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1.
Int J Mol Sci ; 24(7)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37047668

RESUMO

The cryopreservation of red blood cells (RBCs) holds great potential for ensuring timely blood transfusions and maintaining an adequate RBC inventory. The conventional cryoprotectants (CPAs) have a lot of limitations, and there is an obvious need for novel, efficient, and biocompatible CPAs. Here, it is shown for the first time that the addition of dimethylglycine (DMG) improved the thawed RBC recovery from 11.55 ± 1.40% to 72.15 ± 1.22%. We found that DMG could reduce the mechanical damage by inhibiting ice formation and recrystallization during cryopreservation. DMG can also scavenge reactive oxygen species (ROS) and maintain endogenous antioxidant enzyme activities to decrease oxidative damage during cryopreservation. Furthermore, the properties of thawed RBCs were found to be similar to the fresh RBCs in the control. Finally, the technique for order performance by similarity to ideal solution (TOPSIS) was used to compare the performance of glycerol (Gly), hydroxyethyl starch (HES), and DMG in cryopreservation, and DMG exhibited the best efficiency. This work confirms the use of DMG as a novel CPA for cryopreservation of RBCs and may promote clinical transfusion therapy.


Assuntos
Criopreservação , Gelo , Criopreservação/métodos , Crioprotetores/farmacologia , Crioprotetores/química , Eritrócitos , Estresse Oxidativo
2.
Langmuir ; 38(26): 8012-8020, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35715215

RESUMO

Ca2+ overload has attracted an increasing attention due to its benefit of precise cancer therapy, but its efficacy is limited by the strong Ca2+ excretion of cancer cells. Moreover, monotherapy of Ca2+ overload usually fails to treat tumors satisfactorily. Herein, we develop a multifunctional nanosystem that could induce Ca2+ overload by multipathway and simultaneously produce chemotherapy for synergistic tumor therapy. The nanosystem (CaMSN@CUR) is prepared by synthesizing a Ca-doped mesoporous silica nanoparticle (CaMSN) followed by loading the anticancer drug curcumin (CUR). CaMSN serves as the basis Ca2+ generator to induce Ca2+ overload directly in the intracellular environment by acid-triggered Ca2+ release, while CUR could not only exhibit chemotherapy but also facilitate Ca2+ release from the endoplasmic reticulum to the cytoplasm and inhibit Ca2+ efflux out of cells to further enhance Ca2+ overload. The in vitro and in vivo results show that CaMSN@CUR could exhibit a remarkable cytotoxicity against 4T1 cells and significantly inhibit tumor growth in 4T1 tumor-bearing mice via the synergy of Ca2+ overload and CUR-mediated chemotherapy. It is expected that the designed CaMSN@CUR has a great potential for effective tumor therapy.


Assuntos
Antineoplásicos , Curcumina , Nanopartículas , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Curcumina/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Camundongos , Dióxido de Silício
3.
Nanotechnology ; 26(38): 385101, 2015 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-26317506

RESUMO

The lead ion concentration in bile is considerably higher than in blood, and bile is released into the alimentary tract. Thiol-modified SBA-15 administered orally can combine with lead ions in the alimentary tract. In this paper, the in vitro lead absorption of bile was investigated. This thiol-modified SBA-15 material was used in pharmacodynamics studies on rabbits. The result that the lead content in faeces was notably higher indicates that thiol-modified SBA-15 can efficiently remove lead. The mechanism could include the following: thiol-modified SBA-15 material cuts off the heavy metal lead recirculation in the process of bile enterohepatic circulation by chelating the lead in the alimentary tract, causing a certain proportion of lead to be removed by the thiol mesoporous material, and the lead is subsequently egested out of the body in faeces. The results indicate that this material might be a potential non-injection material for the removal bodily heavy metal lead in the alimentary tract. This material may also be a useful means of lead removal, especially for non-acute sub-poisoning symptoms.


Assuntos
Bile/metabolismo , Chumbo/isolamento & purificação , Nanoestruturas/uso terapêutico , Adsorção , Animais , Fezes , Chumbo/sangue , Chumbo/metabolismo , Chumbo/farmacocinética , Intoxicação por Chumbo/tratamento farmacológico , Microscopia Eletrônica de Transmissão e Varredura , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Coelhos , Compostos de Sulfidrila/química , Difração de Raios X
4.
ACS Biomater Sci Eng ; 10(7): 4259-4268, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38832439

RESUMO

Cryopreservation of red blood cells (RBCs) plays an indispensable role in modern clinical transfusion therapy. Researchers are dedicated to finding cryoprotectants (CPAs) with high efficiency and low toxicity to prevent RBCs from cryopreservation injury. This study presents, for the first time, the feasibility and underlying mechanisms of a novel CPA called tris(hydroxymethyl)aminomethane-3-propanesulfonic acid (TAPS) in RBCs cryopreservation. The results demonstrated that the addition of TAPS achieved a post-thaw recovery of RBCs at 79.12 ± 0.67%, accompanied by excellent biocompatibility (above 97%). Subsequently, the mechanism for preventing RBCs from cryopreservation injury was elucidated. On one hand, TAPS exhibits a significant amount of bound water and effectively inhibits ice recrystallization, thereby reducing mechanical damage. On the other hand, TAPS demonstrates high capacity to scavenge reactive oxygen species and strong endogenous antioxidant enzyme activity, providing effective protection against oxidative damage. Above all, TAPS can be readily removed through direct washing, and the RBCs after washing showed no significant differences in various physiological parameters (SEM, RBC hemolysis, ESR, ATPase activity, and Hb content) compared to fresh RBCs. Finally, the presented mathematical modeling analysis indicates the good benefits of TAPS. In summary, TAPS holds potential for both research and practical in the field of cryobiology, offering innovative insights for the improvement of RBCs cryopreservation in transfusion medicine.


Assuntos
Criopreservação , Crioprotetores , Eritrócitos , Eritrócitos/fisiologia , Criopreservação/métodos , Humanos , Crioprotetores/farmacologia , Crioprotetores/química , Preservação de Sangue/métodos , Hemólise , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular
5.
ACS Appl Mater Interfaces ; 16(31): 40739-40752, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39047081

RESUMO

Oxidative stress (OS) is a major mediator of secondary brain injury following intracerebral hemorrhage (ICH). Thus, antioxidant therapy is emerging as an attractive strategy to combat ICH. To achieve both reactive oxygen species (ROS) scavenging ability and on-demand drug release ability, we constructed a novel polydopamine (PDA)-coated diselenide-bridged mesoporous silica nanoparticle (DSeMSN) drug delivery system (PDA-DSeMSN). Edaravone (Eda) was blocked in the pores of DSeMSN by covering the pores with PDA as a gatekeeper. The drug maintained nearly "zero release" before reaching the lesion site, while in the ROS-enriched circumstances, the PDA shell went through degradation and the doped diselenide bonds broke up, triggering the disintegration of nanoparticles and leading to Eda release. Interestingly, the ROS-degradable property of the PDA shell and diselenide bond endowed the system with enhanced ROS-eliminating capacity. The synergistic effect of ROS-responsive drug delivery and ROS-scavenging PDA-DSeMSN showed efficient antioxidative and mitochondria protective performance without apparent toxicity in vitro. Importantly, PDA-DSeMSN@Eda through intravenous administration specifically accumulated in perihematomal sites and demonstrated robust neuroprotection in an ICH mouse model through antioxidative and antiapoptotic effects with high biological safety. Thus, the PDA-DSeMSN platform holds tremendous potential as an excellent carrier for on-demand delivery of drugs and provides a new and effective strategy for the clinical treatment of ICH.


Assuntos
Hemorragia Cerebral , Edaravone , Indóis , Nanopartículas , Espécies Reativas de Oxigênio , Dióxido de Silício , Animais , Dióxido de Silício/química , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/patologia , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Nanopartículas/química , Edaravone/química , Edaravone/farmacologia , Indóis/química , Indóis/farmacologia , Porosidade , Polímeros/química , Polímeros/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Masculino , Antioxidantes/química , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos
6.
J Mater Chem B ; 11(45): 10822-10835, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37920970

RESUMO

The high glutathione (GSH) concentration and insufficient H2O2 content in tumor cells strongly constrict the efficacy of Fenton reaction-based chemodynamic therapy (CDT). Despite numerous efforts, it still remains a formidable challenge for achieving satisfactory efficacy using CDT alone. Herein, an intelligent tetrasulfide bond-bridged mesoporous organosilica-based nanoplatform that integrates GSH-depletion, H2S generation, self-supplied H2O2, co-delivery of doxorubicin (DOX) and Fenton reagent Fe2+ is presented for synergistic triple-enhanced CDT/chemotherapy/H2S therapy. Because the tetrasulfide bond is sensitive to GSH, the nanoplatform can effectively consume GSH, leading to ROS accumulation and H2S generation in the GSH-overexpressed tumor microenvironment. Meanwhile, tetrasulfide bond-induced GSH-depletion triggers the degradation of nanoparticles and the release of DOX and Fe2+. Immediately, Fe2+ catalyzes endogenous H2O2 to highly toxic hydroxyl radicals (˙OH) for CDT, and H2S induces mitochondria injury and causes energy deficiency. Of note, H2S can also decrease the decomposition of H2O2 to augment CDT by downregulating catalase. DOX elicits chemotherapy and promotes H2O2 production to provide a sufficient substrate for enhanced CDT. Importantly, the GSH depletion significantly weakens the scavenging effect on the produced ˙OH, guaranteeing the enhanced and highly efficient CDT. Based on the synergistic effect of triple-augmented CDT, H2S therapy and DOX-mediated chemotherapy, the treatment with this nanoplatform gives rise to a superior antitumor outcome.


Assuntos
Doxorrubicina , Peróxido de Hidrogênio , Doxorrubicina/farmacologia , Glutationa , Radical Hidroxila , Mitocôndrias
7.
ACS Appl Mater Interfaces ; 15(51): 59175-59188, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38095444

RESUMO

Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO2 and dihydroartemisinin (DHA) (LIPSe@CuO2&DHA) is developed to boost ROS generation against tumor. The liposomal nanosystem can degrade in the ROS-overexpressed TME and liberate CuO2 and DHA to initiate Cu-based dual-catalytic ROS generation. Serving as generators of H2O2 and Cu2+, CuO2 can self-produce plenty of toxic hydroxyl radicals via Fenton-like reaction in the acidic TME. Meanwhile, the released Cu2+ can catalyze DHA to generate cytotoxic C-centered radicals. Together, the self-supplied H2O2 and Cu-based dual-catalytic reaction greatly increase the intratumoral level of lethal ROS. Importantly, Cu2+ can decrease the GSH-mediated scavenging effect on the produced ROS via a redox reaction and undergo a Cu2+-to-Cu+ conversion to enhance the Fenton-like reaction, further guaranteeing the high efficiency of ROS generation. Resultantly, LIPSe@CuO2&DHA induces remarkable cancer cell death and tumor growth inhibition, which may present a promising nanocatalytic medicine for cancer therapy.


Assuntos
Nanomedicina , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Peróxido de Hidrogênio/farmacologia , Neoplasias/patologia , Fototerapia , Microambiente Tumoral , Glutationa/farmacologia
8.
Int J Pharm ; 645: 123371, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37673279

RESUMO

Maillard reaction in pharmaceutical preparations refers to a complex chemical reaction existing between reducing excipients and amino-containing drugs in preparations, which can cause a series of quality problems in preparations. Maillard reaction belongs to chemical incompatibility in preparations, and measures should be taken to reduce or avoid it. In this study, the effect of cyclodextrins (commonly used pharmaceutical excipients) on the Maillard reaction and its mechanism in the lysine hydrochloride-lactose solid preparation model were explored for the first time. Our research results show that the embedding of lysine in cyclodextrin can inhibit the Maillard reaction of lysine to some extent, and the embedding of lysine in cyclodextrin with different structures has differences in the inhibitory effects on Maillard reaction.Among the five cyclodextrins we studied, α-CD and HP-ß-CD embedded lysine can reduce Maillard reaction to a greater extent. We suspect that this may be related to the stability of the embedded substance, which needs further study and verification. And our research shows that the inclusion complex between lysine and cyclodextrin may be the result of hydrogen bond, electrostatic attraction, hydrophobic interaction and van der Waals force. Cyclodextrin is expected to solve the problem of Maillard reaction in pharmaceutical industry to some extent.

9.
J Mater Chem B ; 11(35): 8433-8448, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37577774

RESUMO

Mitochondria-targeted copper-depletion is emerging as an attractive strategy to combat cancer. However, existing copper molecular chelators are non-specific, toxic and ineffective. Here, it is reported that multifunctional nanoparticles (MSN-TPP/BNA-DPA) can not only target mitochondria to deprive copper ions to trigger copper-depletion therapy, but also serve as nanocarriers to deliver anticancer drugs for chemotherapy, which are engineered by conjugating a fluorophore 4-bromo-1,8-naphthalicanhydride (BNA), a copper-depriving moiety dimethylpyridinamine (DPA) and a mitochondrial targeting ligand triphenylphosphonium (TPP) on the surface of mesoporous silica nanoparticles (MSN). BNA and the internal charge transfer of compound BNA-DPA endow MSN-TPP/BNA-DPA with green fluorescence emission upon UV excitation, which can be used to monitor the cellular uptake of nanoparticles. When copper ions bind to DPA, green fluorescence is quenched, providing visualization feedback of copper-depletion. Therapeutically, mitochondria-targeted copper-depletion effectively causes mitochondria damage, elevated oxidative stress and reduced ATP production to induce intensive cancer cell death. Moreover, the mesoporous structure enables MSN-TPP/BNA-DPA to deliver doxorubicin to mitochondria for chemotherapy and enhances copper-depletion therapy through H2O2 production. Together, the synergistic therapeutic effect of enhanced copper-depletion therapy and doxorubicin-mediated chemotherapy achieves a remarkable cancer cell-killing effect and significant tumor growth inhibition in 4T1 tumor-bearing mice. This work provides an efficacious strategy for copper-depletion based synergistic cancer therapy.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Animais , Camundongos , Cobre/farmacologia , Peróxido de Hidrogênio/metabolismo , Doxorrubicina , Neoplasias/tratamento farmacológico , Dióxido de Silício/química , Mitocôndrias/metabolismo
10.
ACS Appl Mater Interfaces ; 15(1): 552-565, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36594282

RESUMO

The poor penetration of nanocarriers within tumor dense extracellular matrices (ECM) greatly restricts the access of anticancer drugs to the deep tumor cells, resulting in low therapeutic efficacy. Moreover, the high toxicity of the traditional chemotherapeutics inevitably causes undesirable side effects. Herein, taking the advantages of biosafe H2 and small-sized nanoparticles in diffusion within tumor ECM, we develop a matrix metalloprotease 2 (MMP-2) responsive size-switchable nanoparticle (UAMSN@Gel-PEG) that is composed of ultrasmall amino-modified mesoporous silica nanoparticles (UAMSN) wrapped within a PEG-conjugated gelatin to deliver H2 to the deep part of tumors for effective gas therapy. Ammonia borane (AB) is chosen as the H2 prodrug that can be effectively loaded into UAMSN by hydrogen-bonding adsorption. Gelatin is used as the substrate of MMP-2 to trigger size change and block AB inside UAMSN during blood circulation. PEG is introduced to further increase the particle size and endow the nanoparticle with long blood circulation to achieve effective tumor accumulation via the EPR effect. After accumulation into the tumor site, MMP-2 promptly digests gelatin to expose UAMSN loading AB for deep tumor penetration. Upon stimulation by the acidic tumor microenvironment, AB decomposes into H2 for further intratumor diffusion to achieve effective hydrogen therapy. Consequently, such a simultaneous deep tumor penetration of nanocarriers and H2 results in an evident suppression on tumor growth in a 4T1 tumor-bearing model without any obvious toxicity on normal tissues. Our synthetic nanosystem provides a promising strategy for the development of nanomedicines with enhanced tumor permeability and good biosafety for efficient tumor treatment.


Assuntos
Antineoplásicos , Nanopartículas , Metaloproteinase 2 da Matriz , Doxorrubicina/uso terapêutico , Gelatina , Linhagem Celular Tumoral , Microambiente Tumoral
11.
Front Nutr ; 10: 1232129, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781117

RESUMO

Bioflavonoids are natural polyphenolic secondary metabolites that are medicinal. These compounds possess antitumor, cardioprotective, anti-inflammatory, antimicrobial, antiviral, and anti-psoriasis properties to mention a few. Plant species that contain bioflavonoids should be preserved as such. Also, the bioactivity of the bioflavonoids as neutraceutical compounds is compromised following extraction due to their sensitivity to environmental factors like light, pH, and temperature. In other words, the bioflavonoids' shelf-life is affected. Scientists noticed that bioflavonoids have low solubility properties, poor absorption, and low bioavailability following consumption. Researchers came up with methods to encapsulate bioflavonoids in order to circumvent the challenges above and also to mask the unpleasant order these chemicals may have. Besides, scientists cryopreserve plant species that contain bioflavonoids. In this review, we discuss cryopreservation and bioflavonoid microencapsulation focusing mainly on vitrification, slow freezing, and freeze-drying microencapsulation techniques. In addition, we highlight bioflavonoid extraction techniques, medicinal properties, challenges, and future perspectives of cryopreservation and microencapsulation of bioflavonoids. Regardless of the uniqueness of cryopreservation and microencapsulation as methods to preserve bioflavonoid sources and bioflavonoids' bioactivity, there are challenges reported. Freeze-drying technology is costly. Cryoprotectants damage the integrity of plant cells, to say the least. Researchers are working very hard to overcome these challenges. Encapsulating bioflavonoids via coaxial electrospray and then cryopreserving the micro/nanocapsules produced can be very interesting.

12.
Front Endocrinol (Lausanne) ; 14: 1308341, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38098865

RESUMO

Genistein (GN) has been highly recommended for its medicinal properties like anticancer, antidiabetic, antihyperlipidemic, antiviral, and antioxidant activities among others. Recently, scientists realized that Genistein is an endocrine disruptor. It is an obesogen that interferes with the endocrine system causing obesity through many mechanisms like inducing adipocyte differentiation, lipid accumulation, and transformation of some stem cells into adipocytes (bone marrow mesenchymal stem cells for example) in vitro. Animal studies show that GN upregulates genes associated with adipogenesis like CCAAT/enhancer binding protein alpha (Cebpα), CCAAT/enhancer binding protein beta (Cebpß), and PPARγ. In silico studies reveal a strong binding affinity for estrogen receptors. All these findings were contingent on concentration and tissues. It is beyond dispute that obesity is one of the most frustrating medical conditions under the sun. The pathophysiology of this disease was first attributed to a high-calorie diet and lack of physical activity. However, studies proved that these two factors are not enough to account for obesity in both children and adults. This mini review highlights how Genistein interaction with the peroxisome proliferator-activated receptor gamma protein can cause obesity.


Assuntos
Adipogenia , Genisteína , Animais , Criança , Humanos , Genisteína/farmacologia , Diferenciação Celular , Obesidade
13.
Nanoscale ; 14(4): 1271-1284, 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35006226

RESUMO

Poor tumor penetration is a major obstacle to nanomedicine for achieving effective anticancer therapy. Tumor microenvironment-induced nanomedicine size shrinkage is a promising strategy to overcome the drug penetration barrier across the dense tumor matrix. Herein, we design a size-shrinkable nanocarrier that uses acid as a means of triggering a change in particle size for co-achievement of efficient tumor accumulation followed by deep tumor penetration and rapid clearance from the body. This nanocarrier is constructed from a pH-sensitive lipid layer shell and an ultrasmall amino-functionalized mesoporous silica nanoparticle core capable of loading drugs. After intravenous injection into mice bearing the 4T1 tumor, the nanocarrier with an initial hydrodynamic size of about 33 nm could effectively accumulate at the tumor site through the enhanced permeability and retention effect. Subsequently, in the acidic tumor microenvironment, the lipid layer comprising 9 alkyl-spiropyran (SP-C9) undergoes a volume shrinkage due to the conversion of hydrophobic SP-C9 to amphiphilic 9 alkyl-merocyanine (MC-C9), thus leading to a significant decrease in the entire particle size (hydrodynamic size ∼17 nm) for enhanced intratumoral penetration. Moreover, we find that this size-shrinkable nanocarrier could be rapidly excreted out of the body based on the ICP analysis, significantly reducing biosafety issues. Benefiting from the effective tumor accumulation and penetration of the nanocarrier, the released doxorubicin shows potent antitumor efficacy. This demonstrates the high potential of the designed nanocarrier in solid tumor treatment.


Assuntos
Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Camundongos , Neoplasias/tratamento farmacológico , Dióxido de Silício , Microambiente Tumoral
14.
Biomater Sci ; 10(9): 2358-2369, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35383789

RESUMO

Employing hypoxia-activated prodrugs is an appealing oncotherapy strategy, but limited by insufficient tumor hypoxia. Moreover, a standalone prodrug fails to treat tumors satisfactorily due to tumor complexity. Herein, a nanosystem (TPZ@FeMSN-GOX) was established for triple synergetic cancer starvation therapy, hypoxia-activated chemotherapy and chemodynamic therapy (CDT). TPZ@FeMSN-GOX was prepared by synthesizing iron-doped mesoporous silica nanoparticles (FeMSNs) followed by surface conjugation with glucose oxidase (GOX), and then loading with hypoxia-activated prodrug tirapazamine (TPZ). When TPZ@FeMSN-GOX entered the tumor cells, GOX could not only exhaust glucose to starve cancer cells and concomitantly produce H2O2, but also consume O2 to aggravate the hypoxia environment and amplify TPZ-mediated chemotherapy. Meanwhile, the released Fe3+ was reduced to reactive Fe2+ by endogenous glutathione, which ultimately decomposed the produced H2O2 and endogenous H2O2 into highly toxic ˙OH, guaranteeing highly efficient CDT. Together, TPZ@FeMSN-GOX could effectively kill cancer cells and significantly inhibit tumor growth, providing a good paradigm for effective tumor treatment.


Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Linhagem Celular Tumoral , Glucose , Glucose Oxidase , Humanos , Peróxido de Hidrogênio , Hipóxia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Tirapazamina/farmacologia
15.
Colloids Surf B Biointerfaces ; 216: 112603, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35653958

RESUMO

Peroxidase nanozyme, enabling decomposition of hydrogen peroxide (H2O2) into highly toxic hydroxyl radical (•OH), is an emerging technology for tumor treatment. However, limited by the low H2O2 level in the tumor microenvironment, the standalone peroxidase nanozyme-mediated therapy usually fails to achieve desirable therapeutic outcomes. Herein, we presented a mesoporous nanozyme that not only had peroxidase-like activity but also could deliver anticancer drug for synergistic tumor therapy. The nanozyme, that was, iron-doped mesoporous silica nanoparticle (FeMSN), was prepared by a sol-gel method and then a calcination treatment. The introduction of iron endowed FeMSN with peroxidase-like activity that could decompose H2O2 into •OH under acidic condition for chemodynamic therapy of tumors. Meanwhile, the mesoporous structure enabled FeMSN to deliver anticancer drug doxorubicin (DOX) for chemotherapy and enhanced chemodynamic therapy through H2O2 production, ultimately achieving synergistic effect to improve the efficacy of tumor treatment. The in-vitro and in-vivo results demonstrated that DOX-loaded FeMSN exhibited significant cancer cell-killing effect and potently inhibited tumor growth. Collectively, this study represented a paradigm for achieving efficient tumor therapy through design of peroxidase-like nanozyme with drug delivery capability, which might advance the development of nanozyme in tumor chemodynamic therapy.


Assuntos
Neoplasias , Peroxidase , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Ferro/farmacologia , Neoplasias/terapia , Peroxidases , Microambiente Tumoral
16.
ACS Appl Mater Interfaces ; 14(11): 13122-13135, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35286061

RESUMO

Chemodynamic therapy (CDT) has attracted increasing attention in tumor treatment but is limited by insufficient endogenous H2O2. Moreover, it is challenging for monotherapy to achieve a satisfactory outcome due to tumor complexity. Herein, we developed an intelligent nanoplatform that could respond to a tumor microenvironment to induce efficient CDT without complete dependence on H2O2 and concomitantly generate chemotherapy and oncosis therapy (OT). The nanoplatform was constructed by a calcium- and iron-doped mesoporous silica nanoparticle (CFMSN) loaded with dihydroartemisinin (DHA). After entering into cancer cells, the nanoplatform could directly convert the intracellular H2O2 into toxic •OH due to the Fenton-like activity of CFMSN. Meanwhile, the acidic microenvironment and endogenous chelating molecules triggered Ca2+ and Fe3+ release from the nanoplatform, causing particle collapse with accompanying DHA release for chemotherapy. Simultaneously, the released Ca2+ induced intracellular Ca2+-overloading for OT, which was further enhanced by DHA, while the released Fe3+ was reduced to reactive Fe2+ by intracellular glutathione, guaranteeing efficient Fenton reaction-mediated CDT. Moreover, Fe2+ cleaved the peroxy bonds of DHA to generate C-centered radicals to further amplify CDT. Both in vitro and in vivo results confirmed that the nanoplatform exhibited excellent anticancer efficacy via the synergistic effect of multi therapeutic modalities, which is extremely promising for high-efficient cancer therapy.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Glutationa/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Neoplasias/tratamento farmacológico , Microambiente Tumoral
17.
Int J Pharm ; 594: 120165, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309835

RESUMO

New drugs are frequently found with poor water-solubility in recent pharmaceutical projects, which brings difficulties of bioavailability for the clinical development of new drugs. When these drug compounds in a crystalline state are absorbed by gastrointestinal tract, their dissolution rates and absorption rates are very limited. Nowadays, various methods have been developed to improve the solubility, dissolution and bioavailability of drugs. According to the characteristics of drugs, this work suggests the use of spray drying technology to amorphize APIs (active pharmaceutical ingredients) to improve their bioavailability. This work reviews the properties of the spray-dried amorphous drugs, the progress made in drug synthesis and application, and the existing problems.


Assuntos
Preparações Farmacêuticas , Disponibilidade Biológica , Composição de Medicamentos , Solubilidade
18.
J Nanosci Nanotechnol ; 20(12): 7362-7368, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711602

RESUMO

A defect-related luminescent mesoporous silica nanoparticle (DLMSN) with simultaneous excellent luminescence, high drug loading efficiency and release capacity was prepared upon calcination of 3-aminopropyltriethoxysilane (APTES)-functionalized mesoporous silica nanoparticle (AP-MSN) under a relatively moderate temperature. Under ultraviolet excitation at 365 nm, DLMSN exhibited intense white-blue emission with a range of 400-500 nm, which was inferred to originate from the effective carbon or nitrogen defect in the particle causing by APTES calcination. Additionally, the luminescence intensity of DLMSN was significantly affected by APTES concentration and calcination temperature during the preparation procedure. Within all the tested values, the maximum luminescence intensity was achieved when APTES concentration and calcination temperature were 0.851 mmol and 300 °C, respectively. The drug storage and release tests demonstrated that DLMSN had efficient drug storage and good pH-dependent release for ibuprofen (IBU). Interestingly, ibuprofen-loaded DLMSN (IBU@DLMSN) still exhibit an intense luminescence with an emission peak at around 410 nm under 365 nm excitation, which gradually increased with the sustained release of IBU from IBU@DLMSN. These results suggest that the as-prepared DLMSN may have potential as a detectable nanocarrier in the drug delivery field.


Assuntos
Portadores de Fármacos , Nanopartículas , Luminescência , Porosidade , Dióxido de Silício
19.
Biomater Sci ; 8(12): 3418-3429, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32405634

RESUMO

The balance between tumor accumulation and renal clearance has severely limited the efficacy of mesoporous silica-based drug nanocarriers in cancer therapy. Herein, a pH-responsive dissociable mesoporous silica-based nanoplatform with efficient dual-drug co-delivery, tumor accumulation and rapid clearance for cancer therapy is achieved by adjusting the wetting of the mesoporous silica surface. At pH 7.4, the synthesized spiropyran- and fluorinated silane-modified ultrasmall mesoporous silica nanoparticles (SP-FS-USMSN) self-assemble to form larger nanoclusters (denoted as SP-FS-USMSN cluster) via hydrophobic interactions, which can effectively co-deliver anticancer drugs, doxorubicin hydrochloride (Dox) and curcumin (Cur), based on the mesopores within SP-FS-USMSN and the voids among the stacked SP-FS-USMSN. At pH 4.5-5.5, the conformational conversion of spiropyran from a "closed" state to an "open" state causes the wetting of the SP-FS-USMSN surface, leading to the dissociation of the SP-FS-USMSN cluster for drug release and renal clearance. The in vitro and in vivo studies demonstrate that the Cur and Dox co-loaded SP-FS-USMSN cluster (Cur-Dox/SP-FS-USMSN cluster) possesses great combined cytotoxicity, and can accumulate into tumor tissue by its large size-favored EPR effect and potently suppress tumor growth in HepG2-xenografted mice. This research demonstrates that the SP-FS-USMSN cluster may be a promising drug delivery system for cancer therapy and lays the foundation for practical mesoporous silica-based nanomedicine designs in the future.


Assuntos
Antineoplásicos , Curcumina , Doxorrubicina , Sistemas de Liberação de Medicamentos , Nanopartículas , Dióxido de Silício , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Benzopiranos/administração & dosagem , Benzopiranos/química , Benzopiranos/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Curcumina/química , Curcumina/farmacocinética , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Feminino , Células Hep G2 , Humanos , Indóis/administração & dosagem , Indóis/química , Indóis/farmacocinética , Camundongos Nus , Nanopartículas/administração & dosagem , Nanopartículas/química , Neoplasias/tratamento farmacológico , Nitrocompostos/administração & dosagem , Nitrocompostos/química , Nitrocompostos/farmacocinética , Porosidade , Silanos/administração & dosagem , Silanos/química , Silanos/farmacocinética , Dióxido de Silício/administração & dosagem , Dióxido de Silício/química , Dióxido de Silício/farmacocinética
20.
J Colloid Interface Sci ; 525: 126-135, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29702319

RESUMO

Since adsorption and nanomaterials had been respectively found to be the most promising technique and the preferred adsorbents for heavy metal ions removal, in this study, novel mesoporous silica-calcium phosphate (MS-CP) hybrid nanoparticles were synthesized by a facile one-pot method, and subsequently assessed as adsorbent for Cd2+ removal from aqueous solution. MS-CP were characterized by scanning and transmission electron microscopies, etc. The influences of initial Cd2+ concentration, contact time, solution temperature and solution pH on removal efficiency of Cd2+ were investigated in detail. The results revealed that MS-CP were nanospheres of ∼20 nm and presented a bimodal pore distribution (3.82 nm and 12.40 nm), a high surface area (314.56 m2/g) and a large pore volume (1.21 cm3/g). The Cd2+ removal experiments demonstrated that MS-CP had a high adsorption capacity due to electrostatic interaction between Cd2+ and silanol groups on MS-CP surface, as well as ion-exchange between Cd2+ and calcium in MS-CP. Additionally, removal efficiency of Cd2+ increased with increasing contact time and solution temperature, while decreased as initial Cd2+ concentration increased. The maximum adsorption capacity of Cd2+ by MS-CP was above 153 mg/L. These results suggested that the as-synthesized MS-CP could be promising adsorbent for Cd2+ removal from aqueous solution.

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