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1.
Bioeng Transl Med ; 9(2): e10635, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435829

RESUMO

The prognosis for postinjury peripheral nerve regeneration remains suboptimal. Although transplantation of exogenous Schwann cells (SCs) has been considered a promising treatment to promote nerve repair, this strategy has been hampered in practice by the limited availability of SC sources and an insufficient postengraftment cell retention rate. In this study, to address these challenges, SCs were aggregated into spheroids before being delivered to an injured rat sciatic nerve. We found that the three-dimensional aggregation of SCs induced their acquisition of a repair phenotype, as indicated by enhanced levels of c-Jun expression/activation and decreased expression of myelin sheath protein. Furthermore, our in vitro results demonstrated the superior potential of the SC spheroid-derived secretome in promoting neurite outgrowth of dorsal root ganglion neurons, enhancing the proliferation and migration of endogenous SCs, and recruiting macrophages. Moreover, transplantation of SC spheroids into rats after sciatic nerve transection effectively increased the postinjury nerve structure restoration and motor functional recovery rates, demonstrating the therapeutic potential of SC spheroids. In summary, transplantation of preassembled SC spheroids may hold great potential for enhancing the cell delivery efficiency and the resultant therapeutic outcome, thereby improving SC-based transplantation approaches for promoting peripheral nerve regeneration.

2.
Chembiochem ; 25(3): e202300744, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38055188

RESUMO

Hirudins, natural sulfo(glyco)proteins, are clinical anticoagulants that directly inhibit thrombin, a key coagulation factor. Their potent thrombin inhibition primarily results from antagonistic interactions with both the catalytic and non-catalytic sites of thrombin. Hirudins often feature sulfate moieties on Tyr residues in their anionic C-terminus region, enabling strong interactions with thrombin exosite-I and effectively blocking its engagement with fibrinogen. Although sulfotyrosines have been identified in various hirudin variants, the precise relationship between sulfotyrosine and the number of negatively charged amino acids within the anionic-rich C-terminus peptide domain for the binding of thrombin has remained elusive. By using Fmoc-SPPS, hirudin dodecapeptides homologous to the C-terminus of hirudin variants from various leech species were successfully synthesized, and the effect of sulfotyrosine and the number of negatively charged amino acids on hirudin-thrombin interactions was investigated. Our findings did not reveal any synergistic effect between an increasing number of sulfotyrosines or negatively charged amino acids and their inhibitory activity on thrombin or fibrinolysis in the assays, despite a higher binding level toward thrombin in the sulfated dodecapeptide Hnip_Hirudin was observed in SPR analysis.


Assuntos
Hirudinas , Trombina , Tirosina/análogos & derivados , Hirudinas/farmacologia , Hirudinas/química , Hirudinas/metabolismo , Aminoácidos , Peptídeos/farmacologia , Sítios de Ligação
3.
Int J Biol Macromol ; 256(Pt 1): 128091, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37981271

RESUMO

Bone regeneration is a critical and intricate process vital for healing fractures, defects, and injuries. Although conventional bone grafts are commonly used, they may fall short of optimal outcomes, thereby driving the need for alternative therapies. This research endeavors to explore synergistically designed Hyalo Glass Gel (HGG), and its explicitly for bone tissue engineering and regenerative medicine. The HGG composite comprises a modifiable calcium-based bioactive phosphosilicates-incorporated/crosslinked gelatin-hyaluronic scaffold showcasing promising functional characteristics. The study underscores the distinct attributes of each constituent (gelatin (Gel), hyaluronic acid (HA), and 45S5 calcium sodium phosphosilicates (BG)), and their cooperative influences on the scaffold's performance. Careful manipulation of crosslinking methods facilitates customization of HGG's mechanical attributes, degradation kinetics, and structural features, aligning them with the requisites of bone tissue engineering applications. Moreover, the integration of BG augments the scaffold's bioactivity, thereby expediting tissue regenerative processes. This comprehensive evaluation encompasses HGG's physicochemical aspects, mechanical traits rooted in viscoelasticity, as well as its biodegradability, in-vitro bioactivity, and interactions with stem cells. The result obtained underscores the viscoelastic nature of HGG, substantiating its capacity to foster mesenchymal stem cell viability, proliferation, and differentiation. Significantly, HGG manifests biocompatibility and adjustable attributes, exhibits pronounced drug (vancomycin) retention abilities, rendering it apt for wound healing, drug delivery, and bone regeneration. Its distinctive composition, tailored attributes, and mimicry of bone tissue's extracellular matrix (ECM) due to its bioactive nature, collectively situate its potential as a versatile biomaterial for subsequent research and development endeavors with compelling prospects in bone tissue engineering and regenerative medicine.


Assuntos
Gelatina , Hidrogéis , Hidrogéis/farmacologia , Hidrogéis/química , Gelatina/farmacologia , Gelatina/química , Cálcio , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Regeneração Óssea , Tecidos Suporte
4.
Mater Today Bio ; 23: 100876, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38089433

RESUMO

A new approach to treating vascular blockages has been developed to overcome the limitations of current thrombolytic therapies. This approach involves biosafety and multimodal plasma-derived theranostic platelet vesicle incorporating iron oxide constructed nano-propellers platformed technology that possesses fluorescent and magnetic features and manifold thrombus targeting modes. The platform is capable of being guided and visualized remotely to specifically target thrombi, and it can be activated using near-infrared phototherapy along with an actuated magnet for magnetotherapy. In a murine model of thrombus lesion, this proposed multimodal approach showed an approximately 80 % reduction in thrombus residues. Moreover, the new strategy not only improves thrombolysis but also boosts the rate of lysis, making it a promising candidate for time-sensitive thrombolytic therapy.

5.
Int J Nanomedicine ; 18: 5607-5623, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37814664

RESUMO

Due to their non-toxic function in biological systems, Iron oxide NPs (IO-NPs) are very attractive in biomedical applications. The magnetic properties of IO-NPs enable a variety of biomedical applications. We evaluated the usage of IO-NPs for anticancer effects. This paper lists the applications of IO-NPs in general and the clinical targeting of IO-NPs. The application of IONPs along with photothermal therapy (PTT), photodynamic therapy (PDT), and magnetic hyperthermia therapy (MHT) is highlighted in this review's explanation for cancer treatment strategies. The review's study shows that IO-NPs play a beneficial role in biological activity because of their biocompatibility, biodegradability, simplicity of production, and hybrid NPs forms with IO-NPs. In this review, we have briefly discussed cancer therapy and hyperthermia and NPs used in PTT, PDT, and MHT. IO-NPs have a particular effect on cancer therapy when combined with PTT, PDT, and MHT were the key topics of the review and were covered in depth. The IO-NPs formulations may be uniquely specialized in cancer treatments with PTT, PDT, and MHT, according to this review investigation.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Fotoquimioterapia , Compostos Férricos , Fenômenos Magnéticos , Neoplasias/tratamento farmacológico
6.
J Nanobiotechnology ; 21(1): 318, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667248

RESUMO

Impaired wound healing is a significant complication of diabetes. Platelet-derived extracellular vesicles (pEVs), rich in growth factors and cytokines, show promise as a powerful biotherapy to modulate cellular proliferation, angiogenesis, immunomodulation, and inflammation. For practical home-based wound therapy, however, pEVs should be incorporated into wound bandages with careful attention to delivery strategies. In this work, a gelatin-alginate hydrogel (GelAlg) loaded with reduced graphene oxide (rGO) was fabricated, and its potential as a diabetic wound dressing was investigated. The GelAlg@rGO-pEV gel exhibited excellent mechanical stability and biocompatibility in vitro, with promising macrophage polarization and reactive oxygen species (ROS)-scavenging capability. In vitro cell migration experiments were complemented by in vivo investigations using a streptozotocin-induced diabetic rat wound model. When exposed to near-infrared light at 2 W cm- 2, the GelAlg@rGO-pEV hydrogel effectively decreased the expression of inflammatory biomarkers, regulated immune response, promoted angiogenesis, and enhanced diabetic wound healing. Interestingly, the GelAlg@rGO-pEV hydrogel also increased the expression of heat shock proteins involved in cellular protective pathways. These findings suggest that the engineered GelAlg@rGO-pEV hydrogel has the potential to serve as a wound dressing that can modulate immune responses, inflammation, angiogenesis, and follicle regeneration in diabetic wounds, potentially leading to accelerated healing of chronic wounds.


Assuntos
Plaquetas , Complicações do Diabetes , Vesículas Extracelulares , Cicatrização , Plaquetas/química , Vesículas Extracelulares/química , Oxirredução , Complicações do Diabetes/tratamento farmacológico , Humanos , Animais , Camundongos , Ratos , Linhagem Celular , Ratos Wistar , Sobrevivência Celular , Espécies Reativas de Oxigênio/metabolismo , Hidrogéis/química
7.
J Biomed Sci ; 30(1): 79, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37704991

RESUMO

Platelets are small anucleated blood cells primarily known for their vital hemostatic role. Allogeneic platelet concentrates (PCs) collected from healthy donors are an essential cellular product transfused by hospitals to control or prevent bleeding in patients affected by thrombocytopenia or platelet dysfunctions. Platelets fulfill additional essential functions in innate and adaptive immunity and inflammation, as well as in wound-healing and tissue-repair mechanisms. Platelets contain mitochondria, lysosomes, dense granules, and alpha-granules, which collectively are a remarkable reservoir of multiple trophic factors, enzymes, and signaling molecules. In addition, platelets are prone to release in the blood circulation a unique set of extracellular vesicles (p-EVs), which carry a rich biomolecular cargo influential in cell-cell communications. The exceptional functional roles played by platelets and p-EVs explain the recent interest in exploring the use of allogeneic PCs as source material to develop new biotherapies that could address needs in cell therapy, regenerative medicine, and targeted drug delivery. Pooled human platelet lysates (HPLs) can be produced from allogeneic PCs that have reached their expiration date and are no longer suitable for transfusion but remain valuable source materials for other applications. These HPLs can substitute for fetal bovine serum as a clinical grade xeno-free supplement of growth media used in the in vitro expansion of human cells for transplantation purposes. The use of expired allogeneic platelet concentrates has opened the way for small-pool or large-pool allogeneic HPLs and HPL-derived p-EVs as biotherapy for ocular surface disorders, wound care and, potentially, neurodegenerative diseases, osteoarthritis, and others. Additionally, allogeneic platelets are now seen as a readily available source of cells and EVs that can be exploited for targeted drug delivery vehicles. This article aims to offer an in-depth update on emerging translational applications of allogeneic platelet biotherapies while also highlighting their advantages and limitations as a clinical modality in regenerative medicine and cell therapies.


Assuntos
Vesículas Extracelulares , Transplante de Células-Tronco Hematopoéticas , Humanos , Medicina Regenerativa , Plaquetas , Terapia Baseada em Transplante de Células e Tecidos
8.
Int J Biol Macromol ; 250: 126105, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37549762

RESUMO

Long-standing administration of disease-modifying antirheumatic drugs confirms their clinical value for managing rheumatoid arthritis (RA). Nevertheless, there are emergent worries over unwanted adverse risks of systemic drug administration. Hence, a novel strategy that can be used in a drug-free manner while diminishing side effects is immediately needed, but challenges persist in the therapy for RA. To this end, herein we conjugated tyramine (TYR) with alginate (ALG) to form ALG-TYR and then treated it for 5 min with oxygen plasma (ALG-TYR + P/5 min). It was shown that the ALG-TYR + P/5 min hydrogel exhibited favorable viscoelastic, morphological, mechanical, biocompatible, and cellular heat-shock protein amplification behaviors. A thorough physical and structural analysis was conducted on the ALG-TYR + P/5 min hydrogel, revealing favorable physical characteristics and uniform porous structural features within the hydrogel. Moreover, ALG-TYR + P/5 min not only effectively inhibited inflammation of RA but also potentially regulated lesion immunity. Once ALG-TYR + P/5 min was intra-articularly administered to joints of rats with zymosan-induced arthritis, we observed that ALG-TYR + P/5 min could ameliorate syndromes of RA joint. This bioinspired and self-restorable ALG-TYR + P/5 min hydrogel can thus serve as a promising system to provide prospective outcomes to potentiate RA therapy.

9.
J Nanobiotechnology ; 21(1): 260, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553670

RESUMO

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.


Assuntos
Nanopartículas , Trombose , Dipiridamol/farmacologia , Nanopartículas/uso terapêutico , Selectina-P , Fototerapia/métodos , Polímeros , Pirróis , Trombose/tratamento farmacológico , Animais
10.
Adv Healthc Mater ; 12(28): e2301504, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37421244

RESUMO

Traditional thrombolytic therapeutics for vascular blockage are affected by their limited penetration into thrombi, associated off-target side effects, and low bioavailability, leading to insufficient thrombolytic efficacy. It is hypothesized that these limitations can be overcome by the precisely controlled and targeted delivery of thrombolytic therapeutics. A theranostic platform is developed that is biocompatible, fluorescent, magnetic, and well-characterized, with multiple targeting modes. This multimodal theranostic system can be remotely visualized and magnetically guided toward thrombi, noninvasively irradiated by near-infrared (NIR) phototherapies, and remotely activated by actuated magnets for additional mechanical therapy. Magnetic guidance can also improve the penetration of nanomedicines into thrombi. In a mouse model of thrombosis, the thrombosis residues are reduced by ≈80% and with no risk of side effects or of secondary embolization. This strategy not only enables the progression of thrombolysis but also accelerates the lysis rate, thereby facilitating its prospective use in time-critical thrombolytic treatment.


Assuntos
Terapia Trombolítica , Trombose , Camundongos , Animais , Medicina de Precisão , Fibrinolíticos/química , Fibrinolíticos/uso terapêutico , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Fenômenos Magnéticos
11.
ACS Appl Mater Interfaces ; 15(27): 32967-32983, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37384742

RESUMO

Due to the mortality associated with thrombosis and its high recurrence rate, there is a need to investigate antithrombotic approaches. Noninvasive site-specific thrombolysis is a current approach being used; however, its usage is characterized by the following limitations: low targeting efficiency, poor ability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms, and risk of thrombus recurrence that is comparable to that of traditional pharmacological thrombolysis agents. Therefore, it is vital to develop an alternative technique that can overcome the aforementioned limitations. To this end, a cotton-ball-shaped platelet (PLT)-mimetic self-assembly framework engineered with a phototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has been developed. This platform is capable of delivering a synthetic peptide derived from hirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors for noninvasive site-specific thrombolysis, effective anticoagulation, and vascular restoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequently rupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability of the P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancing bioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extended circulation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination can significantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultant phototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor-1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLT nanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.


Assuntos
Trombose , Ativador de Plasminogênio Tecidual , Humanos , Ativador de Plasminogênio Tecidual/farmacologia , Biomimética , Distribuição Tecidual , Trombose/tratamento farmacológico , Terapia Trombolítica/métodos
12.
Adv Healthc Mater ; 12(24): e2300682, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37289540

RESUMO

Thrombolytic and antithrombotic therapies are limited by short circulation time and the risk of off-target hemorrhage. Integrating a thrombus-homing strategy with photothermal therapy are proposed to address these limitations. Using glycol chitosan, polypyrrole, iron oxide and heparin, biomimicking GCPIH nanoparticles are developed for targeted thrombus delivery and thrombolysis. The nanoassembly achieves precise delivery of polypyrrole, exhibiting biocompatibility, selective accumulation at multiple thrombus sites, and enhanced thrombolysis through photothermal activation. To simulate targeted thrombolysis, a microfluidic model predicting thrombolysis dynamics in realistic pathological scenarios is designed. Human blood assessments validate the precise homing of GCPIH nanoparticles to activated thrombus microenvironments. Efficient near-infrared phototherapeutic effects are demonstrated at thrombus lesions under physiological flow conditions ex vivo. The combined investigations provide compelling evidence supporting the potential of GCPIH nanoparticles for effective thrombus therapy. The microfluidic model also offers a platform for advanced thrombolytic nanomedicine development.


Assuntos
Nanopartículas , Trombose , Humanos , Polímeros/uso terapêutico , Microfluídica , Pirróis , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Trombose/tratamento farmacológico , Trombose/patologia , Nanopartículas/uso terapêutico , Terapia Trombolítica
13.
Front Bioeng Biotechnol ; 11: 1148446, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36926691

RESUMO

Rapid and low-cost diagnosis of coronavirus disease 2019 (COVID-19) is essential to identify infected subjects, particularly asymptomatic cases, primarily to arrest the spread of the disease through local transmission. Antibody-based chromatographic serological tests, as an alternative to the RT-PCR technique, offer only limited help due to high false positives. We propose to exploit our cholesteric liquid crystal biosensor platform for one-step, wash-free, rapid detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus directly with minimal sample pre-processing. As mentioned above, cholesteric liquid crystals are an effective and innovative approach to healthcare as a rapid test for the diagnosis of COVID-19 and other diseases.

14.
Int J Biol Macromol ; 235: 123821, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36870633

RESUMO

A combination of chemotherapy and chemodynamic therapy (CDT) is being developed to improve the theranostic efficacy and biological safety of current therapies. However, most CDT agents are restricted due to complex issues such as multiple components, low colloidal stability, carrier-associated toxicity, insufficient reactive oxygen species generation, and poor targeting efficacy. To overcome these problems, a novel nanoplatform composed of fucoidan (Fu) and iron oxide (IO) nanoparticles (NPs) was developed to achieve chemotherapy combined with CDT synergistic treatment with a facile self-assembling manner, and the NPs were made up of Fu and IO, in which the Fu was not only used as a potential chemotherapeutic but was also designed to stabilize the IO and target P-selectin-overexpressing lung cancer cells, thereby producing oxidative stress and thus synergizing the CDT efficacy. The Fu-IO NPs exhibited a suitable diameter below 300 nm, which favored their cellular uptake by cancer cells. Microscopic and MRI data confirmed the lung cancer cellular uptake of the NPs due to active Fu targeting. Moreover, Fu-IO NPs induced efficient apoptosis of lung cancer cells, and thus offer significant anti-cancer functions by potential chemotherapeutic-CDT.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Neoplasias , Humanos , Medicina de Precisão , Selectina-P , Linhagem Celular Tumoral , Nanomedicina Teranóstica , Neoplasias/tratamento farmacológico , Estresse Oxidativo , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas Magnéticas de Óxido de Ferro , Nanopartículas/uso terapêutico
15.
Biomed Pharmacother ; 160: 114397, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36796279

RESUMO

As an alternative strategy for cancer treatment, the combination of cancer nanomedicine and immunotherapy is promising with regard to efficacy and safety; however, precise modulation of the activation of antitumor immunity remains challenging. Therefore, the aim of the present study was to describe an intelligent nanocomposite polymer immunomodulator, drug-free polypyrrole-polyethyleneimine nanozyme (PPY-PEI NZ), which responds to the B-cell lymphoma tumor microenvironment, for precision cancer immunotherapy. Earlier engulfment of PPY-PEI NZs in an endocytosis-dependent manner resulted in rapid binding in four different types of B-cell lymphoma cells. The PPY-PEI NZ effectively suppressed B cell colony-like growth in vitro accompanied by cytotoxicity via apoptosis induction. During PPY-PEI NZ-induced cell death, mitochondrial swelling, loss of mitochondrial transmembrane potential (MTP), downregulation of antiapoptotic proteins, and caspase-dependent apoptosis were observed. Deregulated AKT and ERK signaling contributed to glycogen synthase kinase-3-regulated cell apoptosis following deregulation of Mcl-1 and MTP loss. Additionally, PPY-PEI NZs induced lysosomal membrane permeabilization while inhibiting endosomal acidification, partly protecting cells from lysosomal apoptosis. PPY-PEI NZs selectively bound and eliminated exogenous malignant B cells in a mixed culture system with healthy leukocytes ex vivo. While PPY-PEI NZs showed no cytotoxicity in wild-type mice, they provided long-term and efficient inhibition of the growth of B-cell lymphoma-driven nodules in a subcutaneous xenograft model. This study explores a potential PPY-PEI NZ-based anticancer agent against B-cell lymphoma.


Assuntos
Antineoplásicos , Linfoma de Células B , Linfoma , Humanos , Animais , Camundongos , Polietilenoimina/farmacologia , Polímeros , Pirróis , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente Tumoral
17.
Cancers (Basel) ; 14(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36291827

RESUMO

Near-infrared-photothermal therapy (NIR-PTT) is a potential modality for cancer treatment. Directing photothermal effects specifically to cancer cells may enhance the therapeutic index for the best treatment outcome. While epithelial growth factor receptor (EGFR) is commonly overexpressed/genetically altered in human malignancy, it remains unknown whether targeting EGFR with tyrosine kinase inhibitor (TKI)-conjugated nanoparticles may direct NIR-PTT to cancers with cellular precision. In the present study, we tested this possibility through the fabrication of a polypyrrole-iron oxide-afatinib nanocomposite (PIA-NC). In the PIA-NC, a biocompatible and photothermally conductive polymer (polypyrrole) was conjugated to a TKI (afatinib) that binds to overexpressed wild-type EGFR without overt cytotoxicity. A Fenton catalyst (iron oxide) was further encapsulated in the NC to drive the intracellular ROS surge upon heat activation. Diverse physical and chemical characterization experiments were conducted. Particle internalization, cytotoxicity, ROS production, and apoptosis in EGFR-positive and -negative cell lines were investigated in the presence and absence of NIR. We found that the PIA-NCs were stable with a size of 243 nm and a zeta potential of +35 mV. These PIA-NCs were readily internalized close to the cell membrane by all types of cells used in the study. The Fourier transform infrared spectra showed 3295 cm-1 peaks; substantial O-H stretching was seen, with significant C=C stretching at 1637 cm-1; and a modest appearance of C-O-H bending at 1444 cm-1 confirmed the chemical conjugation of afatinib but not iron oxide to the NC. At a NIR-PTT energy level that has a minimal cytotoxic effect, PIA-NC significantly sensitizes EGFR-overexpressing A549 lung cancer cells to NIR-PTT-induced cytotoxicity at a rate of 70%, but in EGFR-negative 3T3 fibroblasts the rate was 30%. Within 1 min of NIR-PTT, a surge of intracellular ROS was found in PIA-NC-treated A549 cells. This was followed by early induction of cellular apoptosis for 54 ± 0.081% of A549 cells. The number of viable cells was less than a quarter of a percent. Viability levels of A549 cells that had been treated with NIR or PIA were only 50 ± 0.216% and 80 ± 0.216%, respectively. Only 10 ± 0.816% of NIH3T3 cells had undergone necrosis, meaning that 90 ± 0.124% were alive. Viability levels were 65 ± 0.081% and 81 ± 0.2%, respectively, when only NIR and PIA were used. PIA binding was effective against A549 cells but not against NIH3T3 cells. The outcome revealed that higher levels of NC + NIR exposure caused cancer cells to produce more ROS. In summary, our findings proved that a molecularly targeted NC provides an orchestrated platform for cancer cell-specific delivery of NIR-PTT. The geometric proximity design indicates a novel approach to minimizing the off-target biological effects of NIR-PTT. The potential of PIA-NC to be further developed into real-world application warrants further investigation.

18.
Macromol Biosci ; 22(12): e2200288, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36106681

RESUMO

In the fields of biomedicine and tissue engineering, natural polymer-based tissue-engineered scaffolds are used in multiple applications. As a plant-derived polymer, soy protein, containing multiple amino acids, is structurally similar to components of the extra-cellular matrix (ECM) of tissues. It is biological safety provided a good potential to be material for pure natural scaffolds. Moreover, as a protein, the properties of soy protein can be easily adjusted by modifying the functional groups on it. In addition, by blending soy protein with other synthetic and natural polymers, the mechanical characteristics and bioactive behavior of scaffolds can be facilitated for a variety of bio-applications. In this research, soy protein and polysaccharides tapioca starch are used, and gellan gum to develop a protein-based composite scaffold for cell engineering. The morphology and surface chemical composition are characterized via micro-computed tomography (micro-CT), scanning electron microscope (SEM), and fourier-transform infrared (FTIR) spectroscopy. The soy/tapioca/gellan gum (STG) composite scaffolds selectively help the adhesion and proliferation of L929 fibroblast cells while improving the migration of L929 fibroblast cells in STG composite scaffolds as the increase of soy protein proportion of the scaffold. In addition, STG composite scaffolds show great potential in the wound healing model to enhance rapid epithelialization and tissue granulation.


Assuntos
Manihot , Proteínas de Soja , Proteínas de Soja/farmacologia , Proteínas de Soja/química , Microtomografia por Raio-X , Engenharia Tecidual/métodos , Tecidos Suporte/química , Bandagens , Polímeros/química , Amido/farmacologia
19.
Talanta ; 250: 123698, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35763951

RESUMO

An early diagnosis of acute myocardial infarction (AMI) or thrombosis is complicated in patients with non-diagnostic features. AMI or thrombosis patients with chest pain are unintentionally discharged and have increased mortality. The study aimed to develop a smartphone biomedical sensor as a rapid test for AMI or thrombosis by naked-eye observation. The system was built on dimethyloctadecyl [3-(trimethoxysilyl)propyl]ammonium chloride (DMOAP)-coated glass substrates, which refers to a nematic liquid crystal (LC)-binding antibody. One of the main biomolecules, cardiac troponin I (cTnI), is a substance in blood in people whose bodies are vulnerable to suffering a myocardial infarction or thrombosis. The other medium, LC, is a sensing biomaterial as an earlier detection method of ameliorating the disadvantages of older methods. Results revealed that the density of cTnI was positively correlated with the coefficient of light transmittance, and it has a high chance of being developed as a point-of-care device for a home inspection as it can be operated with a smartphone. As discussed above, the nematic LC is an effective and innovative healthcare method as a rapid test for diagnosis of AMI or thrombosis related diseases by naked-eye observation.


Assuntos
Cristais Líquidos , Infarto do Miocárdio , Cloreto de Amônio , Materiais Biocompatíveis , Biomarcadores , Humanos , Infarto do Miocárdio/diagnóstico , Smartphone , Troponina I
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