SPAN®60 as stabilizing agents. HGs gelation kinetics were assessed by Circular Dichroism (CD). Stability and size of NGs were studied using Dynamic Light Scattering (DLS) measurements. Cell viability of empty and filled Dox HGs and NGs was evaluated on MDA-MB-231 breast cancer cells. Moreover, cell internalization of the drug was evaluated using immunofluorescence assays. Results: Dox filled hydrogels exhibit a high drug loading content (DLC=0.440), without syneresis after 10 days. Gelation kinetics (20-40 min) and the drug release (16-28%) over time of HGs were found dependent on relative peptide composition. Dox filled NGs exhibit a DLC of 0.137 and a low drug release (20-40%) after 72 h. Empty HGs and NGs show a high cell viability (>95%), whereas Dox loaded ones significantly reduce cell viability after 24 h (49-57%) and 72 h (7-25%) of incubation, respectively. Immunofluorescence assays evidenced a different cell localization for Dox delivered through HGs and NGs with respect to the free drug. Discussion: A modulation of the Dox release can be obtained by changing the ratios of the peptide components. The different cellular localization of the drug loaded into HGs and NGs suggests an alternative internalization mechanism. The high DLC, the low drug release and preliminary in vitro results suggest a potential employment of peptide-based HGs and NGs as drug delivery tools.


Asunto(s)
Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos , Hidrogeles/química , Nanogeles/química , Péptidos/química , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacología , Portadores de Fármacos/química , Liberación de Fármacos , Dispersión Dinámica de Luz , Endocitosis/efectos de los fármacos , Humanos
5.
Int J Nanomedicine ; 16: 1681-1706, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33688185

RESUMEN

The unique properties of carbon nanotubes (CNTs) (such as their high surface to volume ratios, enhanced conductivity and strength, biocompatibility, ease of functionalization, optical properties, etc.) have led to their consideration to serve as novel drug and gene delivery carriers. CNTs are effectively taken up by many different cell types through several mechanisms. CNTs have acted as carriers of anticancer molecules (including docetaxel (DTX), doxorubicin (DOX), methotrexate (MTX), paclitaxel (PTX), and gemcitabine (GEM)), anti-inflammatory drugs, osteogenic dexamethasone (DEX) steroids, etc. In addition, the unique optical properties of CNTs have led to their use in a number of platforms for improved photo-therapy. Further, the easy surface functionalization of CNTs has prompted their use to deliver different genes, such as plasmid DNA (PDNA), micro-RNA (miRNA), and small interfering RNA (siRNA) as gene delivery vectors for various diseases such as cancers. However, despite all of these promises, the most important continuous concerns raised by scientists reside in CNT nanotoxicology and the environmental effects of CNTs, mostly because of their non-biodegradable state. Despite a lack of widespread FDA approval, CNTs have been studied for decades and plenty of in vivo and in vitro reports have been published, which are reviewed here. Lastly, this review covers the future research necessary for the field of CNT medicine to grow even further.


Asunto(s)
Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Nanotubos de Carbono/química , Endocitosis , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/terapia
6.
Int J Nanomedicine ; 16: 1775-1787, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33692622

RESUMEN

Purpose: To avoid undefined metabolic mechanisms and to eliminate potential side effects of traditional nanocarriers, new green carriers are urgently needed in cancer treatment. Carrier-free nanoparticles (NPs) based on ursolic acid (UA) have attracted significant attention, but the UA NPs targeting the folate receptor have never been explored. We designed a novel self-assembled UA-Methotrexate (MTX) NPs targeting the folate-receptor and its synergetic anticancer activity was studied in vitro and in vivo. Methods: UA-MTX NPs were prepared using the solvent precipitation method. Characterization of the UA-MTX NPs preparation was performed using a size analyzer, transmission electron microscopy, and UV-vis spectrophotometry. The in vitro pH-responsive drug release capability of UA-MTX NPs was tested at different pH values. The UA-MTX NPs targeting of folates was determined by comparing the endocytosis rates of cell lines with low or overexpression of the folate receptor (A549 and MCF-7 cells). The cytotoxicity and cell apoptosis of UA-MTX NPs were also studied to determine the in vitro synergistic effects. Combination chemotherapy of UA-MTX NPs in vivo was evaluated using MCF-7 xenografted tumor models. Results: Compared with free UA or MTX, the water solubility of UA-MTX NPs improved significantly. Drug-release from the UA-MTX NPs was faster at pH 5.0 than pH 7.4, suggesting MTX-UA NPs could rapidly release MTX in the acidic conditions of the tumor microenvironment. Confocal laser scanning microscopy revealed the excellent folate receptor targeting of UA-MTX NPs in MCF-7 cells. Cytotoxicity and cell apoptosis results demonstrated greater antiproliferative capacity of UA-MTX NPs than that of free drug in folate receptor overexpressing MCF-7 cells. Anticancer effects in vivo suggested MTX-UA NPs exhibited good biological safety and could enhance antitumor efficacy due to the combination therapy. Conclusion: Our findings indicate that the UA-MTX NPs targeting folate-receptors is an efficient strategy for combination chemotherapy.


Asunto(s)
Antineoplásicos/farmacología , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Receptores de Folato Anclados a GPI/metabolismo , Metotrexato/farmacología , Nanopartículas/química , Triterpenos/farmacología , Animales , Antineoplásicos/administración & dosificación , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Sinergismo Farmacológico , Endocitosis/efectos de los fármacos , Femenino , Ácido Fólico/química , Humanos , Células MCF-7 , Metotrexato/administración & dosificación , Metotrexato/química , Ratones Desnudos , Nanopartículas/ultraestructura , Ratas Wistar , Triterpenos/administración & dosificación , Triterpenos/química
7.
Int J Nanomedicine ; 16: 1837-1847, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33692624

RESUMEN

Introduction: Nanotube-based drug delivery systems have received considerable attention because of their large internal volume to encapsulate the drug and the ability to penetrate tissues, cells, and bacteria. In this regard, understanding the interaction between the drug and the nanotube to evaluate the encapsulation behavior of the drug in the nanotube is of crucial importance. Methods: In this work, the encapsulation process of the cationic antimicrobial peptide named cRW3 in the biocompatible boron nitride nanotube (BNNT) was investigated under the Canonical ensemble (NVT) by molecular dynamics (MD) simulation. Results: The peptide was absorbed into the BNNT by van der Waals (vdW) interaction between cRW3 and the BNNT, in which the vdW interaction decreased during the simulation process and reached the value of -142.7 kcal·mol-1 at 4 ns. Discussion: The increase in the potential mean force profile of the encapsulated peptide during the pulling process of cRW3 out of the nanotube showed that its insertion into the BNNT occurred spontaneously and that the inserted peptide had the desired stability. The energy barrier at the entrance of the BNNT caused a pause of 0.45 ns when half of the peptide was inside the BNNT during the encapsulation process. Therefore, during this period, the peptide experienced the weakest movement and the smallest conformational changes.


Asunto(s)
Compuestos de Boro/química , Portadores de Fármacos/química , Nanotubos/química , Proteínas Citotóxicas Formadoras de Poros/farmacología , Aminoácidos/química , Sistemas de Liberación de Medicamentos , Simulación de Dinámica Molecular , Proteínas Citotóxicas Formadoras de Poros/química , Conformación Proteica , Termodinámica
8.
Int J Nanomedicine ; 16: 2123-2136, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33731994

RESUMEN

Purpose: Nanomaterial-based drug-delivery systems allowing for effective targeted delivery of smallmolecule chemodrugs to tumors have revolutionized cancer therapy. Recently, as novel nanomaterials with outstanding physicochemical properties, boron nitride nanospheres (BNs) have emerged as a promising candidate for drug delivery. However, poor dispersity and lack of tumor targeting severely limit further applications. In this study, cancer cell-membrane biomimetic BNs were designed for targeted anticancer drug delivery. Methods: Cell membrane extracted from HeLa cells (HM) was used to encapsulate BNs by physical extrusion. Doxorubicin (Dox) was loaded onto HM-BNs as a model drug. Results: The cell-membrane coating endowed the BNs with excellent dispersibility and cytocompatibility. The drug-release profile showed that the Dox@HM-BNs responded to acid pH, resulting in rapid Dox release. Enhanced cellular uptake of Dox@HM-BNs by HeLa cells was revealed because of the homologous targeting of cancer-cell membranes. CCK8 and live/dead assays showed that Dox@HM-BNs had stronger cytotoxicity against HeLa cells, due to self-selective cellular uptake. Finally, antitumor investigation using the HeLa tumor model demonstrated that Dox@HM-BNs possessed much more efficient tumor inhibition than free Dox or Dox@BNs. Conclusion: These findings indicate that the newly developed HM-BNs are promising as an efficient tumor-selective drug-delivery vehicle for tumor therapy.


Asunto(s)
Materiales Biomiméticos/química , Compuestos de Boro/química , Membrana Celular/patología , Terapia Molecular Dirigida , Nanosferas/química , Neoplasias/patología , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Peso Corporal/efectos de los fármacos , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Femenino , Células HEK293 , Humanos , Ratones Endogámicos BALB C , Nanosferas/ultraestructura , Neoplasias/tratamiento farmacológico , Espectrometría por Rayos X , Distribución Tisular/efectos de los fármacos
9.
ACS Appl Mater Interfaces ; 13(6): 7102-7114, 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33528239

RESUMEN

Overproduction of reactive oxygen species (ROS) and inflammation are two key pathogeneses of noise-induced hearing loss (NIHL), which leads to outer hair cell (OHC) damage and hearing loss. In this work, we successfully developed ROS-responsive nanoparticles as berberine (BBR) carriers (PL-PPS/BBR) for OHC-targeted therapy of NIHL: Prestin-targeting peptide 2 (PrTP2)-modified nanoparticles (PL-PPS/BBR), which effectively accumulated in OHC areas, and poly(propylene sulfide)120 (PPS120), which scavenged ROS and converted to poly(propylene sulfoxide)120 in a ROS environment to disintegrate and provoke the rapid release of BBR with anti-inflammatory and antioxidant effects. In this study, satisfactory anti-inflammatory and antioxidant effects of PL-PPS/BBR were confirmed. Immunofluorescence and scanning electron microscopy (SEM) images showed that PL-PPS/BBR effectively accumulated in OHCs and protected the morphological integrity of OHCs. The auditory brainstem response (ABR) results demonstrated that PL-PPS/BBR significantly improved hearing in NIHL guinea pigs after noise exposure. This work suggested that PL-PPS/BBR may be a new potential treatment for noise-associated injury with clinical application.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Berberina/farmacología , Células Ciliadas Auditivas Externas/efectos de los fármacos , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Especies Reactivas de Oxígeno/química , Animales , Antiinflamatorios no Esteroideos/química , Antioxidantes/química , Berberina/química , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Cobayas , Estructura Molecular , Nanopartículas/química , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismo , Propiedades de Superficie
10.
Int J Nanomedicine ; 16: 925-939, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33603360

RESUMEN

Background: Antimicrobial resistance poses substantial risks to human health. Thus, there is an urgent need for novel antimicrobial agents, including alternative compounds, such as peptides derived from bacterial toxin-antitoxin (TA) systems. ParELC3 is a synthetic peptide derived from the ParE toxin reported to be a good inhibitor of bacterial topoisomerases and is therefore a potential antibacterial agent. However, ParELC3 is inactive against bacteria due to its inability to cross the bacterial membranes. To circumvent this limitation we prepared and used rhamnolipid-based liposomes to carry and facilitate the passage of ParELC3 through the bacterial membrane to reach its intracellular target - the topoisomerases. Methods and Results: Small unilamellar liposome vesicles were prepared by sonication from three formulations that included 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and cholesterol. ParELC3 was loaded with high efficiency into the liposomes. Characterization by DLS and TEM revealed the appropriate size, zeta potential, polydispersity index, and morphology. In vitro microbiological experiments showed that ParELC3 loaded-liposomes are more efficient (29 to 11 µmol·L-1) compared to the free peptide (>100 µmol·L-1) at inhibiting the growth of standard E. coli and S. aureus strains. RL liposomes showed high hemolytic activity but when prepared with POPC and Chol this activity had a significant reduction. Independently of the formulation, the vesicles had no detectable cytotoxicity to HepG2 cells, even at the highest concentrations tested (1.3 mmol·L-1 and 50 µmol·L-1 for rhamnolipid and ParELC3, respectively). Conclusion: The present findings suggest the potential use of rhamnolipid-based liposomes as nanocarrier systems to enhance the bioactivity of peptides.


Asunto(s)
Antibacterianos/farmacología , Portadores de Fármacos/química , Glucolípidos/química , Nanopartículas/química , Péptidos/farmacología , Sistemas Toxina-Antitoxina , Secuencia de Aminoácidos , Permeabilidad de la Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Dispersión Dinámica de Luz , Escherichia coli/efectos de los fármacos , Hemólisis/efectos de los fármacos , Células Hep G2 , Humanos , Hidrodinámica , Liposomas , Pruebas de Sensibilidad Microbiana , Péptidos/química , Sonicación , Staphylococcus aureus/efectos de los fármacos
11.
Int J Nanomedicine ; 16: 1313-1330, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33628022

RESUMEN

Nanotechnology has been actively integrated as drug carriers over the last few years to treat various cancers. The main hurdle in the clinical management of cancer is the development of multidrug resistance against chemotherapeutic agents. To overcome the limitations of chemotherapy, the researchers have been developing technological advances for significant progress in the oncotherapy by enabling the delivery of chemotherapeutic agents at increased drug content levels to the targeted spots. Several nano-drug delivery systems designed for tumor-targeting are evaluated in preclinical and clinical trials and showed promising outcomes in cancerous tumors' clinical management. This review describes nanocarrier's importance in managing different types of cancers and emphasizing nanocarriers for drug delivery and cancer nanotherapeutics. It also highlights the recent advances in nanocarriers-based delivery systems, including polymeric nanocarriers, micelles, nanotubes, dendrimers, magnetic nanoparticles, solid lipid nanoparticles, and quantum dots (QDs). The nanocarrier-based composites are discussed in terms of their structure, characteristics, and therapeutic applications in oncology. To conclude, the challenges and future exploration opportunities of nanocarriers in chemotherapeutics are also presented.


Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Animales , Antineoplásicos/química , Humanos , Lípidos/química , Neoplasias/tratamiento farmacológico , Puntos Cuánticos/química
12.
ACS Appl Mater Interfaces ; 13(7): 8015-8025, 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33561348

RESUMEN

Deoxyribozyme (DNAzyme) is regarded as a promising gene therapy drug. However, poor cellular uptake efficacy and low biological stability limit the utilization of DNAzyme in gene therapy. Here, we report a well-known programmable DNAzyme-based nanotweezer (DZNT) that provides a new strategy for the detection of TK1 mRNA and survivin mRNA-targeted gene silencing therapy. At the end of the DZNT arm, there are two functionalized single-stranded DNA and each consists of two parts: the segment complementary to TK1 mRNA and the split-DNAzyme segment. The hybridization with intracellular TK1 mRNA enables the imaging of TK1 mRNA. Meanwhile, the hybridization draws the split-DNAzyme close to each other and activates DNAzyme to cleave the survivin mRNA to realize gene silencing therapy. The results demonstrate that the DZNT nanocarrier has excellent cell penetration, good biocompatibility, and noncytotoxicity. DZNT can image intracellular biomolecule TK1 mRNA with a high contrast. Furthermore, the split-DNAzyme can efficiently cleave the survivin mRNA with the aid of TK1 mRNA commonly present in cancer cells, accordingly can selectively kill cancer cells, and has no harm to normal cells. Taken together, the multifunctional programmable DZNT provides a promising platform for the early diagnosis of tumors and gene therapy.


Asunto(s)
Materiales Biocompatibles/metabolismo , ADN Catalítico/metabolismo , Terapia Genética , Nanotecnología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Apoptosis/genética , Materiales Biocompatibles/química , ADN Catalítico/química , Portadores de Fármacos/química , Silenciador del Gen/efectos de los fármacos , Humanos , Tamaño de la Partícula , ARN Mensajero/análisis , Propiedades de Superficie , Células Tumorales Cultivadas
13.
Int J Nanomedicine ; 16: 1051-1066, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33603368

RESUMEN

Background: This study was aimed to prepare a novel magnetic thermosensitive cationic liposome drug carrier for the codelivery of Oxaliplatin (OXA) and antisense lncRNA of MDC1 (MDC1-AS) to Cervical cancer cells and evaluate the efficiency of this drug carrier and its antitumor effects on Cervical cancer. Methods: Thermosensitive magnetic cationic liposomes were prepared using thin-film hydration method. The OXA and MDC1-AS vectors were loaded into the codelivery system, and the in vitro OXA thermosensitive release activity, efficiency of MDC1-AS regulating MDC1, in vitro cytotoxicity, and in vivo antitumor activity were determined. Results: The codelivery system had desirable targeted delivery efficacy, OXA thermosensitive release, and MDC1-AS regulating MDC1. Codelivery of OXA and MDC1-AS enhanced the inhibition of cervical cancer cell growth in vitro and in vivo, compared with single drug delivery. Conclusion: The novel codelivery of OXA and MDC1-AS magnetic thermosensitive cationic liposome drug carrier can be applied in the combined chemotherapy and gene therapy for cervical cancer.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas de Ciclo Celular/genética , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Fenómenos Magnéticos , Terapia Molecular Dirigida , Oxaliplatino/uso terapéutico , ARN Largo no Codificante/administración & dosificación , Neoplasias del Cuello Uterino/terapia , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Cationes , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Liberación de Fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Liposomas , Ratones Endogámicos BALB C , Ratones Desnudos , Oxaliplatino/farmacología , Tamaño de la Partícula , Electricidad Estática , Temperatura , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología
14.
Int J Mol Sci ; 22(4)2021 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-33572073

RESUMEN

The purpose of the study was to obtain an external coating based on nanoparticles of ZnO, carvacrol, and geraniol that could be active against viruses such as SARS-Co-V2. Additionally, the synergistic effect of the chosen substances in coatings was analyzed. The goal of the study was to measure the possible antibacterial activity of the coatings obtained. Testing antiviral activity with human pathogen viruses, such as SARS-Co-V2, requires immense safety measures. Bacteriophages such as phi 6 phage represent good surrogates for the study of airborne viruses. The results of the study indicated that the ZC1 and ZG1 coatings containing an increased amount of geraniol or carvacrol and a very small amount of nanoZnO were found to be active against Gram-positive and Gram-negative bacteria. It is also important that a synergistic effect between these active substances was noted. This explains why polyethylene (PE) films covered with the ZC1 or ZG1 coatings (as internal coatings) were found to be the best packaging materials to extend the quality and freshness of food products. The same coatings may be used as the external coatings with antiviral properties. The ZC1 and ZG1 coatings showed moderate activity against the phi 6 phage that has been selected as a surrogate for viruses such as coronaviruses. It can be assumed that coatings ZG1 and ZC1 will also be active against SARS-CoV-2 that is transmitted via respiratory droplets.


Asunto(s)
Monoterpenos Acíclicos/química , Antibacterianos/química , Antivirales/química , Cimenos/química , Nanopartículas del Metal/química , Óxido de Zinc/química , Antibacterianos/farmacología , Antivirales/farmacología , Bacteriófagos/efectos de los fármacos , /virología , Portadores de Fármacos/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas , /aislamiento & purificación
15.
J Chromatogr A ; 1641: 461959, 2021 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-33611111

RESUMEN

Fluorescent probes are used in drug nanocarrier pre-clinical studies or as active compounds in theranostics and photodynamic therapy. In the biological medium, nanoparticles interact with proteins, which can result in the off-target release of their cargo. The present study used asymmetric flow field-flow fractionation with online multi-angle laser light scattering and fluorescence detection (AF4-MALLS-FLD) to study the release, transfer, and partition of fluorescent dyes from polymeric nanoparticles (NP). NP formulations containing the dyes Rose Bengal, Rhodamine B, DiI, 3-(α-azidoacetyl)coumarin and its polymer conjugate, Nile Red, and IR780 and its polymer conjugate were prepared. NP suspensions were incubated in a medium with serum proteins and then analyzed by AF4. AF4 allowed efficient separation of proteins (< 10 nm) from fluorescently labeled NP (range of 54 - 180 nm in diameters). The AF4 analyses showed that some dyes, such as Rose Bengal, IR780, and Coumarin were transferred to a high extent (68-77%) from NP to proteins. By contrast, for DiI and dye-polymer conjugates, transfer occured to a lower extent. The studies of dye release kinetics showed that the transfer of IR780 from NP to proteins occurs at a high extent (~50%) and rate, while Nile Red was slowly released from the NP over time with reduced association with proteins (~20%). This experiment assesses the stability of fluorescence labeling of nanocarriers and probes the transfer of fluorescent dyes from NP to proteins, which is otherwise not accessible with commonly used techniques of separation, such as dialysis and ultrafiltration/centrifugation employed in drug encapsulation and release studies of nanocarriers. Determining the interaction and transfer of dyes to proteins is of utmost importance in the pre-clinical evaluation of drug nanocarriers for improved correlation between in vitro and in vivo studies.


Asunto(s)
Proteínas Sanguíneas/análisis , Portadores de Fármacos/química , Colorantes Fluorescentes/química , Fraccionamiento de Campo-Flujo/métodos , Nanopartículas/química , Polímeros/química , Adsorción , Fluorescencia , Humanos , Hidrodinámica , Cinética , Oxazinas/química , Teoría Cuántica , Rodaminas/química , Dispersión de Radiación
16.
Int J Nanomedicine ; 16: 609-621, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33531804

RESUMEN

Objective: The aim of the current study was to load fenticonazole nitrate, a slightly water-soluble antifungal agent, into terpene-enriched phospholipid vesicles (terpesomes) as a potential delivery system for the management of ocular fungal infection. Methods: Thin film hydration method was used to prepare terpesomes according to a 32 full factorial design to inspect the effect of several variables on vesicles' features. The investigated factors were terpenes type (X1) and terpenes amount (X2) while the dependent responses were encapsulation efficiency percent (Y1), particle size (Y2) and polydispersity index (Y3). Design Expert® program was used to chose the best achieved formula. The selected terpesomes were further optimized via incorporation of a positive charge inducer (stearylamine) to enhance adhesion to the negatively charged mucus covering the eye surface. The in vivo performance of the optimized fenticonazole nitrate-loaded terpesomes relative to drug suspension was evaluated by measuring the antifungal activity (against Candida albicans) retained in the tear's fluid at different time intervals after ocular application in albino rabbits. Results: The optimized terpesomes showed spherical vesicles with entrapment efficiency of 79.02±2.35%, particle size of 287.25±9.55 nm, polydispersity index of 0.46±0.01 and zeta potential of 36.15±1.06 mV. The in vivo study demonstrated significantly higher ocular retention of the optimized fenticonazole nitrate-loaded terpesomes relative to the drug suspension. Moreover, the histopathological studies proved the safety and biocompatibility of the prepared terpesomes. Conclusion: The obtained results verified the potential of the terpesomes for safe and effective ocular delivery of fenticonazole nitrate.


Asunto(s)
Sistemas de Liberación de Medicamentos , Ojo/efectos de los fármacos , Imidazoles/administración & dosificación , Terpenos/farmacología , Administración Cutánea , Animales , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Portadores de Fármacos/química , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Masculino , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Conejos , Suspensiones
17.
Int J Nanomedicine ; 16: 701-714, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33536755

RESUMEN

Atherosclerosis (AS) as the leading cause of cardiovascular and cerebrovascular events has been paid much attention all the time. With the continuous development of modern medical drug treatment, surgical treatment, interventional treatment and other methods, the mortality rate of AS has shown a downward trend, while the morbidity rate is still increasing. Oral lipid-lowering or anti-inflammatory drugs are generally used for early AS, but the relatively low accumulation efficiency in lesions and the unavoidable side effects required researchers to develop more effective drug delivery approaches for the therapy of AS. Mesoporous silica nanoparticles as nanocarrier for drug delivery have received extensive attentions due to their flexible size, high specific surface area, controlled pore volume, high drug loading capacity and excellent biocompatibility. Series of good reviews about the mesoporous silica nanoparticles loaded drugs for cancer therapy have been well documented. However, their roles as nanocarrier for drug delivery to treat AS have few reports. In this review, the applications and challenges of mesoporous silica nanomaterials in the field of the diagnosis and therapy of AS have been summarized. The classification, synthesis, formation mechanism, surface modification and functionalization of mesoporous silica nanomaterials which were closely related to the theranostic effect of AS have also been included. Last but not the least, the future prospects' suggestions of mesoporous silica nanomaterial-based drug delivery system for AS are also provided.


Asunto(s)
Aterosclerosis/terapia , Nanoestructuras/uso terapéutico , Dióxido de Silicio/uso terapéutico , Aterosclerosis/diagnóstico , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Humanos , Porosidad
18.
Int J Mol Sci ; 22(2)2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33440880

RESUMEN

Osteoarthritis (OA) remains one of the common degenerative joint diseases and a major cause of pain and disability in older adult individuals. Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) (such as diclofenac, DIC) or intra-articular injected gluco-corticosteroids (such as dexamethasone, DEX) were the conventional treatment strategies for OA to reduce joint pain. Current limitations for both drugs including severe adverse effects with risks of toxicity were noted. The aim of the present study was to generate a novel OA treatment formulation hyaluronic acid (HA)-Liposomal (Lipo)-DIC/DEX to combat joint pain. The formulation was prepared by constructing DIC with DEX-loaded nanostructured lipid carriers Lipo-DIC/DEX mixed with hyaluronic acid (HA) for prolonged OA application. The prepared Lipo-DIC/DEX nanoparticles revealed the size as 103.6 ± 0.3 nm on average, zeta potential as -22.3 ± 4.6 mV, the entrapment efficiency of 90.5 ± 5.6%, and the DIC and DEX content was 22.5 ± 4.1 and 2.5 ± 0.6%, respectively. Evidence indicated that HA-Lipo-DIC/DEX could reach the effective working concentration in 4 h and sustained the drug-releasing time for at least 168 h. No significant toxicities but increased cell numbers were observed when HA-Lipo-DIC/DEX co-cultured with articular chondrocytes cells. Using live-animal In vivo imaging system (IVIS), intra-articular injection of each HA-Lipo-DIC/DEX sufficed to reduce knee joint inflammation in OA mice over a time span of four weeks. Single-dose injection could reduce the inflammation volume down to 77.5 ± 5.1% from initial over that time span. Our results provided the novel drug-releasing formulation with safety and efficiency which could be a promising system for osteoarthritis pain control.


Asunto(s)
Dexametasona/administración & dosificación , Diclofenaco/química , Ácido Hialurónico/química , Liposomas , Nanopartículas/química , Animales , Portadores de Fármacos/química , Liberación de Fármacos , Humanos , Cinética , Elastasa de Leucocito/metabolismo , Ratones , Estructura Molecular , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo
19.
ACS Appl Mater Interfaces ; 13(5): 6034-6042, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33499584

RESUMEN

MicroRNA (miRNA) represents a promising class of therapeutic nucleic acid drugs, while delivery challenges remain that impede the advancement of miRNA therapy, largely because of in vivo instability and low delivery efficiency. Herein, we discover the dual roles of metal-organic framework (MOF) nanoparticles (ZIF-8) as nanocarriers for miRNA delivery and adjuvants for chemodynamic therapy. The miR-34a-m@ZIF-8 complex demonstrated efficient cellular uptake and lysosomal stimuli-responsive miRNA release. Zn2+ triggered the generation of reactive oxygen species, which consequently induced apoptosis of tumor cells. Released miR-34a-m led to a remarkable decrease in expression of Bcl-2 at both mRNA and protein levels and enhanced cancer cell apoptosis. In vivo experiments showed high efficacy of using miR-34a-m@ZIF-8 to suppress tumor growth via synergistic gene/chemodynamic therapy in a mouse model of triple-negative breast cancer. Our work demonstrates MOFs as a promising nanoplatform for efficient synergetic gene/chemodynamic therapy.


Asunto(s)
Adyuvantes Farmacéuticos/farmacología , Antibióticos Antineoplásicos/farmacología , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Estructuras Metalorgánicas/química , MicroARNs/farmacología , Nanopartículas/química , Adyuvantes Farmacéuticos/química , Animales , Antibióticos Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Portadores de Fármacos/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Mamarias Experimentales/diagnóstico por imagen , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/metabolismo , Ratones , MicroARNs/química , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismo , Propiedades de Superficie , Zeolitas/química , Zeolitas/farmacología
20.
ACS Appl Mater Interfaces ; 13(5): 5975-5988, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33502166

RESUMEN

The structural layers around oocytes make it difficult to deliver drugs aimed at treating infertility. In this study, we sought to identify nanoparticles (NPs) that could easily pass through zona pellucida (ZP), a special layer around oocytes, for use as a drug delivery carrier. Three types of NPs were tested: quantum dot NPs, PE-polyethylene glycol (PEG)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs (PEG/PL), and tetramethylrhodamine-loaded PLGA NPs (TRNPs). When mouse oocytes were treated with NPs, only TRNPs could fully pass through the ZP and cell membrane. To assess the effects of TRNPs on fertility and potential nanotoxicity, we performed mRNA sequencing analysis to confirm their genetic safety. We established a system to successfully internalize TRNPs into oocytes. The genetic stability and normal development of TRNP-treated oocytes and embryos were confirmed. These results imply that TRNPs can be used as a drug delivery carrier applicable to germ cells.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas/química , Oocitos/efectos de los fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Rodaminas/química , Animales , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Estructura Molecular , Tamaño de la Partícula , Polietilenglicoles/química , Rodaminas/farmacología , Propiedades de Superficie
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