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1.
Acta Biomater ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729545

RESUMO

Diabetic wound healing is a great clinical challenge due to the microenvironment of hyperglycemia and high pH value, bacterial infection and persistent inflammation. Here, we develop a cascade nanoreactor hydrogel (Arg@Zn-MOF-GOx Gel, AZG-Gel) with arginine (Arg) loaded Zinc metal organic framework (Zn-MOF) and glucose oxidase (GOx) based on chondroitin sulfate (CS) and Pluronic (F127) to accelerate diabetic infected wound healing. GOx in AZG-Gel was triggered by hyperglycemic environment to reduce local glucose and pH, and simultaneously produced hydrogen peroxide (H2O2) to enable Arg to release nitric oxide (NO) for inflammation regulation, providing a suitable microenvironment for wound healing. Zinc ions (Zn2+) released from acid-responsive Zn-MOF significantly inhibited the proliferation and biofilm formation of S.aureus and E.coli. AZG-Gel significantly accelerated diabetic infected wound healing by down-regulating pro-inflammatory tumor necrosis factor (TNF)-α and interleukin (IL)-6, up-regulating anti-inflammatory factor IL-4, promoting angiogenesis and collagen deposition in vivo. Collectively, our nanoreactor cascade strategy combining "endogenous improvement (reducing glucose and pH)" with "exogenous resistance (anti-bacterial and anti-inflammatory)" provides a new idea for promoting diabetic infected wound healing by addressing both symptoms and root causes. STATEMENT OF SIGNIFICANCE: A cascade nanoreactor (AZG-Gel) is constructed to solve three key problems in diabetic wound healing, namely, hyperglycemia and high pH microenvironment, bacterial infection and persistent inflammation. Local glucose and pH levels are reduced by GOx to provide a suitable microenvironment for wound healing. The release of Zn2+ significantly inhibits bacterial proliferation and biofilm formation, and NO reduces wound inflammation and promotes angiogenesis. The pH change when AZG-Gel is applied to wounds is expected to enable the visualization of wound healing to guide the treatment of diabetic wound. Our strategy of "endogenous improvement (reducing glucose and pH)" combined with "exogenous resistance (anti-bacterial and anti-inflammatory)" provides a new way for promoting diabetic wound healing.

2.
Biomaterials ; 306: 122472, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38280315

RESUMO

Immunotherapy has emerged as a promising strategy against tumors. However, its efficacy is limited by low immunogenicity, poor antigen presentation, and inadequate lymphocyte infiltration. Herein, we develop a nanoplatform (Mn-HSP) loaded with manganese ions (Mn2+) and paclitaxel (PTX) prodrug based on hyaluronic acid. PTX in Mn-HSP induces DNA damage and pyroptosis to release tumor-associated antigens (TAAs), enhancing tumor-specific adaptive immunity. Meanwhile, Mn2+ in Mn-HSP, together with PTX-induced DNA damage, activates the stimulator of interferon gene (STING) pathway to amplify innate immunity. Mn-HSP combines with adaptive and innate immunity, effectively enhancing the presentation of antigen-presenting cells (APCs) and promoting tumor infiltration of cytotoxic T lymphocytes (CTLs). In turn, the granzyme B (GZMB) secreted by CTLs triggers pyroptosis again, thereby establishing a "circulating immunotherapy" against tumors. Our results demonstrate that Mn-HSP efficiently inhibits primary breast tumors, as well as rechallenge tumors and lung metastasis in vivo. Therefore, the circulating immunotherapy that combines pyroptosis mediated adaptive immunity and STING pathway amplified innate immunity provides a novel strategy for enhancing tumor immunotherapy.


Assuntos
Neoplasias Pulmonares , Neoplasias , Humanos , Piroptose , Transporte Biológico , Imunidade Adaptativa , Imunoterapia , Neoplasias/tratamento farmacológico
3.
Adv Healthc Mater ; 13(4): e2302597, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37941492

RESUMO

Photodynamic therapy (PDT) is a promising approach for tumor treatment; however, the therapeutic resistance of cancer stem cells (CSCs) severely limits its efficacy and easily lead to recurrence. Herein, a hyaluronic acid (HA)-Ce6-Olaparib (OLA) micelle (HCCO) is developed, which combines the CSC targeting of HA, the PDT effect of Ce6, and the DNA damage repair inhibition of OLA. More importantly, HCCO induces immunogenic cell death (ICD) effects, promotes dendritic cells maturation, and alleviates myeloid-derived suppressor cells (MDSCs) infiltration to reverse CSC resistance. As a result, HCCO not only significantly inhibits the growth of 4T1 breast cancer cells and CSCs in vitro, but also effectively inhibits tumor recurrence and metastasis in vivo. This study provides a novel strategy for preventing tumor recurrence and metastasis by the combination of inhibiting DNA damage repair, reversing CSC resistance, and enhancing PDT.


Assuntos
Ácido Hialurônico , Fotoquimioterapia , Humanos , Ácido Hialurônico/farmacologia , Ácido Hialurônico/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/metabolismo
4.
Small ; 20(5): e2305728, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37752692

RESUMO

Immunotherapy is regarded as a prospective strategy against metastatic cancer. However, tumor-associated macrophages (TAMs), which accumulate in hypoxic tumor microenvironment, reduce the effectiveness of immunotherapy by blocking or "hijacking" the initiation of the immune response. Here, a novel tumor-targeted nanoplatform loaded with hypoxia-pathway-intervened docosahexaenoic acid (DHA) and chemotherapeutic drug carfilzomib (CFZ) is developed, which realizes the rescue of TAM-hijacked immune response and effective metastatic cancer immunotherapy. DHA is conjugated to fucoidan (Fuc) via a reduction cleavable selenylsulfide bond (SSe) for micelle preparation, and CFZ is encapsulated in the hydrophobic cores of micelles. The functionalized nanoplatforms (Fuc─SSe─DHA (FSSeD)-CFZs) induce immunogenic cell death, inhibit hypoxia-inducible factor-1α expression, and improve immunosuppression by TAM suppression. FSSeD-CFZs enhance immune response against primary tumor development and metastasis formation. In brief, the novel rescue strategy for TAM-hijacked immunoreaction by inhibiting hypoxia pathway has the potential and clinically translational significance for enhanced metastatic cancer immunotherapy.


Assuntos
Macrófagos , Neoplasias , Humanos , Macrófagos/metabolismo , Neoplasias/patologia , Imunoterapia , Hipóxia/metabolismo , Hipóxia/patologia , Micelas , Imunidade , Microambiente Tumoral , Linhagem Celular Tumoral
5.
Acta Biomater ; 171: 565-579, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37716479

RESUMO

In clinical chemotherapy, albumin-bound paclitaxel (Abraxane) can improve the tumor targeting property and therapeutic efficacy of paclitaxel (PTX) against orthotopic malignancies. However, patients with metastatic cancer have a poor prognosis, probably due to the instability, chemoresistance, and inability of albumin-bound paclitaxel to alter the tumor microenvironment. Here we propose a new biguanide-modified albumin-based nanoplatform that encapsulates paclitaxel for the effective treatment of metastatic cancer. The PTX is encapsulated in poly (lactic-co-glycolic acid) cores coated with biguanide-modified albumin (HSA-NH). The functionalized nanoparticles (HSA-NH NPs) exhibit a remarkable stable profile with low drug release (P < 0.05 versus Abraxane), target tumor tissues, suppress epithelial-mesenchymal transition (EMT) events for anti-metastatic effects, and reduce the phenotype of cancer stem cells. As a result, HSA-NH NPs effectively prolong animal survival (55 days) by inhibiting not only primary tumor growth but also metastasis. This study provides proof of concept that the biguanide-anchored albumin-based nanoplatform encapsulating PTX is a powerful, safe, and clinically translational strategy for the treatment of metastatic cancer. STATEMENT OF SIGNIFICANCE: Albumin-bound paclitaxel (Abraxane) can increase paclitaxel's tumor targeting and therapeutic efficacy in clinical cancer treatments such as breast cancer. However, the instability, chemoresistance, and lack of tumor microenvironment modulation of albumin-bound paclitaxel may lead to poor therapeutic efficacy in metastatic cancer patients. Here we develop biguanide-anchored albumin-based nanoplatforms that encapsulate paclitaxel (HSA-NH NPs) for metastatic cancer treatment. Poly(lactic-co-glycolic acid) (PLGA) cores encapsulating paclitaxel improve the stability of HSA-NH NPs. Based on the activities of metformin, biguanide-anchored albumin adsorbed on PLGA cores improves paclitaxel efficacy, inhibits various aberrant changes during epithelial-mesenchymal transition, and reduces tumor cell stemness. The biguanide-anchored albumin-based nanoplatform encapsulating PTX can serve as a potent, safe, and clinically translational approach for metastatic cancer therapies.


Assuntos
Nanopartículas , Neoplasias , Animais , Humanos , Paclitaxel Ligado a Albumina , Biguanidas/farmacologia , Biguanidas/uso terapêutico , Transição Epitelial-Mesenquimal , Linhagem Celular Tumoral , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Albuminas/farmacologia , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico
6.
Int J Biol Macromol ; 252: 126358, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37598824

RESUMO

Recurrence and metastasis have been recognized as a great challenge in cancer treatment. Cancer stem cells (CSCs), as a small subset of cancer cells, are closely associated with tumor metastasis and recurrence due to their resistance and multi-differentiation characteristics. Herein, we developed a local injectable hyaluronic acid (HA) composite hydrogel (HAAG) that targets CSCs, which can continuously release all-trans retinoic acid (ATRA) and gold nanoparticles (AuNPs) at tumor sites. The composite hydrogel was endowed with the ability to target CSCs through the specific binding of HA to CD44. ATRA was loaded into HA micelles to induce CSCs to differentiate into normal cancer cells, while AuNPs was incorporated into the hydrogel for photothermal therapy (PTT). HAAG exhibited good injectability, photothermal properties and CSCs targeting ability. HAAG not only significantly inhibited the growth of 4T1 mouse breast cancer cells and 4T1-CSCs in vitro, but also effectively inhibited tumor recurrence and metastasis in a 4T1-CSC mouse model in vivo. Our study provides a novel strategy of local differentiation combined with PTT for inhibiting the recurrence and metastasis of breast cancer.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Animais , Camundongos , Ácido Hialurônico/química , Ouro/farmacologia , Ouro/metabolismo , Hidrogéis/farmacologia , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/patologia , Nanopartículas/química , Tretinoína/farmacologia , Células-Tronco Neoplásicas/metabolismo
7.
ACS Appl Mater Interfaces ; 15(34): 40267-40279, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37594128

RESUMO

Transdermal cancer therapy faces great challenges in clinical practice due to the low drug transdermal efficiency and the unsatisfactory effect of monotherapy. Herein, we develop a novel bubble pump microneedle system (BPMN-CuS/DOX) by embedding sodium bicarbonate (NaHCO3) into hyaluronic acid microneedles (MNs) loaded with fucoidan-based copper sulfide nanoparticles (Fuc-CuS NPs) and doxorubicin (DOX). BPMN-CuS/DOX can generate CO2 bubbles triggered by an acidic tumor microenvironment for deep and rapid intradermal drug delivery. Fuc-CuS NPs exhibit excellent photothermal effect and Fenton-like catalytic activity, producing more reactive oxygen species (ROS) by photothermal therapy (PTT) and chemodynamic therapy (CDT), which enhances the antitumor efficacy of DOX and reduces the dosage of its chemotherapy (CT). Simultaneously, DOX increases intracellular hydrogen peroxide (H2O2) supplementation and promotes the sustained production of ROS. BPMN-CuS/DOX significantly inhibits melanoma both in vitro and in vivo by the combination of CDT, PTT, and CT. In short, our study significantly enhances the effectiveness of transdermal drug delivery by constructing BPMNs and provides a promising novel strategy for transdermal cancer treatment with multiple therapies.


Assuntos
Melanoma , Melanoma/terapia , Sulfato de Cobre/química , Terapia Fototérmica , Doxorrubicina/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Terapia Combinada , Masculino , Animais , Camundongos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL
8.
Biomacromolecules ; 24(8): 3755-3766, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37506051

RESUMO

The DNA damage repair of tumor cells limits the effect of photothermal therapy (PTT), and high temperatures induced by PTT can damage adjacent normal tissues. To overcome these limitations, we developed a novel composite hydrogel (OLA-Au-Gel) based on chitosan (CS) and ß-glycerophosphate (ß-GP), which encapsulated olaparib-liposomes (OLA-lips) and CS-capped gold nanoparticles (CS-AuNPs). OLA-Au-Gel achieved the combination of mild PTT (mPTT) by CS-AuNPs and tumor DNA damage repair inhibition by OLA. The hydrogel showed good biocompatibility, injectability, and photothermal response. Under near-infrared laser irradiation, OLA-Au-Gel inhibited the proliferation of tumor cells, induced the generation of reactive oxygen species in vitro, and effectively inhibited the growth of breast tumors in vivo. OLA-Au-Gel shows a promising application prospect for inhibiting tumor development and improving the antitumor effect. Collectively, we propose a novel strategy for enhanced antitumor therapy based on the combination of mPTT and DNA damage repair inhibition.


Assuntos
Quitosana , Nanopartículas Metálicas , Neoplasias , Humanos , Hidrogéis/farmacologia , Ouro , Terapia Fototérmica , Dano ao DNA , Linhagem Celular Tumoral
9.
ACS Appl Mater Interfaces ; 15(19): 22830-22842, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37129874

RESUMO

Antibiotic resistance reduces the effectiveness of infected wound healing, and it is necessary to develop a new strategy to promote infected wound healing without using antibiotics. Here, we develop a Chlorin e6 (Ce6)-loaded zinc-metal-organic framework (MOF) thermosensitive hydrogel (Ce6@MOF-Gel) based on alginate and poly(propylene glycol) 407, which enhances antibacterial effects and promotes infected wound healing by a novel strategy of combining zinc-MOF with photodynamic therapy (PDT). Zinc-MOF can realize acid-responsive release of Ce6 and improve antibacterial performance without drug resistance by destroying the integrity of bacterial cell membranes and enhancing the production of bacterial reactive oxygen species (ROS). Additionally, Ce6@MOF-Gel enhances the stability, solubility, and photodynamic properties of Ce6. More importantly, Ce6@MOF-Gel reduces inflammation and promotes collagen deposition and re-epithelialization to facilitate infected wound healing. Collectively, the photodynamic MOF-based hydrogel provides a new, efficient, and safe way for accelerated healing of infected wounds.


Assuntos
Estruturas Metalorgânicas , Fotoquimioterapia , Estruturas Metalorgânicas/farmacologia , Hidrogéis/farmacologia , Alginatos/farmacologia , Antibacterianos/farmacologia , Cicatrização
10.
Carbohydr Polym ; 312: 120837, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37059562

RESUMO

Programmed cell death-ligand 1 (PD-L1) small interfering RNA (siRNA) achieves tumor immunotherapy by restoring the immune response of T cells, but the efficacy of PD-1/PD-L1 monotherapy is relatively low. While immunogenic cell death (ICD) can improve the response of most tumors to anti-PD-L1 and enhance tumor immunotherapy. Herein, a targeting peptide GE11-functionalized dual-responsive carboxymethyl chitosan (CMCS) micelle (G-CMssOA) is developed for simultaneous delivery of PD-L1 siRNA and doxorubicin (DOX) in a complex form of DOX·PD-L1 siRNA (D&P). The complex-loaded micelles (G-CMssOA/D&P) have good physiological stability and pH/reduction responsiveness, and improve the intratumoral infiltration of CD4+ and CD8+ T cells, reduce Tregs (TGF-ß), and increase the secretion of immune-stimulatory cytokine (TNF-α). The combination of DOX-induced ICD and PD-L1 siRNA-mediated immune escape inhibition significantly improves anti-tumor immune response and inhibits tumor growth. This complex delivery strategy provides a new approach for effectively delivering siRNA and enhancing anti-tumor immunotherapy.


Assuntos
Quitosana , Micelas , RNA Interferente Pequeno , Linfócitos T CD8-Positivos , Morte Celular Imunogênica , Linhagem Celular Tumoral , Doxorrubicina/farmacologia
11.
Nano Lett ; 23(4): 1327-1336, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36749122

RESUMO

Deep cutaneous fungal infection (DCFI) is difficult to be treated by the traditional topical application due to low drug transdermal efficiency, poor fungicidal effect, and easy to develop drug resistance. Here, we report a novel biodegradable microneedle patch (CuS/PAF-26 MN) for DCFI treatment. CuS/PAF-26 MN is composed of hyaluronic acid (HA) and sodium carboxymethylcellulose (CMC-Na), which can simultaneously deliver copper sulfide nanoenzyme (CuS NE) and antimicrobial peptide (PAF-26). CuS NE catalyzes hydrogen peroxide to produce reactive oxygen species (ROS), and PAF-26 directly destroys the cell membrane of fungi. The combination of ROS toxicity produced by CuS NE and the destruction of fungal membrane by PAF-26 shows strong antifungal activities without drug resistance. The antifungal effect of CuS/PAF-26 MN is significantly superior to that of traditional ointment, CuS MN or PAF-26 MN in a DCFI mouse model. Therefore, CuS/PAF-26 MN shows a promising application prospect for treating DCFI.


Assuntos
Ácido Hialurônico , Micoses , Camundongos , Animais , Espécies Reativas de Oxigênio , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Administração Cutânea , Resistência a Medicamentos
12.
Carbohydr Polym ; 298: 120123, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36241295

RESUMO

Tumor surgery is often accompanied by tumor residue, tissue defects, bleeding, and bacterial infection, which can easily cause tumor recurrence, low survival rates, and delay wound healing. In this study, a multifunctional hydrogel (CA-AuAgNPs-Gel) was developed to prevent tumor recurrence and promote wound healing after tumor surgery in the absence of chemotherapeutic drugs and antibiotics. CA-AuAgNPs-Gel was prepared using iota carrageenan (CA)-capped gold­silver nanoparticles (CA-AuAgNPs) and poloxamer 407 (F127), which exhibited good biocompatibility, injectability, and near-infrared (NIR) photothermal responsiveness. CA-AuAgNPs-Gel inhibited the growth of 4T1 breast cancer in situ and the recurrence of surgically resected B16F10 melanoma. It also effectively stopped bleeding and promoted tumor postsurgical wound healing in vivo. Importantly, CA-AuAgNPs-Gel induced tumor apoptosis via photothermal-induced hyperthermia and immunogenic cell death (ICD) under NIR laser radiation. Collectively, this hydrogel shows significant clinical application prospects for inhibiting tumor recurrence and promoting wound healing for postsurgical tumor treatment.


Assuntos
Hidrogéis , Nanopartículas Metálicas , Antibacterianos/química , Carragenina/farmacologia , Ouro/farmacologia , Humanos , Hidrogéis/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Poloxâmero , Prata/farmacologia , Cicatrização
13.
Int J Biol Macromol ; 222(Pt A): 1078-1091, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183754

RESUMO

The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/D@HAssOA) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/D@HAssOA are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4+/CD8+ T cells by silencing PD-L1 expression. In vivo studies show that R/C/D@HAssOA exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.


Assuntos
Neoplasias da Mama , Quitosana , Humanos , Feminino , Micelas , Ácido Hialurônico , Linfócitos T CD8-Positivos , Doxorrubicina/farmacologia , Oxirredução , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Microambiente Tumoral
14.
Int J Biol Macromol ; 219: 1087-1099, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36049562

RESUMO

Timely hemostasis, antibacterial activity, and good adhesion are essential for wound healing. Here, we report about a novel nanocomposite hydrogel with hemostatic, antibacterial, and adhesive properties constructed with a mussel-inspired strategy. Oxidized alginic acid, dopamine, and antimicrobial peptide ε-polylysine were used to prepare a nanocomposite (ODP), and then further cross-linked with acrylamide to fabricate a nanocomposite hydrogel (ODPA). ODPA hydrogel can adhere to the surface of bleeding organs and arrest bleeding within 30 s. It can also be stretched to 12 times its original length and withstand a compression strain of 40 %, and shows effective inhibition on gram-positive and gram-negative bacteria. Compared with commercial alginate sponge, ODPA hydrogel can accelerate the healing of infected full-thickness wound by reducing inflammation, promoting angiogenesis, and collagen deposition. Therefore, the nanocomposite hydrogel is expected to be a multifunctional dressing for promoting healing of infected wounds.


Assuntos
Hemostáticos , Infecção dos Ferimentos , Acrilamidas/farmacologia , Alginatos/química , Ácido Algínico/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Antimicrobianos , Colágeno/química , Dopamina/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Hemostáticos/farmacologia , Humanos , Hidrogéis/química , Nanogéis , Polilisina/farmacologia , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico
15.
J Nanobiotechnology ; 20(1): 394, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045429

RESUMO

Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an anti-inflammatory therapeutic with highlighted safety and efficacy is deficient. Metformin is a promising anti-inflammatory agent with low side effects, but tumor monotherapy with an anti-inflammation drug could generate therapy resistance, cell adaptation or even promote tumor development. Combination therapies with various anti-inflammatory mechanisms can be favorable options improving therapeutic effects of metformin, here we develop a tumor targeting hybrid micelle based on metformin and a histone deacetylase inhibitor propofol-docosahexaenoic acid for efficient therapeutic efficacies of anti-inflammatory drugs. Triptolide is further encapsulated in hybrid micelles for orthotopic tumor therapies. The final multifunctional nanoplatforms (HAOPTs) with hyaluronic acid (HA) modification can target tumor efficiently, inhibit tumor cell EMT processes, repress metastasis establishment and suppress metastatic tumor development in a synergistic manner. Collectively, the results afford proof of concept that the tumor targeting anti-inflammatory nanoplatform can provide a potent, safe and clinical translational approach for EMT inhibition and metastatic tumor therapy.


Assuntos
Metformina , Neoplasias , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Metformina/farmacologia , Metformina/uso terapêutico
16.
Sensors (Basel) ; 22(3)2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35161845

RESUMO

Silicon Photomultiplier (SiPM) is a sensor that can detect low-light signals lower than the single-photon level. In order to study the properties of neutrinos at a low detection threshold and low radioactivity experimental background, a low-temperature CsI neutrino coherent scattering detector is designed to be read by the SiPM sensor. Less thermal noise of SiPM and more light yield of CsI crystals can be obtained at the working temperature of liquid nitrogen. The breakdown voltage (Vbd) and dark count rate (DCR) of SiPM at liquid nitrogen temperature are two key parameters for coherent scattering detection. In this paper, a low-temperature test is conducted on the mass-produced ON Semiconductor J-Series SiPM. We design a cryogenic system for cooling SiPM at liquid nitrogen temperature and the changes of operating voltage and dark noise from room to liquid nitrogen temperature are measured in detail. The results show that SiPM works at the liquid nitrogen temperature, and the dark count rate drops by six orders of magnitude from room temperature (120 kHz/mm2) to liquid nitrogen temperature (0.1 Hz/mm2).

17.
Life (Basel) ; 11(12)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34947903

RESUMO

The SARS-CoV-2 virus is deadly, contagious, can cause COVID-19 disease, and endangers public health and safety. The development of SARS-CoV-2 inactivation technology is crucial and imminent in current pandemic period. Neutron radiation is usually used to sterilize viruses because neutron radiation is 10 times more effective than gamma-rays in inactivating viruses. In this work we established a closed SARS-CoV-2 inactivation container model by the Monte Carlo method and simulated the inactivation performance by using several different neutrons sources. To study the effects of inactivation container factors, including the reflector thickness, the type of the reflector material, the SARS-CoV-2 layer area and the distance from the radiation source on the energy deposition of a single neutron particle in SARS-CoV-2 sample, we simulated the neutron energy deposition on a SARS-CoV-2 sample. The simulation results indicate that the saturated thicknesses of reflector materials for graphite, water and paraffin are approximately 30 cm, 15 cm, and 10 cm, respectively, and the energy deposition (radiation dose) becomes larger when the SARS-CoV-2 layer area is smaller and the SARS-CoV-2 layer is placed closer to the neutron source. The calculated single-neutron energy deposition on 10 × 10 cm2 SARS-CoV-2 layer is about 3.0059 × 10-4 MeV/g with graphite as the reflection layer, when the 14 MeV neutron source intensity is 1012 n/s and the SARS-CoV-2 layer is 5 cm away from the neutron source. If the lethal dose of SARS-CoV-2 is assumed as the IAEA recommended reference dose, 25 kGy, the SARS-CoV-2 could be decontaminated in about 87 min, and the sterilization time could be less than 52 s if the 14 MeV neutron intensity is increased to 1014 n/s.

18.
Carbohydr Polym ; 269: 118258, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34294293

RESUMO

Marine polysaccharides or oligosaccharides have potential to promote wound healing due to their biocompatibility and physicochemical properties. However, microbial infection delays wound healing process, and novel antimicrobial wound dressings are urgently needed. Here, agarose oligosaccharides (AGO) obtained from marine red algae were used as a reducing and stabilizer for green synthesis of silver nanoparticles (AgNPs), and further successfully connected with odorranain A (OA), one of antimicrobial peptides (AMPs), to obtain a novel composite nanomaterial (AGO-AgNPs-OA). Transmission electron microscopy (TEM) and Malvern particle size analyzer showed that AGO-AgNPs-OA was spherical or elliptic with average size of about 100 nm. Circular dichroism (CD) spectroscopy showed that AGO-AgNPs stabilized the α-helical structure of OA. AGO-AgNPs-OA showed stronger anti-bacterial activities than AGO-AgNPs, and had good biocompatibility and significant promoting effect on wound healing. Our data suggest that AMPs conjugated marine oligosaccharides and AgNPs may be effective and safe antibacterial materials for wound therapy.


Assuntos
Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Bandagens , Nanopartículas Metálicas/uso terapêutico , Sefarose/química , Cicatrização/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Antifúngicos/química , Antifúngicos/toxicidade , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/toxicidade , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Testes de Sensibilidade Microbiana , Oligossacarídeos/síntese química , Oligossacarídeos/química , Oligossacarídeos/toxicidade , Ratos Sprague-Dawley , Rodófitas/química , Sefarose/síntese química , Sefarose/toxicidade , Prata/química , Prata/uso terapêutico , Prata/toxicidade , Pele/efeitos dos fármacos
19.
Carbohydr Polym ; 266: 118100, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34044919

RESUMO

Moist, breathable and antibacterial microenvironment can promote cell proliferation and migration, which is beneficial to wound healing. Here, we fabricated a novel sodium alginate-chitosan oligosaccharide­zinc oxide (SA-COS-ZnO) composite hydrogel by spontaneous Schiff base reaction, using aldehydated sodium alginate (SA), chitosan oligosaccharide (COS), and zinc oxide (ZnO) nanoparticles, which can provide a moist and antibacterial environment for wound healing. The porosity and swelling degree of SA-COS-ZnO hydrogel are 80% and 150%, respectively, and its water vapor permeability is 682 g/m2/24h. The composite hydrogel showed good biocompatibility to blood cells, 3T3 cells, and 293T cells, and significant antibacterial activity against Escherichia coli, Staphylococcus aureus, Candida albicans, and Bacillus subtilis. Moreover, the hydrogel showed a promoting effect on wound healing in a rat scald model. The present study suggests that marine carbohydrates composite hydrogels are promising in wound care management.


Assuntos
Anti-Infecciosos/uso terapêutico , Hidrogéis/uso terapêutico , Polissacarídeos/uso terapêutico , Cicatrização/efeitos dos fármacos , Óxido de Zinco/uso terapêutico , Alginatos/química , Alginatos/uso terapêutico , Alginatos/toxicidade , Animais , Anti-Infecciosos/química , Anti-Infecciosos/toxicidade , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Linhagem Celular , Quitina/análogos & derivados , Quitina/química , Quitina/uso terapêutico , Quitina/toxicidade , Quitosana , Escherichia coli/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Hidrogéis/química , Hidrogéis/toxicidade , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanopartículas/toxicidade , Oligossacarídeos , Polissacarídeos/química , Polissacarídeos/toxicidade , Porosidade , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos , Óxido de Zinco/química , Óxido de Zinco/toxicidade
20.
Materials (Basel) ; 14(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807405

RESUMO

We investigated H2O molecule adsorption that had an effect on the luminescence properties of the CsI(Na) crystal using experiments and first-principle calculations. We measured the emission spectra of the CsI(Na) crystal at different exposure times under gamma ray excitation. The experimental results showed that the energy resolution of the CsI(Na) crystal was worse when the crystal surface adsorbed more H2O molecules, and the crystal surface deliquescence decreased the luminescence efficiency of the CsI(Na) crystal. We studied the band structure, density of states, and optical properties changes caused by H2O molecule adsorption on the CsI(Na) (010) surface. The generalized gradient approximation (GGA) was used to describe the exchange and correlation potential between the electrons. Our calculation results showed that the band gap width of the CsI(Na) (010) surface decreased after adsorbing H2O molecules, while three new peaks appeared in the valence band, and the absorption coefficient decreased from 90,000 cm-1 to 65,000 cm-1, and the reflection coefficient decreased from 0.195 to 0.105. Further, the absorption coefficient was reduced by at least 25% because of H2O molecule adsorption, which led to the luminescence degradation of the CsI(Na) crystal.

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