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1.
Biomater Sci ; 9(7): 2508-2518, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33459733

RESUMEN

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Sorafenib (sfb) is widely used in clinics for advanced HCC therapy. However, the therapeutic efficacy of sfb is suboptimal due to its poor water solubility, low bioavailability, and side effects. Here, we employed a clinically safe polymer poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) to prepare a nanoparticle (NP)-based sfb formulation (NP-sfb) and tested its antitumor effect in multiple HCC models. NP-sfb could achieve effective drug loading and remain stable under physiological conditions. NP-sfb could be taken up by HepG2, Hepa1-6, and H22 cells and could efficiently inhibit cell proliferation and/or promote cell apoptosis. In vivo studies indicated that NP-sfb showed significantly improved therapeutic efficacy compared with free-sfb at the same dose or even higher doses. Mechanistic studies demonstrated that NP-sfb not only inhibited tumor proliferation and angiogenesis but also stimulated the tumor microenvironment by reducing the infiltration of immunosuppressive myeloid cells and increasing the ratio of cytotoxic T cells. This study demonstrates that the NP-based formulation is a promising strategy to improve the clinical application of sfb.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Antineoplásicos/uso terapéutico , Disponibilidad Biológica , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Polímeros/uso terapéutico , Sorafenib , Microambiente Tumoral
3.
ACS Nano ; 14(3): 3563-3575, 2020 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-32053346

RESUMEN

Polymeric nanoparticles (NPs) are an important category of drug delivery systems, and their in vivo fate is closely associated with delivery efficacy. Analysis of the protein corona on the surface of NPs to understand the in vivo fate of different NPs has been shown to be reliable but complicated and time-consuming. In this work, we establish a simple approach for predicting the in vivo fate of polymeric NPs. We prepared a series of poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-b-PLA) NPs with different protein binding behaviors by adjusting their PEG densities, which were determined by analyzing the serum protein adsorption. We further determined the protein binding affinity, denoted as the equilibrium association constant (KA), to correlate with in vivo fate of NPs. The in vivo fate, including blood clearance and Kupffer cell uptake, was studied, and the maximum concentration (Cmax), the area under the plasma concentration-time curve (AUC), and the mean residence time (MRT) were negatively linearly dependent, while Kupffer cell uptake was positively linearly dependent on KA. Subsequently, we verified the reliability of the approach for in vivo fate prediction using poly(methoxyethyl ethylene phosphate)-block-poly(d,l-lactide) (PEEP-b-PLA) and poly(vinylpyrrolidone)-block-poly(d,l-lactide) (PVP-b-PLA) NPs, and the linear relationship between the KA value and their PK parameters further suggests that the protein binding affinity of polymeric NPs can be a direct indicator of their pharmacokinetics.


Asunto(s)
Proteínas Sanguíneas/química , Nanopartículas/química , Polímeros/farmacocinética , Adsorción , Animales , Inyecciones Intravenosas , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Polímeros/administración & dosificación , Polímeros/química , Unión Proteica , Células RAW 264.7 , Propiedades de Superficie
4.
Biomater Sci ; 7(11): 4698-4707, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31495833

RESUMEN

Rheumatoid arthritis (RA) is a systemic autoimmune disease that can cause irreversible joint deformity. There is still no cure for RA, and current therapeutics, including methotrexate and adalimumab, cause serious off-target effects and systemic immunosuppression, which in turn increases the risk of infection. Bruton's tyrosine kinase (BTK) in macrophages and B cells has been demonstrated to be a promising therapeutic target for RA. However, high doses of BTK inhibitors are required for efficient BTK suppression, which limits their clinical use. Small interfering RNA (siRNA) is promising for the silencing of specific genes and has been used for the treatment of multiple diseases. To deliver siRNA into macrophages and B cells for BTK gene silencing, we employed cationic lipid-assisted PEG-b-PLGA nanoparticles (CLANs) to encapsulate siRNA. We demonstrated that macrophages and B cells were able to efficiently ingest the CLANs both in vitro and in vivo. Thereafter, we encapsulated siRNA targeting BTK (siBTK) into the CLANs, denoted as CLANsiBTK, and demonstrated that CLANsiBTK significantly inhibited BTK expression in macrophages and B cells. In a collagen-induced mouse arthritis model, CLANsiBTK treatment dramatically reduced joint inflammation and other RA symptoms but showed no toxicity, proving that using CLANsiBTK is a promising approach for RA therapy.


Asunto(s)
Agammaglobulinemia Tirosina Quinasa/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Nanopartículas/química , Inhibidores de Proteínas Quinasas/farmacología , ARN Interferente Pequeño/farmacología , Animales , Artritis Reumatoide/metabolismo , Ratones
5.
Biomaterials ; 217: 119302, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31271858

RESUMEN

Organ transplantation is the only effective method to treat end-stage organ failure. However, it is continuously plagued by immune rejection, which is mostly caused by T cell-mediated reactions. Dendritic cells (DCs) are professional antigen-presenting cells, and blocking the costimulatory signaling molecule CD40 in DCs inhibits T cell activation and induces transplant tolerance. In this study, to relieve graft rejection, Cas9 mRNA (mCas9) and a guide RNA targeting the costimulatory molecule CD40 (gCD40) were prepared and encapsulated into poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-b-PLGA)-based cationic lipid-assisted nanoparticles (CLAN), denoted CLANmCas9/gCD40. CLAN effectively delivered mCas9/gCD40 into DCs and disrupted CD40 in DCs at the genomic level both in vitro and in vivo. After intravenous injection into an acute mouse skin transplant model, CLANmCas9/gCD40-mediated CD40 disruption significantly inhibited T cell activation, which reduced graft damage and prolonged graft survival. This work provides a promising strategy for reprogramming DCs with nanoparticles carrying the CRISPR/Cas9 system to abate transplant rejection.


Asunto(s)
Proteína 9 Asociada a CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Células Dendríticas/inmunología , Nanomedicina , Tolerancia al Trasplante/inmunología , Animales , Antígenos CD40/metabolismo , Modelos Animales de Enfermedad , Endocitosis , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Activación de Linfocitos/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , ARN Guía de Kinetoplastida/metabolismo
6.
Biomaterials ; 172: 92-104, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29723758

RESUMEN

Inflammation is closely related to the development of many diseases and is commonly characterized by abnormal infiltration of immune cells, especially neutrophils. The current therapeutics of inflammatory diseases give little attention to direct modulation of these diseases with respect to immune cells. Nanoparticles are applied for efficient drug delivery into the disease-related immune cells, but their performance is significantly affected by their surface properties. In this study, to optimize the properties of nanoparticles for modulating neutrophils-related inflammation, we prepared a library of poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-b-PLGA)-based cationic lipid-assisted nanoparticles (CLANs) with different surface PEG density and surface charge. Optimized CLANs for neutrophils targeting were screened in high-fat diet (HFD)-induced type 2 diabetes (T2D) mice. Then, a CRISPR-Cas9 plasmid expressing a guide RNA (gRNA) targeting neutrophil elastase (NE) was encapsulated into the optimized CLAN and denoted as CLANpCas9/gNE. After intravenous injection, CLANpCas9/gNE successfully disrupted the NE gene of neutrophils and mitigated the insulin resistance of T2D mice via reducing the inflammation in epididymal white adipose tissue (eWAT) and in the liver. This strategy provides an example of abating the inflammatory microenvironment by directly modulating immune cells with nanoparticles carrying genome editing tools.


Asunto(s)
Portadores de Fármacos/química , Inflamación/tratamiento farmacológico , Lípidos/química , Nanopartículas/química , Neutrófilos/metabolismo , Animales , Secuencia de Bases , Sistemas CRISPR-Cas/genética , Microambiente Celular , Diabetes Mellitus Tipo 2/inducido químicamente , Portadores de Fármacos/administración & dosificación , Liberación de Fármacos , Edición Génica/métodos , Regulación de la Expresión Génica/efectos de los fármacos , Terapia Genética/métodos , Resistencia a la Insulina/genética , Masculino , Ratones Endogámicos C57BL , Modelos Animales , Terapia Molecular Dirigida/métodos , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Poliésteres/química , Polietilenglicoles/química
7.
Biomater Sci ; 6(3): 642-650, 2018 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-29412203

RESUMEN

Surface charge plays an important role in determining the interactions of nanoparticles with biological components. Substantial studies have demonstrated that surface charge affects the fate of nanoparticles after intravenous administration; however, few studies have investigated the effect of surface charge on the bioavailability and absorption of nanoparticles after oral administration. In this study, polymeric nanoparticles with a similar particle size and surface polyethylene glycol (PEG) density, but with varying surface charges (positive, negative and neutral), were developed to study the effect of surface charge on the oral absorption of polymeric nanoparticles. The nanoparticles were constructed from polyethylene glycol-block-polylactic acid (PEG-PLA) with the incorporation of lipid components with different charges. Our results suggested that the positive surface charge facilitated the cellular uptake and transport of nanoparticles through both Caco-2 cells in vitro and small intestinal epithelial cells in vivo. The positively charged nanoparticles showed a favorable distribution in the small intestine, and significantly improved the oral bioavailability. This study presents valuable information towards the design of nanoparticles for improved oral drug delivery.


Asunto(s)
Absorción Intestinal , Nanopartículas/metabolismo , Electricidad Estática , Administración Oral , Animales , Células CACO-2 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Nanopartículas/administración & dosificación , Nanopartículas/química , Polietilenglicoles/química , Distribución Tisular
8.
ACS Nano ; 12(2): 994-1005, 2018 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-29314827

RESUMEN

The CRISPR/Cas9 gene editing technology holds promise for the treatment of multiple diseases. However, the inability to perform specific gene editing in targeted tissues and cells, which may cause off-target effects, is one of the critical bottlenecks for therapeutic application of CRISPR/Cas9. Herein, macrophage-specific promoter-driven Cas9 expression plasmids (pM458 and pM330) were constructed and encapsulated in cationic lipid-assisted PEG-b-PLGA nanoparticles (CLAN). The obtained nanoparticles encapsulating the CRISPR/Cas9 plasmids were able to specifically express Cas9 in macrophages as well as their precursor monocytes both in vitro and in vivo. More importantly, after further encoding a guide RNA targeting Ntn1 (sgNtn1) into the plasmid, the resultant CLANpM330/sgNtn1 successfully disrupted the Ntn1 gene in macrophages and their precursor monocytes in vivo, which reduced expression of netrin-1 (encoded by Ntn1) and subsequently improved type 2 diabetes (T2D) symptoms. Meanwhile, the Ntn1 gene was not disrupted in other cells due to specific expression of Cas9 by the CD68 promoter. This strategy provides alternative avenues for specific in vivo gene editing with the CRISPR/Cas9 system.


Asunto(s)
Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Edición Génica , Macrófagos/química , Nanopartículas/química , Netrina-1/genética , Animales , Sistemas CRISPR-Cas/genética , Cationes/química , Células Cultivadas , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/metabolismo , Dieta Alta en Grasa , Células HEK293 , Humanos , Lípidos/química , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Netrina-1/metabolismo , Polímeros/química , Células RAW 264.7
9.
Biomaterials ; 103: 44-55, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27376558

RESUMEN

Cancer stem cells (CSCs) have garnered increasing attention over the past decade, as they are believed to play a crucial role in tumor initiation, progression and metastasis, relapse and drug resistance. Therapeutic strategies which simultaneously exterminate both bulk tumor cells and the rare CSC subpopulation may produce striking response and result in long-term tumor remission. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival of CSCs. The role of autophagy in the susceptibility of breast CSCs to chemotherapeutics was investigated in the present work, reduced 'stemness' and increased susceptibility to chemotherapy drugs (doxorubicin, DOX and docetaxel, DTXL) were observed after chloroquine (CQ)-mediated autophagy inhibition in sorted ALDH(hi) cells of breast cancer cell line MDA-MB-231. We further proved that nanoparticle-mediated autophagy inhibition promoted the efficacy of chemotherapeutics against ALDH(hi) MDA-MB-231 cells in vitro. Administration of drug delivery systems significantly prolonged the circulation half-life and augmented enrichment of two different drugs in tumor tissues and ALDH(hi) cells. More importantly, compared with single treatment, the combined delivery systems NPCQ/NPDOX and NPCQ/DOX (NPCQ/NPDTXL and NPCQ/DTXL) showed most effective and persistent tumor growth inhibitory effect by eliminating bulk tumor cells as well as CSCs (p < 0.01) in an MDA-MB-231 orthotopic tumor murine model. Therefore, our research provides new insights into the nanoparticle-facilitated combination of autophagy inhibition and chemotherapy for effective therapy of breast cancer.


Asunto(s)
Antineoplásicos/administración & dosificación , Autofagia/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Nanopartículas/administración & dosificación , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Animales , Línea Celular Tumoral , Quimioterapia Combinada/métodos , Femenino , Humanos , Ratones , Ratones Endogámicos ICR , Ratones SCID , Resultado del Tratamiento
10.
Proc Natl Acad Sci U S A ; 113(15): 4164-9, 2016 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-27035960

RESUMEN

A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.


Asunto(s)
Antineoplásicos/uso terapéutico , Nanopartículas , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Apoptosis , Línea Celular Tumoral , Humanos , Metástasis de la Neoplasia , Neoplasias/patología , Esferoides Celulares
11.
Biomaterials ; 94: 9-19, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27088406

RESUMEN

Chemotherapy resistance has become a major challenge in the clinical treatment of lung cancer which is the leading cancer type for the estimated deaths. Recent studies have shown that nanoparticles as drug carriers can raise intracellular drug concentration by achieving effectively cellular uptake and rapid drug release, and therefore reverse the acquired chemoresistance of tumors. In this context, nanoparticles-based chemotherapy represents a promising strategy for treating malignancies with chemoresistance. In the present study, we developed cationic lipid assisted nanoparticles (CLAN) to deliver polylactide-cisplatin prodrugs to drug resistant lung cancer cells. The nanoparticles were formulated through self-assembly of a biodegradable poly(ethylene glycol)-block-poly(lactide) (PEG-PLA), a hydrophobic polylactide-cisplatin prodrug, and a cationic lipid. The cationic nanoparticles were proven to significantly improve cell uptake of cisplatin, leading to an increased DNA-Pt adduct and significantly promoted DNA damage in vitro. Moreover, our study reveals that cationic nanoparticles, although are slightly inferior in blood circulation and tumor accumulation, are more effective in blood vessel extravasation. The CLANs ultimately enhances the cellular drug availability and leads to the reversal of cisplatin resistance.


Asunto(s)
Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Lípidos/química , Nanopartículas/química , Profármacos/farmacología , Células A549 , Animales , Cationes , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cisplatino/química , Cisplatino/farmacocinética , Ácidos Grasos Monoinsaturados/química , Femenino , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/ultraestructura , Poliésteres/química , Polietilenglicoles/química , Profármacos/química , Profármacos/farmacocinética , Compuestos de Amonio Cuaternario/química , Distribución Tisular/efectos de los fármacos
12.
Angew Chem Int Ed Engl ; 55(3): 1010-4, 2016 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-26756443

RESUMEN

Successful bench-to-bedside translation of nanomedicine relies heavily on the development of nanocarriers with superior therapeutic efficacy and high biocompatibility. However, the optimal strategy for improving one aspect often conflicts with the other. Herein, we report a tactic of designing tumor-pH-labile linkage-bridged copolymers of clinically validated poly(D,L-lactide) and poly(ethylene glycol) (PEG-Dlink(m)-PDLLA) for safe and effective drug delivery. Upon arriving at the tumor site, PEG-Dlink(m)-PDLLA nanoparticles will lose the PEG layer and increase zeta potential by responding to tumor acidity, which significantly enhances cellular uptake and improves the in vivo tumor inhibition rate to 78.1% in comparison to 47.8% of the non-responsive control. Furthermore, PEG-Dlink(m)-PDLLA nanoparticles show comparable biocompatibility with the clinically used PEG-b-PDLLA micelle. The improved therapeutic efficacy and safety demonstrate great promise for our strategy in future translational studies.


Asunto(s)
Antineoplásicos/uso terapéutico , Concentración de Iones de Hidrógeno , Neoplasias/tratamiento farmacológico , Polímeros/química , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Humanos , Nanopartículas , Neoplasias/química
13.
Biomaterials ; 82: 48-59, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26751819

RESUMEN

Cancer stem cells (CSCs), which hold a high capacity for self-renewal, play a central role in the development, metastasis, and recurrence of various malignancies. CSCs must be eradicated to cure instances of cancer; however, because they can reside far from tumor vessels, they are not easily targeted by drug agents carried by nanoparticle-based drug delivery systems. We herein demonstrate that promoting tumor penetration of nanoparticles by transforming growth factor ß (TGF-ß) signaling pathway inhibition facilitates CSC therapy. In our study, we observed that although nanoparticles carrying siRNA targeting the oncogene polo-like kinase 1 (Plk1) efficiently killed breast CSCs derived from MDA-MB-231 cells in vitro, this intervention enriched CSCs in the residual tumor tissue following systemic treatment. However, inhibition of the TGF-ß signaling pathway with LY364947, an inhibitor of TGF-ß type I receptor, promoted the penetration of nanoparticles in tumor tissue, significantly ameliorating the intratumoral distribution of nanoparticles in MDA-MB-231 xenografts and further leading to enhanced internalization of nanoparticles by CSCs. As a result, synergistic treatment with a nanoparticle drug delivery system and LY364947 inhibited tumor growth and reduced the proportion of CSCs in vivo. This study suggests that enhanced tumor penetration of drug-carrying nanoparticles can enhance CSCs clearance in vivo and consequently provide superior anti-tumor effects.


Asunto(s)
Nanocápsulas/química , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Pirazoles/administración & dosificación , Pirroles/administración & dosificación , ARN Interferente Pequeño/administración & dosificación , Factor de Crecimiento Transformador beta/metabolismo , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Células Madre Neoplásicas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Resultado del Tratamiento
14.
J Am Chem Soc ; 137(48): 15217-24, 2015 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-26571079

RESUMEN

Although surface PEGylation of siRNA vectors is effective for preventing protein adsorption and thereby helps these vectors to evade the reticuloendothelial system (RES) in vivo, it also suppresses the cellular uptake of these vectors by target cells. This dilemma could be overcome by employing stimuli-responsive shell-detachable nanovectors to achieve enhanced cellular internalization while maintaining prolonged blood circulation. Among the possible stimuli, dysregulated pH in tumor (pHe) is the most universal and practical. However, the design of pHe-sensitive system is problematic because of the subtle differences between the pHe and pH in other tissues. Here, a simple acid-sensitive bridged copolymer is developed and used for tumor-targeted systemic delivery of siRNA. After forming the micelleplex delivery system, the corresponding nanoparticles (Dm-NP) might undergo several modifications as follows: (i) a poly(ethylene glycol) (PEG) corona, which is stable in the circulatory system and protects nanovectors from RES clearance; (ii) a pHe responsive linkage breakage, which induces PEG detachment at tumor sites and thereby facilitates cell targeting; and (iii) a cell-penetration peptide, which is exposed upon the removal of PEG and further enhances cellular uptake. Thus, Dm-NP achieved both prolonged circulation and effective accumulation in tumor cells and resulted in the safe and enhanced inhibition of non-small cell lung cancer growth.


Asunto(s)
Neoplasias/metabolismo , Polímeros/química , ARN Interferente Pequeño/administración & dosificación , Micelas , ARN Interferente Pequeño/farmacocinética , Distribución Tisular
15.
Biomaterials ; 37: 405-14, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25453968

RESUMEN

Combination treatment through simultaneous delivery of two or more drugs with nanoparticles has been demonstrated to be an elegant and efficient approach for cancer therapy. Herein, we employ a combination therapy for eliminating both the bulk tumor cells and the rare cancer stem cells (CSCs) that have a high self-renewal capacity and play a critical role in cancer treatment failure. All-trans-retinoic acid (ATRA), a powerful differentiation agent of cancer stem cells and the clinically widely used chemotherapy agent doxorubicin (DOX) are simultaneously encapsulated in the same nanoparticle by a single emulsion method. It is demonstrated that ATRA and DOX simultaneous delivery-based therapy can efficiently deliver the drugs to both non-CSCs and CSCs to differentiate and kill the cancer cells. Differentiation of CSCs into non-CSCs can reduce their self-renewal capacity and increase their sensitivity to chemotherapy; with the combined therapy, a significantly improved anti-cancer effect is demonstrated. Administration of this combinational drug delivery system can markedly augment the enrichment of drugs both in tumor tissues and cancer stem cells, prodigiously enhancing the suppression of tumor growth while reduce the incidence of CSC in a synergistic manner.


Asunto(s)
Doxorrubicina/uso terapéutico , Sistemas de Liberación de Medicamentos , Células Madre Neoplásicas/patología , Tretinoina/uso terapéutico , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/sangre , Doxorrubicina/farmacología , Sinergismo Farmacológico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inyecciones Intravenosas , Ratones Endogámicos NOD , Ratones SCID , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Tamaño de la Partícula , Antígeno Nuclear de Célula en Proliferación/metabolismo , Electricidad Estática , Tretinoina/administración & dosificación , Tretinoina/sangre , Tretinoina/farmacología
16.
Zhonghua Zhong Liu Za Zhi ; 30(3): 237-40, 2008 Mar.
Artículo en Chino | MEDLINE | ID: mdl-18756946

RESUMEN

OBJECTIVE: To evaluate the diagnostic value of multislice spiral CT (MSCT) pneumocolon and image reconstruction in colorectal carcinomas. METHODS: 206 patients with suspected colorectal cancer underwent whole abdominal fast volume scan using 16-slice spiral CT before they were insufflated with 1000-1500 ml air through the anus. Then the axis data were transferred to workstation for imaging by MPR, SSD, Raysum, MIP and CTVE, respectively. The results of MSCT diagnosis were compared with those of surgical pathology and from some other common adjunctive techniques, such as ultrasonography (US), colonoscopy (CC), and etc. RESULTS: In this group, 192 cases were confirmed to be colorectal cancer by surgical pathology. 189 cases were identified by MSCT. The sensitivity, specificity and accuracy was 98.4%, 92.8% and 98.1%, respectively. The accuracy rate of general tumor classification was 98.4%. These data were compared with those by US and CC, Statistical analysis showed that the qualitative diagnosis of MSCT is more accurate than those of other two examination methods, indicating that it is most valuable clinical detection approach at present. CONCLUSION: MSCT pneumocolon is a superior detecting method as it is safe, quick and accurate. Due to the accuracy in orienting and qualitative diagnosis by comprehensive application of 2D and 3D imaging techniques, it can clearly display the detailed information of tumor in terms of morphological characteristics, blood-supply resources and pericolonic lymph nodes involvement, which provides reliable basis for making rational surgical protocol.


Asunto(s)
Neoplasias Colorrectales/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada Espiral/métodos , Adulto , Anciano , Anciano de 80 o más Años , Colonoscopía , Neoplasias Colorrectales/patología , Femenino , Humanos , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Ultrasonografía , Adulto Joven
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