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1.
J Robot Surg ; 18(1): 167, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592362

RESUMO

This meta-analysis was conducted to evaluate and contrast the effectiveness of robotic-assisted and laparoscopic colorectal surgery in the treatment of obese patients. In February 2024, we carried out an exhaustive search of key global databases including PubMed, Embase, and Google Scholar, limiting our focus to studies published in English and Chinese. We excluded reviews, protocols lacking published results, articles derived solely from conference abstracts, and studies not relevant to our research objectives. To analyze categorical variables, we utilized the Cochran-Mantel-Haenszel method along with random-effects models, calculating inverse variances and presenting the outcomes as odds ratios (ORs) along with their 95% confidence intervals (CIs). Statistical significance was determined when p values were less than 0.05. In our final meta-analysis, we included eight cohort studies, encompassing a total of 5,004 patients. When comparing the robotic surgery group to the laparoscopic group, the findings revealed that the robotic group experienced a longer operative time (weighted mean difference (WMD) = 37.53 min, 95% (CI) 15.58-59.47; p = 0.0008), a shorter hospital stay (WMD = -0.68 days, 95% CI -1.25 to -0.10; p = 0.02), and reduced blood loss (WMD = -49.23 mL, 95% CI -64.31 to -34.14; p < 0.00001). No significant differences were observed between the two groups regarding overall complications, conversion rates, surgical site infections, readmission rates, lymph node yield, anastomotic leakage, and intestinal obstruction. The results of our study indicate that robot-assisted colorectal surgery offers benefits for obese patients by shortening the length of hospital stay and minimizing blood loss when compared to laparoscopic surgery. Nonetheless, it is associated with longer operation times and shows no significant difference in terms of overall complications, conversion rates, rehospitalization rates, and other similar metrics.


Assuntos
Cirurgia Colorretal , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Obesidade/complicações , Procedimentos Cirúrgicos Robóticos/métodos
2.
Eur J Med Chem ; 267: 116228, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38354521

RESUMO

In quest for new photosensitizers (PSs) with remarkable antitumor photodynamic efficacy, a series of fifteen quaternary ammonium (QA) cations conjugated 5,15-diaryltetranaphtho[2,3]porphyrins (Ar2TNPs) was synthesized and evaluated in vitro and in vivo to understand how variations in the length of the alkoxy group and the kind of QA cations on meso-phenyl influence the photodynamic antitumor activity. All final compounds (I1-5, II1-5, and III1-5) exhibited robust absorption at 729 nm with significant bathochromic shift and high molar extinction coefficients (1.16 × 105-1.41 × 105 M-1 cm-1), as well as other absorptions at 445, 475, 651, and 714 nm for tumors and other diseases of diverse sizes and depths. Upon exposure to 474 nm light, they displayed intense fluorescence emission with fluorescence quantum yields ranging from 0.32 to 0.43. The ability to generate reactive oxygen species (ROS) was also quantified, attaining a maximum rate of up to 0.0961 s-1. The IC50 values of all the compounds regarding phototoxicity and dark toxicity were determined using KYSE-150 cells, and the phototoxicity indices were calculated. Among these compounds, III1 demonstrated the highest phototoxic index with minimal dark toxicity, and suppressed successfully the growth of esophageal carcinoma xenograft with favorable tolerance in vivo. Furthermore, the histological results showed III1-mediated PDT had a significant cytotoxic effect on the tumor. These outcomes underscore the potential of III1 as a highly effective antitumor photosensitizer drug in photodynamic therapy (PDT).


Assuntos
Compostos de Amônio , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Porfirinas/farmacologia , Cátions
3.
Bioorg Chem ; 143: 107097, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190797

RESUMO

To discover new photosensitizers with long wavelength UV-visible absorption, high efficiency, and low side effects for photodynamic therapy, here, a series of novel thieno[3,2-b]thiophene-fused BODIPY derivatives were designed, synthesized and characterized. These compounds had a distinct absorption band at 640-680 nm, fluorescence emission at 650-760 nm, and good solubility with anti-aggregation effects. These new compounds possessed obvious singlet oxygen generation ability and photodynamic anti-Eca-109 cancer cells activities in vitro. Among them, compound II4 could be well uptaked by Eca-109 cells, and result in the apoptosis after laser irradiation, and have outstanding photodynamic efficiency both in vitro and in vivo. Therefore, II4 could be considered as a potential photosensitizer drug candidate for PDT and photo-imaging.


Assuntos
Compostos de Boro , Fotoquimioterapia , Fotoquimioterapia/métodos , Solubilidade , Tiofenos/farmacologia , Fármacos Fotossensibilizantes/farmacologia
5.
Eur J Med Chem ; 264: 115980, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38039789

RESUMO

In the pursuit of new potent photosensitizers (PSs) for photodynamic therapy (PDT) with better efficacy, a series of 5,15-diaryltetranaphtho [2,3]porphyrins (Ar2TNPs) with two or four carboxyalkoxy groups were designed, synthesized, and evaluated. These new compounds exhibited strong, broad and red-shifted UV-vis absorptions at 729 nm and other strong absorptions at 446, 475, 650, 659, 714 nm for tumors and other diseases of varying sizes and depths. They possess high molar extinction coefficients (0.95 × 105-1.48 × 105 M-1 cm-1), good singlet oxygen quantum yields and photodynamic antitumor effects towards Eca-109 cells in vitro. It is suggested that the extension of porphyrin with naphthalene into Ar2TNP results into remarkable improvement of photophysical characteristics, while the introduction of carboxyalkoxy groups on meso-phenyl can significantly improve the solubility and photodynamic effects in vitro and in vivo. Notably, compound II3 can localize primarily in lysosomes of Eca-109 cells and induce substantial cell apoptosis after PDT. It can also selectively accumulate in tumor tissues and be traced real-timely through in vivo fluorescence imaging with distinctive inhibition of tumor growth. Therefore, compound II3 deserves to be considered as a promising PDT drug candidate for individualized tumor real-time tracing and treatment.


Assuntos
Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Porfirinas/farmacologia , Apoptose
6.
Eur J Med Chem ; 264: 116012, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056302

RESUMO

The discovery of new photosensitizer drugs with long wavelength Uv-vis absorption, high efficiency and low side-effects is still a challenge in photodynamic therapy. Here a series of novel meso-substitutedphenyl thieno[3,2-b]thiophene-fused BODIPY derivatives were designed, synthesized and characterized. All these compounds have strong absorption at 640-680 nm and obvious fluorescence emission at 650-760 nm. They exhibited high singlet oxygen generation ability and significant photodynamic efficiency against Eca-109 cancer cells. Compounds II4, II6, II9, II10 and II13 could generate intracellular ROS and induce cell apoptosis after laser irradiation, which displayed superior photodynamic efficiency against Eca-109 cells than Temoporfin in vitro and in vivo. Among them, compound II4 specifically exhibited excellent anti-tumor efficacy, and could be selected as a new drug candidate for PDT.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/farmacologia , Tiofenos/farmacologia , Compostos de Boro/farmacologia , Oxigênio Singlete
7.
Nanomedicine (Lond) ; 19(2): 127-143, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38131290

RESUMO

Background: Photodynamic therapy (PDT) of cancer has been limited by the poor solubility of most photosensitizers, use of high drug dosages, and the pH difference between the tumor tissue microenvironment (slightly acidic) and the bloodstream. These affect cellular uptake, selectivity and singlet oxygen generation. Materials & methods: We formulated Photinia glabra-green synthesized zinc oxide-protoporphyrin IX (PG-ZnO-PP) nanoconjugates by conjugating the ZnO nanoparticles enriched with amino groups and PP. Results: PG-ZnO-PP nanoconjugates showed higher rate of reactive oxygen species generation, improved cellular uptake in the acidic pH and lower IC50 toward Eca-109 cells for PDT. Conclusion: PG-ZnO-PP nanoconjugates are a potential solution to reducing drug dosage of PP through improved drug uptake, for enhanced targetability and reduced skin photosensitivity with improved PDT efficacy.


The progress of treating cancer using light-sensitive drugs and laser light of known wavelength has been limited by the poor solubility of most light-sensitive drugs, the use of high drug dosages and the slightly acidic environment within the cancerous tissues compared with normal blood in the body. These affect the ability of drugs to accumulate in cancerous cells, and not the normal cells, and the ability to produce the oxygen species that are toxic to the cancerous cells. In this paper, we prepared nanoparticles from zinc acetate using Photinia glabra (PG) fruit extract which were then used to chemically react with a light-sensitive drug called protoporphyrin IX (PP) to formulate small particles known as PG­zinc oxide (ZnO)­PP nanoconjugates. Our results showed that PG­ZnO­PP nanoconjugates had the ability to produce the toxic oxygen particles at a high rate and in good quantity. They also had a higher capability to accumulate in the cancerous cells at a pH below 7 with lower values of the drug needed to cause 50% of cell death toward the cancerous cells which affect the tube that connects from the throat to the stomach when projected with laser light. We could consider PG­ZnO­PP nanoconjugates to serve as a potential solution for reducing the dosage of PP needed to treat cancer in the presence of laser light, and at the same time they can help to reduce the skin-related side effects for patients after treatment when exposed to light.


Assuntos
Neoplasias , Photinia , Fotoquimioterapia , Protoporfirinas , Óxido de Zinco , Nanoconjugados , Óxidos , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico
8.
Risk Manag Healthc Policy ; 16: 1567-1579, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37602365

RESUMO

Objective: To evaluate the psychometric properties of the 14-item health literacy scale (HL-14) in patients living with type 2 diabetes mellitus (T2DM) in clinical setting. Methods: Cross-sectional study using item response theory and structural equation modeling (SEM) for testing the item difficulty and three dimensional-HL configurations was adopted in this study. Chinese patients living with T2DM admitted to endocrinology department of Huadong hospital were evaluated by the HL-14 including communication, functional and critical health literacy from August to December 2021. Results: The multidimensional random coefficients multinomial logistic model indicated the difficulty settings of the scale are appropriate for the study populations, and differential item functioning was not observed for sex in the study. SEM demonstrated that the three-dimensional configuration of the scale is good in the study population (x2/df=2.698, Comparative Fit Index = 0.965, Root Mean Square Error of Approximation = 0.076, standard residual mean root = 0.042). Conclusion: The HL-14 scale is a reliable and valid measurement, which can perform equitably across sex in evaluating the health literacy in Chinese patients living with T2DM. Moreover, the scale may help fill the gaps of multidimensional health literacy assessment and rapid screening of health literacy ability for clinical practice.

9.
Nanomedicine (Lond) ; 18(14): 987-1002, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37584549

RESUMO

Aims: We prepared Photinia glabra (PG) aqueous fruit extract, utilized it to synthesize silver nanoparticles (PG-Ag NPs) and evaluated the antibacterial and anticancer activities of the nanoparticles (NPs). Materials & methods: Silver nitrate aqueous solution was reduced to PG-Ag NPs using aqueous PG fruit extract. NP shape, size, composition and functionalization were determined using transmission electron microscopy, x-ray photoelectron spectroscopy, Fourier transform infrared and x-ray diffraction. Results & conclusions: PG-Ag NPs were spherical, approximately 39-77 nm-sized, functionalized surfaces with notable antibacterial activity against both Escherichia coli and Staphylococcus aureus, with an MIC <30 ug/ml and cytotoxicity toward esophageal cancer cells, with IC50 values less than 20 ug/ml. PG-Ag@rt NPs have been shown to be a potent antibacterial and anticancer agent, and their enriched particle surfaces can be conjugated with other compounds for multibiomedical applications.


The present study reports for the first time the preparation of Photinia glabra (PG) aqueous fruit extract and its use for the synthesis of smaller silver particles (PG-Ag NPs) from bulk aqueous silver nitrate solution (AgNO3). The preparation followed the reduction ability of PG fruit extract phytochemical under different preparation conditions: at room temperature (PG-Ag@rt), at 70°C (PG-Ag@70) and in the presence of cerium oxide at 70°C (PG-Ag+CeO2@70). The prepared smaller particles were found using transmission electron microscopy to be spherical in shape with sizes 39, 77 and 44 nm for PG-Ag@rt, PG-Ag@70 and PG-Ag+CeO2@70, respectively. The NPs contained different functional groups on their surfaces due to the capping ability of PG fruit extract components. Among all, PG-Ag@rt NPs showed strongest antibacterial activity against Escherichia coli and Staphylococcus aureus with MIC 7.0 µg/ml and 28.0 µg/ml, respectively, and commendable anticancer activity toward Eca-109 cancer cells with IC50 less than 20 ug/ml.


Assuntos
Antibacterianos , Antineoplásicos , Nanopartículas Metálicas , Prata , Antibacterianos/farmacologia , Frutas/química , Nanopartículas Metálicas/química , Photinia/química , Extratos Vegetais/química , Prata/farmacologia , Antineoplásicos/farmacologia
10.
Patient Prefer Adherence ; 17: 217-226, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36713972

RESUMO

Purpose: Poor antidiabetic medication adherence remains a great barrier to effective diabetes self-management among aging adults. This study investigates the mediation and moderation effects of self-efficacy on the relationship between medication beliefs and adherence in elderly patients with type 2 diabetes. Methods: This cross-sectional study evaluated a sample of 309 hospitalized elderly patients who completed the assessment of medication beliefs, self-efficacy for medication uses and medication adherence in a tertiary hospital in Shanghai, China. A bootstrapping sampling method and hierarchical moderator regression analysis were used to verify the hypothesis of mediation and moderation effects of self-efficacy on the relationship between medication beliefs and adherence. Results: Self-efficacy for medication use acted as a moderator (B=-0.063, t=-2.215, p=0.028) and partial mediator (CItotal effect=4.5-16.63, p=0.001; CIindirect=1.524-5.323, p=0.014; CIdirect=2.151-11.817, p=0.001) on the relationship between general harm medication beliefs and medication adherence. Participants with lower general harm medication beliefs may develop higher self-efficacy, which, in turn, results in a higher level of medication adherence, and higher self-efficacy may attenuate the negative effect of high general harm medication beliefs on medication adherence. Conclusion: Self-efficacy for medication use not only mediated the relationship between general harm beliefs about medication and medication adherence, but moderated it negatively. The findings of this study indicate an opportunity to improve the prognosis of elderly Chinese patients with type 2 diabetes through improved medication adherence by strengthening factors such as self-efficacy for appropriate medication use and general harm beliefs about medication.

11.
Photochem Photobiol Sci ; 22(2): 427-439, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36344865

RESUMO

The synthesis of ideal photosensitizers (PSs) is considered to be the most significant bottleneck in photodynamic therapy (PDT). To discover novel PSs with excellent photodynamic anti-tumor activities, a series of novel photosensitizers 5,15-diaryl-10,20-dibromoporphyrins (I1-6) were synthesized by a facile method. Compared with hematoporphyrin monomethyl ether (HMME) as the representative porphyrin-based photosensitizers, it is found that not only the longest absorption wavelength of all compounds was red-shifted to therapeutic window (660 nm) of photodynamic therapy, but also the singlet oxygen quantum yields were significantly increased. Furthermore, all compounds exhibited lower dark toxicity (except I2) and stronger phototoxicity (except I4) against Eca-109 tumor cells than HMME. Among them, I3 possessed the highest singlet oxygen quantum yield (ΦΔ = 0.205), the lower dark toxicity and the strongest phototoxicity (IC50 = 3.5 µM) in vitro. The findings indicated the compounds I3 had the potential to become anti-tumor agents for PDT.


Assuntos
Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Porfirinas/química , Neoplasias/tratamento farmacológico
12.
Yi Chuan ; 44(8): 708-719, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384669

RESUMO

The fast-rising CRISPR-derived gene editing technologies has been widely used in the fields of life science and biomedicine, as well as plant and animal breeding. However, the efficiency of homology-directed repair (HDR), an important strategy for gene knock-in and base editing, remains to be improved. In this study, we came up with the term Donor Adapting System (DAS) to summarize those CRISPR/Cas9 systems modified with adaptor for driving aptamer-fused donor DNA. A set of CRISPR/Cas9-Gal4BD DAS was designed in our study. In this system, Gal4 DNA binding domain (Gal4BD) is used as adaptor to fuse with Cas9 protein, and Gal4 binding sequence (Gal4BS) is used as aptamer to bind to the double-stranded DNA (dsDNA) donor, in order to improve the HDR efficiency. Preliminary results from the HEK293T-HDR.GFP reporter cell line show that the HDR editing efficiency could be improved up to 2-4 times when donor homologous arms under certain length (100-60 bp). Further optimization results showed that the choice of fusion port and fusion linker would affect the expression and activity of Cas9, while the Cas9-Gal4BD fusion with a GGS5 linker was the prior choice. In addition, the HDR efficiency was likely dependent on the aptamer-dsDNA donor design, and single Gal4BD binding sequence (BS) addition to the 5'-end of intent dsDNA template was suggested. Finally, we achieved enhanced HDR editing on the endogenous AAVS1 and EMX1 sites by using the CRISPR/Gal4BD-Cas9 DAS, which we believe can be applied to facilitate animal molecular design breeding in the future.


Assuntos
Sistemas CRISPR-Cas , Reparo de DNA por Recombinação , Animais , Humanos , DNA , Células HEK293
13.
Photodiagnosis Photodyn Ther ; 39: 102955, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35690323

RESUMO

BACKGROUND: One of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). We study the photodynamic action against A549 human lung cancer cells using PS based on polycationic derivatives of synthetic bacteriochlorin. METHODS: The efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against A549 lung cancer cells were studied in vitro using immunocytochemical and morphological methods. RESULTS: It was found that PS based on tetracationic and octacationic derivatives of synthetic bacteriochlorin induce necrosis, apoptosis, decreasing of proliferative and mitotic activity, as well as reducing the number of ALDH1-positive cancer cells with signs of stem cells in A549 human lung cancer cell culture. The IC50 values (concentration of a PS that reduces cells survival by 50%) were about 0.69 µM for tetracationic PS and 0.57 µM for octacationic PS under irradiation at 30 J/cm2 while in the "dark" control they were higher than 100 µM for both PSs. CONCLUSIONS: Photosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high phototoxicity against A549 cancer cells caused by the induction of necrosis and apoptosis of cancer cells, including cells with signs of stemness, and a sharp decrease of mitotic and proliferative activity.


Assuntos
Neoplasias Pulmonares , Fotoquimioterapia , Porfirinas , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Necrose/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia
14.
J Cancer Res Clin Oncol ; 148(9): 2335-2346, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35522290

RESUMO

PURPOSE: Esophageal cancer is the most common gastrointestinal tumor and is difficult to be eradicated with conventional treatment. Porphyrin-based photosensitizers (PSs) mediated photodynamic therapy (PDT) could kill tumor cells with less damage to normal cells. As the most widely used porphyrin-based photosensitizer in clinics, Photofrin II has excellent anti-tumor effect. However, it has some disadvantages such as weak absorption at near infrared region, the complexity of components and prolonged skin photosensitivity. Here series novel 5,15-diaryl-10,20-dihalogeno porphyrin derivatives were afforded and evaluated to develop more effective and safer photosensitizers for tumor therapy. METHODS: The photophysical properties and singlet oxygen generation rates of 5,15-diaryl-10,20-dihalogeno porphyrins (I1-6, II1-4) were tested. The cytotoxicity of I1-6 and II1-4 were measured by MTT assay. The pathway of cell death was studied by flow cytometry. In vivo photodynamic efficacy of I3 and II2-4 in Eca-109 tumor-bearing BABL/c nude mice were measured and histopathological analysis were examined. RESULTS: 5,15-Diaryl-10,20-dihalogeno porphyrins I1-6 and II1-4 were synthesized. The longest absorption wavelength of these halogenated porphyrins (λmax = 660 nm) displayed a red shift around 30 nm compared to the unhalogenated porphyrins PS1 (λmax = 630 nm). The singlet oxygen generation rates of I1-6 and II1-4 were significantly higher than PS1 and HMME. All PSs mediated PDT showed obvious cytotoxic effect against Eca-109 cells compared to HMME in vitro and in vivo. Among these PSs, II4 exhibited appropriate absorption in the phototherapeutic window, higher 1O2 generation rate (k = 0.0061 s-1), the strongest phototoxicity (IC50 = 0.4 µM), lower dark toxicity, high generation of intracellular ROS in Eca-109 cells and excellent photodynamic anti-tumor efficacy in vivo. Besides, cell necrosis was induced by compound II4 mediated PDT. CONCLUSION: All new compounds have obvious photodynamic anti-esophageal cancer effects. Among them, the photosensitizer II4 showed excellent efficacy in vitro and in vivo, which has the potential to become a photodynamic anti-tumor drug.


Assuntos
Antineoplásicos , Neoplasias Esofágicas , Fotoquimioterapia , Porfirinas , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Camundongos , Camundongos Nus , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Oxigênio Singlete/uso terapêutico
15.
Photodiagnosis Photodyn Ther ; 37: 102705, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34954389

RESUMO

The synthesis, photophysicochemical and photodynamic therapy (PDT) activities of benzothiazole substituted zinc phthalocyanine (Pc): 1 (asymmetrically substituted and composed of no charges), 2 (asymmetrically substituted and composed of three positive charges), and 3 (symmetrically substituted and composed of four positive charges), are presented. The triplet and singlet oxygen quantum yields were highest for complex 2 showing the importance of asymmetry and charge. The complexes are covalently and non-covalently linked to B doped detonation nanodiamonds (B@DNDs) to yield nanohybrids (B@DNDs-1, B@DNDs-2, B@DNDs-3). The presence of B@DNDs, asymmetry and positive charge resulted in improved PDT with the lowest cell viability being observed for B@DNDs-2 at 5%. The cell viability ranged from 5% to 7% for the nanohybrids compared to 19-26% for Pcs alone.


Assuntos
Nanodiamantes , Fotoquimioterapia , Boro , Indóis/química , Indóis/farmacologia , Nanodiamantes/química , Fotoquimioterapia/métodos , Oxigênio Singlete/química
16.
Anticancer Agents Med Chem ; 22(7): 1286-1295, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33992066

RESUMO

BACKGROUND: Photodynamic therapy has been increasingly used to cope with the alarming problem of cancer. Porphyrins and their derivatives are widely used as Potent Photosensitizers (PS) for PDT. However, the hydrophobicity of porphyrins poses a challenge for their use in clinics, while most of the carbon dots (CDs) are known for good biocompatibility, solubility, and pH sensitivity. OBJECTIVE: This study aimed to improve the properties/biocompatibility of the pyropheophorbide-α for PDT. METHODS: The PPa-CD conjugate was synthesized through covalent interaction using amide condensation. The structure of synthesized conjugate was confirmed by TEM, 1HNMR, and FTIR. The absorption and emission spectra were studied. In vitro, cytotoxicity of the conjugate was examined in human esophageal cancer cell line (Eca-109). RESULTS: The results showed that the fluorescence of the drug was increased compared to its precursor. CDbased conjugate could generate ROS as well as enhanced biocompatibility by decreasing cytotoxicity. The conjugated drug also showed pH sensitivity in different solutions. CONCLUSION: The dark toxicity, as well as hemocompatibility, was improved.


Assuntos
Neoplasias , Fotoquimioterapia , Porfirinas , Carbono/química , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia
17.
Photodiagnosis Photodyn Ther ; 37: 102562, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34610430

RESUMO

BACKGROUND: A green emission up-conversion carbon-based polymer dots (CPDs) owned excellent photophysical properties and good solubility. Most photosensitizers (PS) are hydrophobic which limits their application in biomedicine. Herein we synthesized and integrated green emitting CPDs into pyropheophorbide-α (PPa) to improve the overall properties of the PS. MATERIAL AND METHODS: The nano-agent was incorporated through amide condensation and electrostatic interaction. The structure, size and morphology of the prepared conjugates were determined by FTIR, TEM, DLS, TGA, 1HNMR, Uv-vis, and fluorescence spectrophotometry. The dark and light toxicity, as well as cellular uptake, was also monitored on the human esophageal cancer cell line (Eca-109). RESULTS: Our results illustrate that the conjugation improved the PDT efficacy by increasing the ROS generation. The nano-hybrids showed pH sensitivity as well as good hemocompatibility as the hemolysis ratio was decreased when treated with nano-conjugates. PPa-CPD1 and PPa-CPD2 had the pH response and stronger ability to absorb light and produce fluorescence in an acidic environment (pH 4.0 and pH 5.0) The synthesized nano-hybrids doesnot affect the clotting time. An increase in the absorbance wavelengths was observed. The results of MTT assay showed that dark toxicity was reduced after conjugation. CONCLUSION: This CPDs-based drug enhanced tumor-inhibition efficiency as well as low dark toxicity in vitro, showing significant application potential for PDT-based treatment.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros
18.
Sci Rep ; 11(1): 10013, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976236

RESUMO

Carbon based polymer dots have piqued attention of researchers because of excellent biocompatibility, and good solubility. Most of the p-dots are able to generate ROS which is effective for photodynamic therapy for the treatment of cancer while some photosensitizers such as porphyrins possess some drawbacks such as hydrophobicity, and dark toxicity. Therefore in this study we conjugated red emission carbon based polymer with pyropheophorbide-α through amide condensation and π-π stacking. One pot synthesis of the conjugate was successfully achieved. Their photophysiological properties were studied and structures were characterized by FT-IR, TEM and 1HNMR. pH- sensitivity of the conjugates was confirmed using fluorescence and UV-vis spectroscopy. Photo toxicity and dark toxicity of the prepared conjugates were evaluated in human esophageal cancer cell line (Eca-109). Hemocompatibility of the synthesized conjugates was evaluated and proved that the conjugates are safe to use for the treatment of tumor. Our results showed the PS doped p-dots had less dark toxicity and increased light toxicity as well as ROS generation was high as compared to precursor drug. Therefore, incorporation of p-dots to porphyrin improved biocompatibility and enhanced the photodynamic effect.

19.
Photodermatol Photoimmunol Photomed ; 37(4): 296-305, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33404073

RESUMO

BACKGROUND: Antibiotic resistance is increasing day by day, thereby increase the chances of more infections by resistant bacteria. In this situation, antimicrobial photodynamic therapy (aPDT) is gaining more attraction. OBJECTIVE: To evaluate the antimicrobial effect of ALA derivatives using photodynamic therapy. MATERIALS AND METHODS: In this study, we evaluated the aPDT effect of different derivatives of 5-ALA. In vivo and in vitro studies were performed to measure the antimicrobial activity. Different light doses and different concentrations of drugs were used to test anti-bacterial effect of drugs as well as to detect any physiological changes in animal model after the treatment. RESULTS: In vivo studies revealed that ALA-methyl ester, ALA-hexyl ester, and ALA-13A are potent photosensitizers. In vitro studies involved wound healing rate, body weight, and dietary intake were evaluated, and results showed that ALA, ALA-methyl ester, ALA-hexyl ester, and ALA-13A had good anti-bacterial effects, fast healing rate, and no effect on other physical parameters. CONCLUSION: Photodynamic therapy is increasingly used to treat different types of skin infections caused by bacterial strains. Our studies revealed that ALA-methyl ester, ALA-hexyl ester, and ALA-13A are promising photosensitizers for photodynamic therapy to inhibit the growth of resistant bacterial strains.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Ácido Aminolevulínico/farmacologia , Animais , Anti-Infecciosos/farmacologia , Ésteres , Preparações Farmacêuticas , Fármacos Fotossensibilizantes/farmacologia
20.
Bioorg Chem ; 107: 104528, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33357982

RESUMO

A photosensitizer with high phototoxicity, suitable amphipathy and low dark toxicity could play a pivotal role in photodynamic therapy (PDT). In this study, a facile and versatile approach was adopted to synthesize a series of novel fluorinated hematoporphyrin ether derivatives (I1-I5 and II1-II4), and the photodynamic activities of these compounds were studied. Compared to hematoporphyrin monomethyl ether (HMME), all PSs showed preferable photodynamic activity against A549 lung tumor cells. The longest visible absorption wavelength of these compounds was approximately 622 nm. Among them, II3 revealed the highest singlet oxygen yield (0.0957 min-1), the strongest phototoxicity (IC50 = 1.24 µM), the lowest dark toxicity in vitro, and exhibited excellent anti-tumor effects in vivo. So compound II3 could act as new drug candidate for photodynamic therapy.


Assuntos
Antineoplásicos/uso terapêutico , Éteres/uso terapêutico , Hematoporfirinas/uso terapêutico , Hidrocarbonetos Fluorados/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Teoria da Densidade Funcional , Éteres/síntese química , Éteres/efeitos da radiação , Feminino , Hematoporfirinas/síntese química , Hematoporfirinas/efeitos da radiação , Humanos , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/efeitos da radiação , Luz , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Químicos , Neoplasias/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Oxigênio Singlete/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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