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1.
J Control Release ; 361: 681-693, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37595667

RESUMO

The two-signal model of T cell activation has helped shape our understanding of the adaptive immune response for over four decades. According to the model, activation of T cells requires a stimulus through the T cell receptor/CD3 complex (signal 1) and a costimulatory signal 2. Stimulation of activatory signals via T cell agonists has thus emerged. However, for a robust T cell activation, it necessitates not only the presence of both signal 1 and signal 2, but also a high signaling strength. Herein, we report a photo-activable nano-agonist for the two-signal model of T cell in vivo activation. A UV-crosslinkable polymer is coated onto upconversion nanoparticles with satisfactory NIR-to-UV light conversion efficiency. Then dual signal molecules, i.e., signal 1 and signal 2, are conjugated to the polymer end to yield the photo-activable T cell nano-agonist. In melanoma and breast cancer models, photo-activable nano-agonist could bind onto corresponding activatory receptors on the surface of T cells, but has limited activity without the application of NIR light (absence of photo-crosslinking of receptors and consequently a poor signaling strength). While when the NIR light is switched on locally, T cells in tumor are remarkably activated and kill tumor cells effectively. Moreover, we do not observe any detectable toxicities related to the photo-activable nano-agonist. We believe with two activatory signals being simultaneously strengthened by local photo-switched crosslinking, T cells realize a robust and selective activation in tumor and, consequently contribute to an enhanced and safe tumor immunotherapy.


Assuntos
Melanoma , Nanopartículas , Humanos , Imunoterapia , Ativação Linfocitária , Polímeros
2.
Zhonghua Yi Xue Za Zhi ; 91(47): 3371-3, 2011 Dec 20.
Artigo em Zh | MEDLINE | ID: mdl-22333208

RESUMO

OBJECTIVE: To prepare compound epirubicin hydrochloride-loaded polymeric nanoparticles of L-lactic-co-glycolic acid and establish their quality control. METHODS: The emulsion-solvent evaporation method was employed to prepare and freeze-dry the compound epirubicin hydrochloride-loaded polymeric nanoparticles of L-lactic-co-glycolic acid after the addition of lactose. The contents and cumulative release of epirubicin hydrochloride and dimeglumine gadopentetate were detected simultaneously by RP-HPLC (reverse phase-high performance liquid chromatography). RESULTS: The above nanoparticles were prepared and the quality standards for simultaneously determining the contents of epirubicin hydrochloride and dimeglumine gadopentetate established primarily. The contents of epirubicin hydrochloride and dimeglumine gadopentetate in compound preparation were 100.6% ± 1.6% and 99.1% ± 1.9% respectively. And two compositions could be completely released within 9 days. CONCLUSION: The preparation method of nanoparticles is simple and their quality control feasible.


Assuntos
Epirubicina/análise , Epirubicina/síntese química , Ácido Láctico/química , Ácido Poliglicólico/química , Tecnologia Farmacêutica/métodos , Portadores de Fármacos , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
3.
Biomaterials ; 217: 119326, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31288173

RESUMO

Spinal cord injury (SCI) leads to immediate disruption of neuronal membranes and loss of neurons, followed by extensive secondary injury process. Treatment of SCI still remains a tremendous challenge clinically. Minocycline could target comprehensive secondary injury via anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms. Polyethylene glycol (PEG), a known sealing agent, is able to seal the damaged cell membranes and reduce calcium influx, thereby exerting neuroprotective capacity. Here, an E-selectin-targeting sialic acid - polyethylene glycol - poly (lactic-co-glycolic acid) (SAPP) copolymer was designed for delivering hydrophobic minocycline to achieve combinational therapy of SCI. The obtained SAPP copolymer could self-assemble into micelles with critical micelle concentration being of 13.40 µg/mL, and effectively encapsulate hydrophobic minocycline. The prepared drug-loaded micelles (SAPPM) displayed sustained drug release over 72 h, which could stop microglia activation and exhibited excellent neuroprotective capacity in vitro. The SAPP micelles were efficiently accumulated in the lesion site of SCI rats via the specific binding between sialic acid and E-selectin. Due to the targeting distribution and combinational effect between PEG and minocycline, SAPPM could obviously reduce the area of lesion cavity, and realize more survival of axons and myelin sheaths from the injury, thus distinctly improving hindlimb functional recovery of SCI rats and conferring superior therapeutic effect in coparison with other groups. Our work presented an effective and safe strategy for SCI targeting therapy. Besides, neuroprotective capacity of PEG deserves further investigation on other central nervous system diseases.


Assuntos
Micelas , Ácido N-Acetilneuramínico/química , Polietilenoglicóis/química , Traumatismos da Medula Espinal/terapia , Animais , Terapia Combinada , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , Microglia/efeitos dos fármacos , Microglia/patologia , Minociclina/farmacologia , Minociclina/uso terapêutico , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Sprague-Dawley , Medula Espinal/patologia , Medula Espinal/ultraestrutura , Traumatismos da Medula Espinal/tratamento farmacológico
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