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1.
Mater Sci Eng C Mater Biol Appl ; 128: 112311, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474862

RESUMO

Herein, we design a rGO-based magnetic nanocomposite by decorating rGO with citrate-coated magnetic nanoparticles (CMNP). The magnetic rGO (mrGO) was modified by phospholipid-polyethylene glycol to prepare PEGylated mrGO, for conjugating with gastrin-releasing peptide receptor (GRPR)-binding peptide (mrGOG). The anticancer drug doxorubicin (DOX) was bound to mrGO (mrGOG) by π-π stacking for drug delivery triggered by the low pH value in the endosome. The mrGOG showed enhanced photothermal effect under NIR irradiation, endorsing its role for dual targeted DOX delivery. With efficient DOX release in the endosomal environment and heat generation from light absorption in the NIR range, mrGOG/DOX could be used for combination chemo-photothermal therapy after intracellular uptake by cancer cells. We characterized the physico-chemical as well as biological properties of the synthesized nanocomposites. The mrGOG is stable in biological buffer solution, showing high biocompatibility and minimum hemolytic properties. Using U87 glioblastoma cells, we confirmed the magnetic drug targeting effect in vitro for selective cancer cell killing. The peptide ligand-mediated targeted delivery increases the efficiency of intracellular uptake of both nanocomposite and DOX up to ~3 times due to the over-expressed GRPR on U87 surface, leading to higher cytotoxicity. The increased cytotoxicity using mrGOG over mrGO was shown from a decreased IC50 value (0.70 to 0.48 µg/mL) and an increased cell apoptosis rate (19.8% to 47.1%). The IC50 and apoptosis rate changed further to 0.19 µg/mL and 76.8% in combination with NIR laser irradiation, with the photothermal effect supported from upregulation of heat shock protein HSP70 expression. Using U87 tumor xenograft model created in nude mice, we demonstrated that magnetic guidance after intravenous delivery of mrGOG/DOX could significantly reduce tumor size and prolong animal survival over free DOX and non-magnetic guided groups. Augmented with NIR laser treatment for 5 min, the anti-cancer efficacy significantly improves with elevated cell apoptosis and reduced cell proliferation. Together with safety profiles from hematological as well as major organ histological analysis of treated animals, the mrGOG nanocomposite is an effective nanomaterial for combination chemo-photothermal cancer therapy.


Assuntos
Hipertermia Induzida , Nanocompostos , Neoplasias , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Grafite , Fenômenos Magnéticos , Camundongos , Camundongos Nus , Fototerapia , Receptores da Bombesina
2.
Cleft Palate Craniofac J ; : 10556656211026476, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414816

RESUMO

BACKGROUND: Augmentation rhinoplasty with autologous fat grafting is a useful procedure to meet the demand for facial harmonization in the Asian population. We used this procedure during orthognathic surgery to address inadequate dorsum projection. This prospective study was conducted to determine the fat retention rate in patients undergoing simultaneous autologous fat injection augmentation rhinoplasty and orthognathic surgery. METHODS: Nineteen patients were treated with simultaneous bimaxillary orthognathic surgery and autologous fat grafting of the nasal dorsum and tip. The paired t test was used to compare the nasal volumes before and at least 6 months after surgery measured by 3-dimensional computer tomography scans. All measurements were performed twice by the same evaluator at least 2 weeks apart for intrarater consistency. RESULTS: Seventeen patients completed the study. The volume means before and after surgery were 22.3 ± 4.6 cm3 and 23.3 ± 4.7 cm3, respectively, with a mean difference of 1.0 ± 0.3 cm3 (P < .001). The mean retention rate was calculated to be 50.5% ± 7.0% (range: 40.5%-64.7%). Intrarater consistency was high with a Cronbach α of .97 (P < .001) and .98 (P < .001), respectively. CONCLUSION: This prospective study provides objective graft retention measurements for fat injection augmentation rhinoplasty combined with orthognathic surgery. All patients were satisfied with the results and no complications or additional morbidity was noted in the postoperative course. We consider this procedure to be a safe, reliable, and powerful adjunct to improve the aesthetic results of orthognathic surgery.

3.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445516

RESUMO

In this study, we prepared core-sheath nanofiber membranes (CSNFMs) with silver nanoparticles (Ag NPs) embedding in the polylactic acid (PLA) nanofiber sheath and hyaluronic acid (HA) in the nanofiber core. The PLA/Ag NPs sheath provides mechanical support as well as anti-bacterial and anti-inflammatory properties. The controlled release of HA from the core could exert anti-adhesion effects to promote tendon sliding while reducing fibroblast attachment. From the microfibrous structural nature of CSNFMs, they function as barrier membranes to reduce fibroblast penetration without hampering nutrient transports to prevent post-operative peritendinous adhesion. As the anti-adhesion efficacy will depend on release rate of HA from the core as well as Ag NP from the sheath, we fabricated CSNFMs of comparable fiber diameter, but with thick (Tk) or thin (Tn) sheath. Similar CSNFMs with thick (Tk+) and thin (Tn+) sheath but with embedded Ag NPs in the sheath were also prepared. The physico-chemical properties of the barrier membranes were characterized in details, together with their biological response including cell penetration, cell attachment and proliferation, and cytotoxicity. Peritendinous anti-adhesion models in rabbits were used to test the efficacy of CSNFMs as anti-adhesion barriers, from gross observation, histology, and biomechanical tests. Overall, the CSNFM with thin-sheath and Ag NPs (Tn+) shows antibacterial activity with low cytotoxicity, prevents fibroblast penetration, and exerts the highest efficacy in reducing fibroblast attachment in vitro. From in vivo studies, the Tn+ membrane also shows significant improvement in preventing peritendinous adhesions as well as anti-inflammatory efficacy, compared with Tk and Tn CSNFMs and a commercial adhesion barrier film (SurgiWrap®) made from PLA.


Assuntos
Antibacterianos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Poliésteres/química , Prata/química , Traumatismos dos Tendões/tratamento farmacológico , Células 3T3 , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Nanopartículas Metálicas , Camundongos , Testes de Sensibilidade Microbiana , Nanofibras/química , Espectroscopia Fotoeletrônica , Coelhos , Traumatismos dos Tendões/cirurgia , Aderências Teciduais/prevenção & controle
4.
Colloids Surf B Biointerfaces ; 207: 111991, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34333302

RESUMO

Induced pluripotent stem cells (iPSCs) can be used to generate desired types of cells that belong to the three germ layers (i.e., ectoderm, endoderm and mesoderm). These cells possess great potential in regenerative medicine. Before iPSCs are used in various biomedical applications, the existing xenogeneic culture methods must be improved to meet the technical standards of safety, cost effectiveness, and ease of handling. In addition to commonly used 2D substrates, a culture system that mimics the native cellular environment in tissues will be a good choice when culturing iPS cells and differentiating them into different lineages. Hydrogels are potential candidates that recapitulate the native complex three-dimensional microenvironment. They possess mechanical properties similar to those of many soft tissues. Moreover, hydrogels support iPSC adhesion, proliferation and differentiation to various cell types. They are xeno-free and cost-effective. In addition to other substrates, such as mouse embryonic fibroblast (MEF), Matrigel, and vitronectin, the use of hydrogel-based substrates for iPSC culture and differentiation may help generate large numbers of clinical-grade cells that can be used in potential clinical applications. This review mainly focuses on the use of hydrogels for the culture and differentiation of iPSCs into various cell types and their potential applications in regenerative medicine.


Assuntos
Células-Tronco Pluripotentes Induzidas , Animais , Diferenciação Celular , Fibroblastos , Hidrogéis , Camundongos
5.
Cancers (Basel) ; 13(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34359590

RESUMO

As a hydrophobic photosensitizer, IR-780 suffers from poor water solubility and low photostability under near infrared (NIR) light, which severely limits its use during successive NIR laser-assisted photothermal/photodynamic therapy (PTT/PDT). To solve this problem, we fabricate cationic IR-780-loaded liposomes (ILs) by entrapping IR-780 within the lipid bilayer of liposomes. We demonstrate enhanced photostability of IR-780 in ILs with well-preserved photothermal response after three repeated NIR laser exposures, in contrast to the rapid decomposition of free IR-780. The cationic nature of ILs promotes fast endocytosis of liposomal IR-780 by U87MG human glioblastoma cells within 30 min. For PTT/PDT in vitro, ILs treatment plus NIR laser irradiation leads to overexpression of heat shock protein 70 and generation of intracellular reactive oxygen species by U87MG cells, resulting in enhanced cytotoxicity and higher cell apoptosis rate. Using intracranial glioma xenograft in nude mice and administration of ILs by convection enhanced delivery (CED) to overcome blood-brain barrier, liposomal IR-780 could be specifically delivered to the brain tumor, as demonstrated from fluorescence imaging. By providing a highly stable liposomal IR-780, ILs significantly improved anti-cancer efficacy in glioma treatment, as revealed from various diagnostic imaging tools and histological examination. Overall, CED of ILs plus successive laser-assisted PTT/PDT may be an alternative approach for treating brain tumor, which can retard glioma growth and prolong animal survival times from orthotopic brain tumor models.

6.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206318

RESUMO

Photosensitizers (PSs) have received significant attention recently in cancer treatment due to its theranostic capability for imaging and phototherapy. These PSs are highly responsive to light source of a suitable wavelength for image-guided cancer therapy from generated singlet oxygen and/or thermal heat. Various organic dye PSs show tremendous attenuation of tumor cells during cancer treatment. Among them, porphyrin and chlorophyll-based ultraviolet-visible (UV-Vis) dyes are employed for photodynamic therapy (PDT) by reactive oxygen species (ROS) and free radicals generated with 400-700 nm laser lights, which have poor tissue penetration depth. To enhance the efficacy of PDT, other light sources such as red light laser and X-ray have been suggested; nonetheless, it is still a challenging task to improve the light penetration depth for deep tumor treatment. To overcome this deficiency, near infrared (NIR) (700-900 nm) PSs, indocyanine green (ICG), and its derivatives like IR780, IR806 and IR820, have been introduced for imaging and phototherapy. These NIR PSs have been used in various cancer treatment modality by combining photothermal therapy (PTT) and/or PDT with chemotherapy or immunotherapy. In this review, we will focus on the use of different PSs showing photothermal/photodynamic response to UV-Vis or NIR-Vis light. The emphasis is a comprehensive review of recent smart design of PS-loaded nanocomposites for targeted delivery of PSs in light-activated combination cancer therapy.


Assuntos
Nanocompostos/uso terapêutico , Neoplasias/terapia , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Medicina de Precisão , Humanos
7.
Aesthet Surg J ; 41(9): 1003-1010, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34128526

RESUMO

BACKGROUND: Lower blepharoplasty is a common cosmetic operation that relies on minimal postoperative scarring, but Asian patients are at higher risk than Caucasians for hypertrophic and/or widened scars. Botulinum toxin type A (BTX) injections are widely employed to alleviate dynamic facial rhytids and also can improve scar quality by reducing scar tension. The authors assessed whether simultaneous transcutaneous lower blepharoplasty and BTX injections could improve subciliary scar quality. OBJECTIVES: The objective of this study was to assess whether simultaneous transcutaneous lower blepharoplasty and BTX injections could improve subciliary scar quality. METHODS: This is a prospective, randomized, vehicle-controlled, double-blinded clinical trial. Between May 2015 and May 2018, 40 adults who underwent bilateral transcutaneous lower blepharoplasties were randomized to receive BTX (n = 20) or vehicle (normal saline; n = 20) injections into the lateral orbicularis oculi muscle immediately after wound closure. Vancouver Scar Scale, Visual Analogue Scale, and photographic scar width measurements at 3 reference points were recorded at the final clinical follow-up. RESULTS: Thirty-seven patients completed the trial. Vancouver Scar Scale and Visual Analogue Scale scores in the experimental and vehicle control groups were similar, but scar widths in the experimental group at all measured points were significantly narrower than in the vehicle control group (P < 0.001, P = 0.027, and P < 0.001 at each measured point, respectively). CONCLUSIONS: Transcutaneous lower blepharoplasty scars in Asians can be significantly narrowed by simultaneous BTX injections without additional complications.


Assuntos
Blefaroplastia , Toxinas Botulínicas Tipo A , Adulto , Blefaroplastia/efeitos adversos , Cicatriz/etiologia , Cicatriz/prevenção & controle , Humanos , Estudos Prospectivos , Resultado do Tratamento
8.
J Craniofac Surg ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33935145

RESUMO

BACKGROUND: The main objective of contemporary orthognathic surgery is to correct dentofacial deformities. Nonetheless, many adjunct procedures to enhance the esthetic outcome in orthognathic surgical cases have been successfully incorporated to improve patient satisfaction. The authors report our preliminary experience of performing simultaneous orthognathic surgery with Asian double eyelid suture method blepharoplasty in the same surgical setting. METHOD: This case series report includes all 19 consecutive cases presenting to the Chang Gung Craniofacial Center for combined orthognathic surgery with Asian double eyelid suture method blepharoplasty. The double eyelid crease height was measured as the vertical line between the upper eyelid margin (eyelid lash) and the upper eyelid crease, observed at the mid-pupillary line with the eyes in primary gaze. RESULTS: There were no complications or relapse reported within this time period. There was significant improvement in the left and right mid-pupillary double eyelid crease height postsurgery. There were no statistically significant differences between the left and right mid-pupillary double eyelid crease heights after surgery indicating good eyelid crease height symmetry bilaterally was obtained. CONCLUSIONS: Orthognathic surgery combined with suture method blepharoplasty can be safely performed in the same surgical setting without inappropriate rise in costs or operating room time. This case series demonstrates that excellent esthetic results can be obtained in simultaneous bimaxillary orthognathic surgery with suture method Asian blepharoplasty.

9.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804239

RESUMO

Cancer is one of the deadliest diseases in human history with extremely poor prognosis. Although many traditional therapeutic modalities-such as surgery, chemotherapy, and radiation therapy-have proved to be successful in inhibiting the growth of tumor cells, their side effects may vastly limited the actual benefits and patient acceptance. In this context, a nanomedicine approach for cancer therapy using functionalized nanomaterial has been gaining ground recently. Considering the ability to carry various anticancer drugs and to act as a photothermal agent, the use of carbon-based nanomaterials for cancer therapy has advanced rapidly. Within those nanomaterials, reduced graphene oxide (rGO), a graphene family 2D carbon nanomaterial, emerged as a good candidate for cancer photothermal therapy due to its excellent photothermal conversion in the near infrared range, large specific surface area for drug loading, as well as functional groups for functionalization with molecules such as photosensitizers, siRNA, ligands, etc. By unique design, multifunctional nanosystems could be designed based on rGO, which are endowed with promising temperature/pH-dependent drug/gene delivery abilities for multimodal cancer therapy. This could be further augmented by additional advantages offered by functionalized rGO, such as high biocompatibility, targeted delivery, and enhanced photothermal effects. Herewith, we first provide an overview of the most effective reducing agents for rGO synthesis via chemical reduction. This was followed by in-depth review of application of functionalized rGO in different cancer treatment modalities such as chemotherapy, photothermal therapy and/or photodynamic therapy, gene therapy, chemotherapy/phototherapy, and photothermal/immunotherapy.


Assuntos
Grafite/uso terapêutico , Nanomedicina/tendências , Nanoestruturas/uso terapêutico , Neoplasias/terapia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Grafite/química , Humanos , Nanoestruturas/química , Neoplasias/patologia , Fotoquimioterapia/métodos , Fototerapia/métodos
10.
Mater Sci Eng C Mater Biol Appl ; 120: 111689, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545851

RESUMO

Curcumin is reported to possess excellent efficacy to treat wounds that exhibit impaired healing. Heparin shows high affinity for many growth factors that are key biological mediators during the wound healing process. In this study, we aimed to prepare wound dressing membranes, for sustained release of an exogenous factor curcumin as well as sequestering endogenous growth factors at the wound site, to promote wound healing in diabetic rats. Toward this end, we prepared aligned curcumin-loaded poly(lactide-co-glycolide) (PLGA) nanofiber membranes (PC NFMs), followed by high density surface grafting of heparin to fabricate PLGA/curcumin (PCH) NFMs. Both PC and PCH NFMs show high tensile strength, low cytotoxicity and suitable water vapor transmission rate for application as wound dressings. Nonetheless, the PCH NFM shows higher curcumin release rate than PC due to enhanced hydrophilicity, which leads to higher cell migration rate and induced oxidative stress protection of HS68 fibroblast cells in vitro. In vivo study indicated the PCH exhibits the fastest wound closure rate among all membranes with accelerated re-epithelization rate, higher angiogenesis rate and more collagen deposition at the wound site. The accelerated and better skin tissue regeneration could be suggested to correlate with the multi-functionality of nanofibers, where grafted heparin attracting and stabilizing the growth factors important for wound healing in situ, together with relieving the high oxidative stress and the inflammatory cascade from released curcumin during diabetic wound healing.


Assuntos
Curcumina , Diabetes Mellitus Experimental , Nanofibras , Animais , Curcumina/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Heparina , Poliglactina 910 , Ratos , Cicatrização
11.
Ann Plast Surg ; 86(3S Suppl 2): S282-S286, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33443880

RESUMO

BACKGROUND: The objective of this trial is to evaluate the flexibility of the cartilaginous component of the cleft nose after diced cartilage rhinoplasty by determining the degree of possible bending in relation to the vertical nasal dorsum axis and to compare with to a control group of the unaffected population. PATIENTS AND METHODS: Fifteen cleft nose patients with diced cartilage rhinoplasty were included in this study, as well as a control group of 15 unaffected individuals. The angle of maximum nasal bending is measured between the basic and maximum bending axis and performed by the same rater twice at least 2 weeks apart to account for intrarater reliability. Study groups were compared with Fisher and independent t test. RESULTS: The maximum bending to the left side was 16.10 ± 5.03 degrees for the study group and 23.95 ± 6.54 degrees for the control group (P = 0.001). The maximum bending to the right side were 16.54 ± 6.73 degrees for the study group and 23.00 ± 8.88 degrees for the control group (P = 0.034). CONCLUSION: Diced cartilage graft injection for dorsal augmentation yields reproducible and esthetically pleasing outcomes with good flexibility and natural feel of the nasal tip. Although there is a significant difference compared with a nonaffected control group in maximum bending capacity, all patients in this study were satisfied with the results.


Assuntos
Doenças Nasais , Rinoplastia , Cartilagem/transplante , Humanos , Nariz/cirurgia , Reprodutibilidade dos Testes
12.
J Mater Sci Mater Med ; 31(11): 102, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33140175

RESUMO

Porous scaffolds of poly(lactide-co-glycolide) (PLGA; 85:15) and nano-hydroxyapatite (nHAP) were prepared by an emulsion-precipitation procedure from uniform PLGA-nHAP spheres (150-250 µm diameter). These spheres were then thermally sintered at 83 °C to porous scaffolds that can serve for bone tissue engineering or for bone substitution. The base materials PLGA and nHAP and the PLGA-nHAP scaffolds were extensively characterized by X-ray powder diffraction, infrared spectroscopy, thermogravimetry, differential scanning calorimetry, and scanning electron microscopy. The scaffold porosity was about 50 vol% as determined by relating mass and volume of the scaffolds, together with the computed density of the solid phase (PLGA-nHAP). The cultivation of HeLa cells demonstrated their high cytocompatibility. In combination with DNA-loaded calcium phosphate nanoparticles, they showed a good activity of gene transfection with enhanced green fluorescent protein (EGFP) as model protein. This is expected enhance bone growth around an implanted scaffold or inside a scaffold for tissue engineering.

13.
Cancers (Basel) ; 12(11)2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33142721

RESUMO

The consistent expression of disialoganglioside GD2 in neuroblastoma tumor cells and its restricted expression in normal tissues open the possibility to use it for molecularly targeted neuroblastoma therapy. On the other hand, immunoliposomes combining antibody-mediated tumor recognition with liposomal delivery of chemotherapeutics have been proved to enhance therapeutic efficacy in brain tumors. Therefore, we develop immunoliposomes (ImmuLipCP) conjugated with anti-GD2 antibody, for targeted co-delivery of CPT-11 and panobinostat in this study. U87MG human glioma cell line and its drug resistant variant (U87DR), which were confirmed to be associated with low and high expression of cell surface GD2, were employed to compare the targeting efficacy. From in vitro cytotoxicity assay, CPT-11 showed synergism drug interaction with panobinostat to support co-delivery of both drugs with ImmuLipCP for targeted synergistic combination chemotherapy. The molecular targeting mechanism was elucidated from intracellular uptake efficacy by confocal microscopy and flow cytometry analysis, where 6-fold increase in liposome and 1.8-fold increase in drug uptake efficiency was found using targeted liposomes. This enhanced intracellular trafficking for drug delivery endows ImmuLipCP with pronounced cytotoxicity toward U87DR cells in vitro, with 1.6-fold increase of apoptosis rate. Using xenograft nude mice model with subcutaneously implanted U87DR cells, we observe similar biodistribution profile but 5.1 times higher accumulation rate of ImmuLip from in vivo imaging system (IVIS) observation of Cy5.5-labelled liposomes. Taking advantage of this highly efficient GD-2 targeting, ImmuLipCP was demonstrated to be an effective cancer treatment modality to significantly enhance the anti-cancer therapeutic efficacy in U87DR tumors, shown from the significant reduced tumor size in and prolonged survival time of experiment animals as well as diminished expression of cell proliferation and enhanced expression of apoptosis marker proteins in tumor section.

14.
Int J Nanomedicine ; 15: 7569-7582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116488

RESUMO

Introduction: Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Taiwan, and radiation therapy combined with or without chemotherapy is its mainstay treatment. Although it is highly sensitive to radiotherapy, local recurrence and distant metastasis remain difficult unsolved problems. In recent years, graphene oxide (GO) has been found to be a promising novel anticancer drug carrier. Here, we present our designed functionalized GO, polyethylene glycol-coated GO (GO-PEG), as a drug carrier, which was loaded with erlotinib and showed promising anticancer effects on NPC cells. Methods: The effects of GO-PEG-erlotinib on the proliferation, migration, and invasion of NPC cells were investigated by WST-8 assay, wound healing assay, and invasion assay, respectively. RNA sequencing was conducted and analyzed to determine the molecular mechanisms by which GO-PEG-erlotinib affects NPC cells. Results: Our results showed that GO-PEG-erlotinib reduced NPC cell viability in a dose-dependent manner and also inhibited the migration and invasion of NPC cells. The RNA sequencing revealed several related molecular mechanisms. Conclusion: GO-PEG-erlotinib effectively suppressed NPC cell proliferation, migration, and invasion, likely by several mechanisms. GO-PEG-erlotinib may be a potential therapeutic agent for treating NPC in the future.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Cloridrato de Erlotinib/administração & dosagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Cloridrato de Erlotinib/farmacocinética , Cloridrato de Erlotinib/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Grafite/química , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Polietilenoglicóis/química
15.
Int J Mol Sci ; 21(19)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987768

RESUMO

Spinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulated that a nanostructured material for controlled delivery of DHA at the lesion site may be well suited for this purpose. Toward this end, we prepare drug-loaded fibrous mats made of core-shell nanofibers by electrospinning, which contained a polylactic acid (PLA) shell for encapsulation of DHA within the core, for delivery of DHA in situ. In vitro study confirmed sustained DHA release from PLA/DHA core-shell nanofiber membrane (CSNM) for up to 36 days, which could significantly increase neurite outgrowth from primary cortical neurons in 3 days. This is supported by the upregulation of brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) neural marker genes from qRT-PCR analysis. Most importantly, the sustained release of DHA could significantly increase the neurite outgrowth length from cortical neuron cells in 7 days when co-cultured with PLA/DHA CSNM, compared with cells cultured with 3 µM DHA. From in vivo study with a SCI model created in rats, implantation of PLA/DHA CSNM could significantly improve neurological functions revealed by behavior assessment in comparison with the control (no treatment) and the PLA CSNM groups. According to histological analysis, PLA/DHA CSNM also effectively reduced neuron loss and increased serotonergic nerve sprouting. Taken together, the PLA/DHA CSNM may provide a nanostructured drug delivery system for DHA and contribute to neuroprotection and promoting neuroplasticity change following SCI.


Assuntos
Ácidos Docosa-Hexaenoicos/uso terapêutico , Crescimento Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Técnicas de Cultura de Células , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Embrião de Mamíferos , Fenômenos Mecânicos , Nanofibras/química , Neurônios/patologia , Poliésteres/química , Ratos , Ratos Sprague-Dawley
16.
Int J Mol Sci ; 21(19)2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32993166

RESUMO

In this study, we aimed to develop a multifunctional drug/gene delivery system for the treatment of glioblastoma multiforme by combining the ligand-mediated active targeting and the pH-triggered drug release features of graphene oxide (GO). Toward this end, we load irinotecan (CPT-11) to cetuximab (CET)-conjugated GO (GO-CET/CPT11) for pH-responsive drug release after endocytosis by epidermal growth factor receptor (EGFR) over-expressed U87 human glioblastoma cells. The ultimate injectable drug/gene delivery system was designed by co-entrapping stomatin-like protein 2 (SLP2) short hairpin RNA (shRNA) and GO-CET/CPT11 in thermosensitive chitosan-g-poly(N-isopropylacrylamide) (CPN) polymer solution, which offers a hydrogel depot for localized, sustained delivery of the therapeutics after the in situ formation of CPN@GO-CET/CPT11@shRNA hydrogel. An optimal drug formulation was achieved by considering both the loading efficiency and loading content of CPT-11 on GO-CET. A sustained and controlled release behavior was found for CPT-11 and shRNA from CPN hydrogel. Confocal microscopy analysis confirmed the intracellular trafficking for the targeted delivery of CPT-11 through interactions of CET with EGFR on the U87 cell surface. The efficient transfection of U87 using SLP2 shRNA was achieved using CPN as a delivery milieu, possibly by the formation of shRNA/CPN polyplex after hydrogel degradation. In vitro cell culture experiments confirmed cell apoptosis induced by CPT-11 released from acid organelles in the cytoplasm by flow cytometry, as well as reduced SLP2 protein expression and inhibited cell migration due to gene silencing. Finally, in vivo therapeutic efficacy was demonstrated using the xenograft of U87 tumor-bearing nude mice through non-invasive intratumoral delivery of CPN@GO-CET/CPT11@shRNA by injection. Overall, we have demonstrated the novelty of this thermosensitive hydrogel to be an excellent depot for the co-delivery of anticancer drugs and siRNA. The in situ forming hydrogel will not only provide extended drug release but also combine the advantages offered by the chitosan-based copolymer structure for siRNA delivery to broaden treatment modalities in cancer therapy.


Assuntos
Proteínas Sanguíneas , Quitosana , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Glioblastoma , Grafite , Irinotecano , Proteínas de Membrana , Proteínas de Neoplasias , RNA Interferente Pequeno , Proteínas Sanguíneas/antagonistas & inibidores , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Linhagem Celular Tumoral , Quitosana/química , Quitosana/farmacologia , Receptores ErbB/agonistas , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/terapia , Grafite/química , Grafite/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Irinotecano/química , Irinotecano/farmacologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia
17.
ACS Appl Mater Interfaces ; 12(36): 40141-40152, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32845120

RESUMO

Understanding the molecular mechanisms of graphene oxide (GO)-based biomaterials is important for logical biomedical applications. Previous studies have revealed biointeractions between GO and immune effector cells, but the effects on neutrophils, crucial cells in the immune system, have not been thoroughly discussed. In this study, GO nanoformulations were synthesized with different functional groups, including GO, GO-carboxylated (GO-COOH), and PEGylated GO (GO-PEG), with different surface features, which were elucidated using imaging methods and surface-sensitive quantitative spectroscopic techniques, including atomic force microscopy (AFM), transmission electron microscopy (TEM), and X-ray photoemission spectroscopy (XPS). The GO-based nanoformulations elicited reactive oxygen species (ROS) generation and neutrophil extracellular trap (NET) formation in human neutrophils. Nanoformulated GO stimulates NET development via the formation of ROS. An endocytosis study revealed that nanoformulated GO facilitated internalization by neutrophils via macropinocytosis and actin-dependent phagocytosis. Importantly, calcium mobilization and phosphorylation proteins such as mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38) and AKT were involved in the activation of neutrophils. These findings offer the first verification that nanoformulated GO exhibits direct effects on human neutrophils.


Assuntos
Materiais Biocompatíveis/farmacologia , Grafite/farmacologia , Nanopartículas/química , Neutrófilos/efeitos dos fármacos , Adulto , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Antígeno CD11b/biossíntese , Grafite/síntese química , Grafite/química , Humanos , Ativação de Neutrófilo/efeitos dos fármacos , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Tamanho da Partícula , Espécies Reativas de Oxigênio/imunologia , Propriedades de Superfície , Adulto Jovem
18.
Int J Mol Sci ; 21(15)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32707876

RESUMO

In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized magnetic liposomes (MLs) for simultaneous magnetic hyperthermia (MH) in the presence of AMF and photothermia (PT) induced by NIR laser exposure, which amplified the heating efficiency for dual-mode cancer cell killing and tumor therapy. Since the heating capability is directly related to the amount of entrapped CMNPs in MLs, while the liposome size is important to allow internalization by cancer cells, response surface methodology was utilized to optimize the preparation of MLs by simultaneously maximizing the encapsulation efficiency (EE) of CMNPs in MLs and minimizing the size of MLs. The experimental design was performed based on the central composite rotatable design. The accuracy of the model was verified from the validation experiments, providing a simple and effective method for fabricating the best MLs, with an EE of 87% and liposome size of 121 nm. The CMNPs and the optimized MLs were fully characterized from chemical and physical perspectives. In the presence of dual AMF and NIR laser treatment, a suspension of MLs demonstrated amplified heat generation from dual hyperthermia (MH)-photothermia (PT) in comparison with single MH or PT. In vitro cell culture experiments confirmed the efficient cellular uptake of the MLs from confocal laser scanning microscopy due to passive accumulation in human glioblastoma U87 cells originated from the cationic nature of MLs. The inducible thermal effects mediated by MLs after endocytosis also led to enhanced cytotoxicity and cumulative cell death of cancer cells in the presence of AMF-NIR lasers. This functional nanocomposite will be a potential candidate for bimodal MH-PT dual magneto-photothermal cancer therapy.


Assuntos
Glioblastoma/tratamento farmacológico , Hipertermia Induzida/métodos , Lipossomos/química , Nanopartículas de Magnetita/química , Nanocompostos/química , Fototerapia/métodos , Células 3T3 , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ácido Cítrico/química , Endocitose/efeitos dos fármacos , Glioblastoma/radioterapia , Humanos , Hipertermia , Hipertermia Induzida/instrumentação , Lasers , Lipossomos/síntese química , Lipossomos/ultraestrutura , Campos Magnéticos , Nanopartículas de Magnetita/efeitos da radiação , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Microscopia Eletrônica de Transmissão , Nanocompostos/efeitos da radiação , Tamanho da Partícula
19.
Int J Mol Sci ; 21(8)2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32294917

RESUMO

Recombinant tissue plasminogen activator (rtPA) is the only thrombolytic agent that has been approved by the FDA for treatment of ischemic stroke. However, a high dose intravenous infusion is required to maintain effective drug concentration, owing to the short half-life of the thrombolytic drug, whereas a momentous limitation is the risk of bleeding. We envision a dual targeted strategy for rtPA delivery will be feasible to minimize the required dose of rtPA for treatment. For this purpose, rtPA and fibrin-avid peptide were co-immobilized to poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (PMNP) to prepare peptide/rtPA conjugated PMNPs (pPMNP-rtPA). During preparation, PMNP was first surface modified with avidin, which could interact with biotin. This is followed by binding PMNP-avidin with biotin-PEG-rtPA (or biotin-PEG-peptide), which was prepared beforehand by binding rtPA (or peptide) to biotin-PEG-maleimide while using click chemistry between maleimide and the single -SH group in rtPA (or peptide). The physicochemical property characterization indicated the successful preparation of the magnetic nanoparticles with full retention of rtPA fibrinolysis activity, while biological response studies underlined the high biocompatibility of all magnetic nanoparticles from cytotoxicity and hemolysis assays in vitro. The magnetic guidance and fibrin binding effects were also confirmed, which led to a higher thrombolysis rate in vitro using PMNP-rtPA or pPMNP-rtPA when compared to free rtPA after static or dynamic incubation with blood clots. Using pressure-dependent clot lysis model in a flow system, dual targeted pPMNP-rtPA could reduce the clot lysis time for reperfusion by 40% when compared to free rtPA at the same drug dosage. From in vivo targeted thrombolysis in a rat embolic model, pPMNP-rtPA was used at 20% of free rtPA dosage to restore the iliac blood flow in vascular thrombus that was created by injecting a blood clot to the hind limb area.


Assuntos
Portadores de Fármacos/química , Fibrinolíticos/química , Fibrinolíticos/farmacologia , Nanopartículas de Magnetita/química , Peptídeos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ativador de Plasminogênio Tecidual/administração & dosagem , Animais , Avidina/química , Fenômenos Químicos , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos , Embolia/tratamento farmacológico , Embolia/etiologia , Fibrinólise/efeitos dos fármacos , Ratos , Proteínas Recombinantes/administração & dosagem , Análise Espectral , Nanomedicina Teranóstica , Termogravimetria , Terapia Trombolítica/métodos , Trombose/tratamento farmacológico
20.
Plast Reconstr Surg ; 145(3): 775-779, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32097325

RESUMO

BACKGROUND: Since 2012, the senior author has incorporated the natural curvature of rib cartilage as an alar rim graft in addition to the diced cartilage technique for unilateral cleft rhinoplasty. The aim of this study is to describe this modification and evaluate its long-term results regarding nasal symmetry using three-dimensional stereophotogrammetric assessment (3dMDface system). METHODS: From 2012 to 2018, 47 consecutive patients that underwent secondary unilateral cleft rhinoplasty were reviewed retrospectively. Sixteen patients with both preoperative and postoperative three-dimensional photographs taken at least 6 months after the operation were included. SimPlant O&O software was used to measure parameters on three-dimensional photographs: nostril heights, nostril widths, nasal dorsum heights, alare width, nostril areas, overlapping nostril area, nasal tip protrusion, nasal length, and nasal height before and after surgery. The ratios between cleft and noncleft sides were calculated. In addition, the overlapping nostril area ratio, tip protrusion-width index, and nasal index were compared before and after surgery. RESULTS: The preoperative nostril height ratio (0.79), nostril width ratio (1.24), and nasal dome height ratio (0.84) between cleft and noncleft sides were significantly improved after surgery to 0.93, 1.06, and 0.97, respectively. The preoperative overlapping nostril area ratio (72.33 percent), nasal tip protrusion-width index (0.48), and nasal index (0.81) also showed significant improvement postoperatively to 83.91 percent, 0.57, and 0.74, respectively. CONCLUSION: This preliminary study supports the use of natural curvature of rib cartilage as alar rim graft in secondary unilateral cleft rhinoplasty, with long-term improvement regarding nasal symmetry and nasal profile. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Fenda Labial/cirurgia , Cartilagem Costal/transplante , Cartilagens Nasais/cirurgia , Reoperação/métodos , Rinoplastia/métodos , Feminino , Humanos , Masculino , Cartilagens Nasais/anatomia & histologia , Estudos Retrospectivos , Costelas , Transplante Autólogo/métodos , Resultado do Tratamento , Adulto Jovem
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