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1.
Mol Pharm ; 18(3): 1327-1343, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33530691

RESUMEN

Single chemotherapy often causes severe adverse effects and drug resistance to limit therapeutic efficacy. As a noninvasive approach, photothermal therapy (PTT) represents an attractive option for cancer therapy due to the benefits of remote control and precise treatment methods. Nanomedicines constructed with combined chemo-photothermal properties may exert synergistic effects and improved antitumor efficacy. In this study, we developed polydopamine (PDA)-coated nanoparticles grafted with folic acid (FA) and polyethylene glycol to transport doxorubicin (DOX) for targeted cancer therapy. The results showed that this delivery vehicle has a nanoscale particle size and narrow size distribution. No particle aggregation or significant drug leakage was observed during the stability test. This system presented excellent photothermal conversion capability under near-infrared light (NIR) laser irradiation due to the PDA layer covering. In vitro dissolution profiles demonstrated that sequential and triggered DOX release from nanoparticles was pH-, NIR irradiation-, and redox level-dependent and could be best fitted with the Ritger-Peppas equation. FA modification effectively promoted the intracellular uptake of nanoparticles by HepG2 cells and therefore significantly inhibited cell recovery and induced tumor cell apoptosis. Compared to the free DOX group, nanoparticles reduced the DOX concentration in the heart to avoid drug-related cardiotoxicity. More importantly, the in vivo antitumor efficacy results showed that compared with the single chemotherapy strategy, the nanoparticle group exerted combined and satisfactory tumor growth inhibition effects with good biocompatibility. In summary, this nanocarrier delivery system can organically combine chemotherapy and PTT to achieve effective and precise cancer treatment.


Asunto(s)
Doxorrubicina/farmacología , Liberación de Fármacos/efectos de los fármacos , Indoles/química , Indoles/farmacología , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Polímeros/química , Polímeros/farmacología , Animales , Doxorrubicina/química , Ácido Fólico/química , Células Hep G2 , Humanos , Hipertermia Inducida/métodos , Rayos Infrarrojos , Masculino , Ratones , Tamaño de la Partícula , Fototerapia/métodos , Terapia Fototérmica/métodos , Polietilenglicoles/química , Ratas , Ratas Sprague-Dawley
2.
Mol Pharm ; 18(1): 386-402, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33296217

RESUMEN

To overcome the challenges of systemic toxicity and weak tumor selectivity caused by traditional antitumor drugs, numerous nanocarrier systems have been developed in recent decades, and their therapeutic effect has been improved to varying degrees. However, because of the drug resistance effect and metastasis involved in tumor recurrence, a single chemotherapy can no longer satisfy the diversified treatment needs. Recently, the application of chemotherapy in combination with thermotherapy as a synergistic approach has been proven to be more effective, and it provides a new strategy for cancer therapy. In this work, by utilizing the unique properties of erythrocytes, a surface-modified erythrocyte membrane was constructed as a novel nanocarrier system (DOX and ICG-PLGA@RBC nanoparticles, DIRNPs for short) for the simultaneous transportation of chemotherapeutic drugs (doxorubicin, DOX) and photothermal agents (indocyanine green, ICG) to achieve the effects of long-term circulation, active tumor targeting, and triggered drug release. The results indicated that DIRNPs have a nanoscale particle size of 158.4 nm with a narrow size distribution and a negative surface charge of -5.79 mV. No particle aggregation or remarkable drug leakage was observed during the 30 day storage test, and because of the excellent photothermal conversion ability of ICG, the local temperature of DIRNPs could dramatically increase from 33.7 to 49.8 °C in 10 min under near-infrared (NIR) laser irradiation. The in vitro drug dissolution data demonstrated that the DOX release from the DIRNPs was pH-dependent and NIR-triggered. Folic acid modifications of the erythrocyte membrane effectively facilitated the intracellular uptake of DIRNPs by HepG2 cells and, as a result, it significantly inhibited tumor cell growth, promoted reactive oxygen species levels, induced cell apoptosis, and restricted cell recovery and migration. In vivo pharmacokinetics and biodistribution studies indicated that the DIRNPs prolonged the half-life of DOX from 6.03 to 17.6 h and remarkably reduced the DOX level in the heart to avoid drug-related cardiotoxicity. More importantly, the DIRNPs exerted excellent in vivo antitumor efficacy against H22 tumors with superior safety. In conclusion, utilizing the advantageous properties of erythrocytes to construct a tumor-targeted biomimetic nanocarrier for codelivery of chemotherapeutics and photothermal agents to produce synergistic effects is considered an effective method for cancer therapy.


Asunto(s)
Antineoplásicos/farmacología , Membrana Eritrocítica/efectos de los fármacos , Ácido Fólico/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Terapia Combinada/métodos , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos/efectos de los fármacos , Células Hep G2 , Humanos , Hipertermia Inducida/métodos , Verde de Indocianina/metabolismo , Ratones , Nanopartículas/administración & dosificación , Fototerapia/métodos , Ratas , Ratas Sprague-Dawley , Distribución Tisular/fisiología
3.
Opt Express ; 26(20): 26009-26019, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-30469694

RESUMEN

Imaging through a wavy water surface is a challenging task, as the wavy water surface introduces anisoplanatism effects difficult to model and track. A typical recovery method is usually involving multiple-stage processing on a pre-acquired image sequence. A new progressive restoration scheme is demonstrated, it can run simultaneously with image acquisition and mitigate both distortion and blur progressively. This method extends the anisotropic evolution in lucky region fusion with a novel progressive optical flow based de-warping scheme, centroid evolution. A comparison has been made with other state-of-art techniques, the proposed method can create comparable results, even with much less frames acquired. Experiments with real through-water scenes have also proved the effectiveness of the method.

4.
Mol Pharm ; 15(12): 5728-5740, 2018 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-30359027

RESUMEN

Anticancer drugs cannot be located in the tumor efficiently when intravenously administered because of their weak tissue specificity and often present the problems of low therapeutic activity and severe adverse effects. To conquer these challenges, a targeting nanomedicine system based on human body cells or cell derivates have drawn more attention from scientists in recent decades. In this work, we used doxorubicin (DOX) as a model drug and a nanoerythrocyte modified with folic acid (FA) and polyethylene glycol (PEG) as a carrier to develop a novel tumor targeting drug delivery system (FA/PEG-DOX-Nano-RBCs) to enhance antitumor efficacy and reduce drug-related toxicity. The results showed that this drug delivery system exhibited inspiring features including nanoscale particle size with uniform distribution, good physicochemical stability, and sustained drug release behavior. Compared with DOX injection, FA/PEG-DOX-Nano-RBCs can greatly prolong the drug circulation time in vivo and upgrade the drug concentration accumulated in tumor tissue. Moreover, FA/PEG-DOX-Nano-RBCs exerted stronger antitumor efficacy in vivo against liver cancer and showed superior safety. In conclusion, a surface-modified nanoerythrocyte was a promising drug delivery vehicle for achieving improved therapeutic efficacy and reduced systemic adverse effects for anticancer drugs.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Eritrocitos/química , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas/química , Administración Intravenosa , Animales , Antibióticos Antineoplásicos/farmacocinética , Línea Celular Tumoral/trasplante , Supervivencia Celular , Modelos Animales de Enfermedad , Doxorrubicina/farmacocinética , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ácido Fólico/química , Humanos , Concentración de Iones de Hidrógeno , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Tamaño de la Partícula , Fosfatidiletanolaminas/química , Polietilenglicoles/química , Ratas , Ratas Sprague-Dawley , Distribución Tisular
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