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1.
J Transl Med ; 22(1): 970, 2024 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-39465365

RESUMO

Gastrointestinal tumors are the main causes of death among the patients. These tumors are mainly diagnosed in the advanced stages and their response to therapy is unfavorable. In spite of the development of conventional therapeutics including surgery, chemotherapy, radiotherapy and immunotherapy, the treatment of these tumors is still challenging. As a result, the new therapeutics based on (nano)biotechnology have been introduced. Hydrogels are polymeric 3D networks capable of absorbing water to swell with favorable biocompatibility. In spite of application of hydrogels in the treatment of different human diseases, their wide application in cancer therapy has been improved because of their potential in drug and gene delivery, boosting chemotherapy and immunotherapy as well as development of vaccines. The current review focuses on the role of hydrogels in the treatment of gastrointestinal tumors. Hydrogels provide delivery of drugs (both natural or synthetic compounds and their co-delivery) along with gene delivery. Along with delivery, hydrogels stimulate phototherapy (photothermal and photodynamic therapy) in the suppression of these tumors. Besides, the ability of hydrogels for the induction of immune-related cells such as dendritic cells can boost cancer immunotherapy. For more specific cancer therapy, the stimuli-responsive types of hydrogels including thermo- and pH-sensitive hydrogels along with their self-healing ability have improved the site specific drug delivery. Moreover, hydrogels are promising for diagnosis, circulating tumor cell isolation and detection of biomarkers in the gastrointestinal tumors, highlighting their importance in clinic. Hence, hydrogels are diagnostic and therapeutic tools for the gastrointestimal tumors.


Assuntos
Neoplasias Gastrointestinais , Hidrogéis , Humanos , Hidrogéis/uso terapêutico , Hidrogéis/química , Neoplasias Gastrointestinais/terapia , Nanomedicina Teranóstica/métodos , Animais , Sistemas de Liberação de Medicamentos , Imunoterapia/métodos
2.
J Nanobiotechnology ; 22(1): 365, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918839

RESUMO

Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems.


Assuntos
Bacteriófagos , Sistemas de Liberação de Medicamentos , Nanomedicina , Bacteriófagos/genética , Humanos , Nanomedicina/métodos , Sistemas de Liberação de Medicamentos/métodos , Animais , Técnicas de Transferência de Genes , Portadores de Fármacos/química , Nanopartículas/química , Nanotecnologia/métodos
3.
Int J Mol Sci ; 25(19)2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39408866

RESUMO

Cancer therapy is constantly evolving, with a growing emphasis on targeted and efficient treatment options. In this context, graphene quantum dots (GQDs) have emerged as promising agents for precise drug and gene delivery due to their unique attributes, such as high surface area, photoluminescence, up-conversion photoluminescence, and biocompatibility. GQDs can damage cancer cells and exhibit intrinsic photothermal conversion and singlet oxygen generation efficiency under specific light irradiation, enhancing their effectiveness. They serve as direct therapeutic agents and versatile drug delivery platforms capable of being easily functionalized with various targeting molecules and therapeutic agents. However, challenges such as achieving uniform size and morphology, precise bandgap engineering, and scalability, along with minimizing cytotoxicity and the environmental impact of their production, must be addressed. Additionally, there is a need for a more comprehensive understanding of cellular mechanisms and drug release processes, as well as improved purification methods. Integrating GQDs into existing drug delivery systems enhances the efficacy of traditional treatments, offering more efficient and less invasive options for cancer patients. This review highlights the transformative potential of GQDs in cancer therapy while acknowledging the challenges that researchers must overcome for broader application.


Assuntos
Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Grafite , Neoplasias , Pontos Quânticos , Pontos Quânticos/química , Grafite/química , Humanos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/genética , Sistemas de Liberação de Medicamentos/métodos , Carbono/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/química
4.
Angew Chem Int Ed Engl ; 63(14): e202316323, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38317057

RESUMO

We synthesize supramolecular poly(disulfide) (CPS) containing covalently attached cucurbit[7]uril (CB[7]), which is exploited not only as a carrier to deliver plasmid DNA encoding destabilized Cas9 (dsCas9), but also as a host to include trimethoprim (TMP) by CB[7] moieties through the supramolecular complexation to form TMP@CPS/dsCas9. Once the plasmid is transfected into tumor cells by CPS, the presence of polyamines can competitively trigger the decomplexation of TMP@CPS, thereby displacing and releasing TMP from CB[7] to stabilize dsCas9 that can target and edit the genomic locus of PLK1 to inhibit the growth of tumor cells. Following the systemic administration of TMP@CPS/dsCas9 decorated with hyaluronic acid (HA), tumor-specific editing of PLK1 is detected due to the elevated polyamines in tumor microenvironment, greatly minimizing off-target editing in healthy tissues and non-targeted organs. As the metabolism of polyamines is dysregulated in a wide range of disorders, this study offers a supramolecular approach to precisely control CRISPR/Cas9 functions under particular pathological contexts.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Sistemas CRISPR-Cas/genética , Plasmídeos , DNA , Poliaminas
5.
Semin Cancer Biol ; 86(Pt 2): 396-419, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35700939

RESUMO

Chemotherapy is the first choice in the treatment of cancer and is always preferred to other approaches such as radiation and surgery, but it has never met the need of patients for a safe and effective drug. Therefore, new advances in cancer treatment are now needed to reduce the side effects and burdens associated with chemotherapy for cancer patients. Targeted treatment using nanotechnology are now being actively explored as they could effectively deliver therapeutic agents to tumor cells without affecting normal cells. Dendrimers are promising nanocarriers with distinct physiochemical properties that have received considerable attention in cancer therapy studies, which is partly due to the numerous functional groups on their surface. In this review, we discuss the progress of different types of dendrimers as delivery systems in cancer therapy, focusing on the challenges, opportunities, and functionalities of the polymeric molecules. The paper also reviews the various role of dendrimers in their entry into cells via endocytosis, as well as the molecular and inflammatory pathways in cancer. In addition, various dendrimers-based drug delivery (e.g., pH-responsive, enzyme-responsive, redox-responsive, thermo-responsive, etc.) and lipid-, amino acid-, polymer- and nanoparticle-based modifications for gene delivery, as well as co-delivery of drugs and genes in cancer therapy with dendrimers, are presented. Finally, biosafety concerns and issues hindering the transition of dendrimers from research to the clinic are discussed to shed light on their clinical applications.


Assuntos
Dendrímeros , Nanopartículas , Neoplasias , Humanos , Dendrímeros/química , Dendrímeros/uso terapêutico , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Nanotecnologia , Neoplasias/tratamento farmacológico
6.
Environ Res ; 237(Pt 2): 117027, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37659647

RESUMO

The latest advancements in oncology involves the creation of multifunctional nanostructures. The integration of nanoparticles into the realm of cancer therapy has brought about a transformative shift, revolutionizing the approach to addressing existing challenges and limitations in tumor elimination. This is particularly crucial in combating the emergence of resistance, which has significantly undermined the effectiveness of treatments like chemotherapy and radiotherapy. GO stands as a carbon-derived nanoparticle that is increasingly finding utility across diverse domains, notably in the realm of biomedicine. The utilization of GO nanostructures holds promise in the arena of oncology, enabling precise transportation of drugs and genetic material to targeted sites. GO nanomaterials offer the opportunity to enhance the pharmacokinetic behavior and bioavailability of drugs, with documented instances of these nanocarriers elevating drug accumulation at the tumor location. The GO nanostructures encapsulate genes, shielding them from degradation and facilitating their uptake within cancer cells, thereby promoting efficient gene silencing. The capability of GO to facilitate phototherapy has led to notable advancements in reducing tumor progression. By PDT and PTT combination, GO nanomaterials hold the capacity to diminish tumorigenesis. GO nanomaterials have the potential to trigger both cellular and innate immunity, making them promising contenders for vaccine development. Additionally, types of GO nanoparticles that respond to specific stimuli have been applied in cancer eradication, as well as for the purpose of cancer detection and biomarker diagnosis. Endocytosis serves as the mechanism through which GO nanomaterials are internalized. Given these advantages, the utilization of GO nanomaterials for tumor elimination comes highly recommended.

7.
Environ Res ; 234: 116507, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37364628

RESUMO

The interest towards application of nanomaterials in field of cancer therapy is that the drawbacks of conventional therapies including chemoresistance, radio-resistance and lack of specific targeting of tumor cells can be solved by nanotechnology. Cyclodextrins (CDs) are amphiphilic cyclic oligosaccharides that can be present in three forms of α-, ß- and γ-CDs, and they can be synthesized from natural sources. The application of CDs in cancer shows an increasing trend due to benefits of these nanocomplexes in improving solubility and bioavailability of current bioactives and therapeutics for cancer. CDs are widely utilized in delivery of drugs and genes in cancer therapy, and by targeted delivery of these therapeutics into target site, they improve anti-proliferative and anti-cancer potential. The blood circulation time and tumor site accumulation of therapeutics can be improved using CD-based nanostructures. More importantly, the stimuli-responsive types of CDs including pH-, redox- and light-sensitive types can accelerate release of bioactive compound at tumor site. Interestingly, the CDs are able to mediate photothermal and photodynamic impact in impairing tumorigenesis in cancer, enhancing cell death and improving response to chemotherapy. In improving the targeting ability of CDs, their surface functionalization with ligands has been conducted. Moreover, CDs can be modified with green products such as chitosan and fucoidan, and they can be embedded in green-based nanostructures to suppress tumorigenesis. The internalization of CDs into tumor cells can occur through endocytosis and this can be clethrin-, caveolae- or receptor-mediated endocytosis. Furthermore, CDs are promising candidates in bioimaging, cancer cell and organelle imaging as well as isolating tumor cells. The main benefits of using CDs in cancer therapy including sustained and low release of drugs and genes, targeted delivery, bioresponsive release of cargo, ease of surface functionalization and complexation with other nanostructures. The application of CDs in overcoming drug resistance requires more investigation.


Assuntos
Ciclodextrinas , Neoplasias , Humanos , Ciclodextrinas/química , Sistemas de Liberação de Medicamentos/métodos , Preparações Farmacêuticas , Imunoterapia , Neoplasias/tratamento farmacológico , Carcinogênese
8.
Environ Res ; 229: 115939, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37088317

RESUMO

Constructive achievements in the field of nanobiotechnology and their translation into clinical course have led to increasing attention towards evaluation of their use for treatment of diseases, especially cancer. Osteosarcoma (OS) is one of the primary bone malignancies that affects both males and females in childhood and adolescence. Like other types of cancers, genetic and epigenetic mutations account for OS progression and several conventional therapies including chemotherapy and surgery are employed. However, survival rate of OS patients remains low and new therapies in this field are limited. The purpose of the current review is to provide a summary of nanostructures used in OS treatment. Drug and gene delivery by nanoplatforms have resulted in an accumulation of therapeutic agents for tumor cell suppression. Furthermore, co-delivery of genes and drugs by nanostructures are utilized in OS suppression to boost immunotherapy. Since tumor cells have distinct features such as acidic pH, stimuli-responsive nanoparticles have been developed to appropriately target OS. Besides, nanoplatforms can be used for biosensing and providing phototherapy to suppress OS. Furthermore, surface modification of nanoparticles with ligands can increase their specificity and selectivity towards OS cells. Clinical translation of current findings suggests that nanoplatforms have been effective in retarding tumor growth and improving survival of OS patients.


Assuntos
Neoplasias Ósseas , Nanopartículas , Osteossarcoma , Adolescente , Feminino , Humanos , Sistemas de Liberação de Medicamentos , Medicina de Precisão , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Nanopartículas/química
9.
Environ Res ; 237(Pt 1): 116951, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37633628

RESUMO

Nanomedicine application in cancer therapy is an urgency because of inability of current biological therapies for complete removal of tumor cells. The development of smart and novel nanoplatforms for treatment of cancer can provide new insight in tumor suppression. Hyaluronic acid is a biopolymer that can be employed for synthesis of smart nanostructures capable of selective targeting CD44-overexpressing tumor cells. The breast and lung cancers are among the most malignant and common tumors in both females and males that environmental factors, lifestyle and genomic alterations are among the risk factors for their pathogenesis and development. Since etiology of breast and lung tumors is not certain and multiple factors participate in their development, preventative measures have not been completely successful and studies have focused on developing new treatment strategies for them. The aim of current review is to provide a comprehensive discussion about application of hyaluronic acid-based nanostructures for treatment of breast and lung cancers. The main reason of using hyaluronic acid-based nanoparticles is their ability in targeting breast and lung cancers in a selective way due to upregulation of CD44 receptor on their surface. Moreover, nanocarriers developed from hyaluronic acid or functionalized with hyaluronic acid have high biocompatibility and their safety is appreciated. The drugs and genes used for treatment of breast and lung cancers lack specific accumulation at cancer site and their cytotoxicity is low, but hyaluronic acid-based nanostructures provide their targeted delivery to tumor site and by increasing internalization of drugs and genes in breast and lung tumor cells, they improve their therapeutic index. Furthermore, hyaluronic acid-based nanostructures can be used for phototherapy-mediated breast and lung cancers ablation. The stimuli-responsive and smart kinds of hyaluronic acid-based nanostructures such as pH- and light-responsive can increase selective targeting of breast and lung cancers.

10.
Mol Pharm ; 18(3): 1208-1228, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33371687

RESUMO

Hydrocortisone, a natural glucocorticoid secreted by adrenal and extra-adrenal tissues, locally governs the transcription of genes involved in inflammation, immune response, metabolism, and energy homeostasis via binding to its cognate glucocorticoid receptor (GR). In this study, we show that modified hydrocortisone (HC16), a cancer-selective cytotoxic molecule, showed synergism in combination with drugs like Doxorubicin and docetaxel, self-assembled into vesicles, entrapped docetaxel and complexed with anti-cancer plasmid DNA for enhanced killing of cancer cells. These vesicles exhibited GR-mediated nuclear localization, delivery of the p53 gene, and also inhibited cell viability selectively in RKO, HCT15, and CT26 colon cancer cells but not in normal cells like CHO and HEK293T. Apart from exerting its own anti-cancer activity, the self-assembled HC16 vesicles loaded with docetaxel sensitized the cancer cells to its drug cargo by downregulating the drug metabolizing CYP3A4 gene. This indirectly reduces the risk of nonspecific adverse effects in normal cells, as the viability of sensitized cancer cells could be significantly reduced even in low doses of cytotoxic docetaxel. The near infrared (NIR)-dye-associated self-assemblies accumulated in a colon tumor with higher orders of NIR intensity compared to those in a colon of healthy mice. Thereafter, the treatment of HC16-docetaxel-p53 vesicle/DNA complex led to significant tumor regression, which resulted in a cecum/body weight ratio in tumor-bearing mice similar to that of healthy mice measured at 24 h postcompletion of treatment. There was an up to 2.5-fold enhancement in the overall survivability of colon-tumor-bearing mice treated with HC16-docetaxel-p53 vesicle/DNA complexes when compared against the pristine docetaxel-treated groups. Further, the HC16-docetaxel-p53 vesicle/DNA complex-treated group showed reduced nuclear accumulation of cell proliferation marker Ki67, reduced protein levels of prosurvival and mesenchymal proteins like Bcl-2, PARP, vimentin, and N-cadherin, and increased the levels of pro-apoptotic activated caspases as compared to the pristine docetaxel-treated groups. The therapeutic package described herein is expected to find future use as a rational, multifaceted, GR-targeted approach for inhibiting colon tumor progression.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Hidrocortisona/farmacologia , Receptores de Glucocorticoides/metabolismo , Células A549 , Animais , Apoptose/efeitos dos fármacos , Células CHO , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Cricetulus , Docetaxel/farmacologia , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3
11.
Int J Mol Sci ; 20(12)2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31238531

RESUMO

Many pathological conditions are characterized or caused by the presence of an insufficient or aberrant local vasculature. Thus, therapeutic approaches aimed at modulating the caliber and/or density of the vasculature by controlling angiogenesis and arteriogenesis have been under development for many years. As our understanding of the underlying cellular and molecular mechanisms of these vascular growth processes continues to grow, so too do the available targets for therapeutic intervention. Nonetheless, the tools needed to implement such therapies have often had inherent weaknesses (i.e., invasiveness, expense, poor targeting, and control) that preclude successful outcomes. Approximately 20 years ago, the potential for using ultrasound as a new tool for therapeutically manipulating angiogenesis and arteriogenesis began to emerge. Indeed, the ability of ultrasound, especially when used in combination with contrast agent microbubbles, to mechanically manipulate the microvasculature has opened several doors for exploration. In turn, multiple studies on the influence of ultrasound-mediated bioeffects on vascular growth and the use of ultrasound for the targeted stimulation of blood vessel growth via drug and gene delivery have been performed and published over the years. In this review article, we first discuss the basic principles of therapeutic ultrasound for stimulating angiogenesis and arteriogenesis. We then follow this with a comprehensive cataloging of studies that have used ultrasound for stimulating revascularization to date. Finally, we offer a brief perspective on the future of such approaches, in the context of both further research development and possible clinical translation.


Assuntos
Neovascularização Fisiológica/efeitos da radiação , Ondas Ultrassônicas , Remodelação Vascular/efeitos da radiação , Indutores da Angiogênese/administração & dosagem , Indutores da Angiogênese/metabolismo , Animais , Materiais Biocompatíveis , Biomarcadores , Meios de Contraste , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Humanos , Microbolhas , Neovascularização Patológica/terapia , Terapia por Ultrassom/métodos
12.
Int J Mol Sci ; 20(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035393

RESUMO

For decades, macrocyclic compounds have been widely applied in various fields owing to essential physicochemical properties such as their rigid cyclic structures, geometric dimensions (diameter and height), hydrophobic cavity, and hydrophilic interface. This review is an attempt to summarize various research accomplishments involving macrocyclic compounds for drug and gene delivery in immune-modulating therapies: the structures and benefits of main host molecules, their mechanisms regulating the immune system from cell uptake to activation of dendritic cells and T helper lymphocytes, as well as their potential immunotherapy for different diseases. Macrocyclic compounds including cucurbiturils (CBs), calixarenes, pillararenes, cyclodextrins (CyDs), macrocyclic peptides and metallo-supramolecular compounds, have their own unique physicochemical properties and functional derivatizations that enable to improve the biocompatibility, responsiveness to stimuli, and effectiveness of immune-modulating therapy. Based on abundant clarifications of the biological immunity mechanisms, representative constructions of macrocyclic compounds for immune therapies have been conducted for the investigation of treatment of different diseases including cancer, atherosclerosis, Niemann-Pick type C1 disease (NPC1), diabetes, and inflammations. Although there are critical challenges that remain to be conquered, we believe the future of macrocyclic compounds in the immune-modulating therapy must be bright.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Compostos Macrocíclicos/administração & dosagem , Animais , Técnicas de Transferência de Genes , Humanos , Imunoterapia/métodos
13.
Nanomedicine ; 13(1): 153-171, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27591961

RESUMO

Mucus is a viscoelastic and adhesive obstacle which protects vaginas, eyes and other mucosal surfaces against foreign pathogens. Numerous diseases that affect the mucosa could be afforded prophylactic and therapeutic treatments with fewer systemic side effects if drugs and genes could be sufficiently delivered to the target mucosal tissues. But drugs and genes are trapped effectively like other pathogens and rapidly removed by mucus clearance mechanism. The emergence of micro- and nano-delivery technologies combined with the realization of non-invasive and painless administration routes brings new hope for the treatment of disease. For retained drugs and genes to mucosal tissues, carriers must increase retention time in the mucus to make full contact with epithelial cells and be transported to target tissues. This review focuses on the current development of micro- and nano-carriers to improve the localized therapeutic efficiency of targeted and sustained drug and gene delivery in mucosal tissues.


Assuntos
Sistemas de Liberação de Medicamentos , Mucosa/metabolismo , Muco/química , Nanoestruturas/química , Animais , Técnicas de Transferência de Genes , Humanos , Preparações Farmacêuticas
14.
Nanomedicine ; 11(2): 401-5, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25461289

RESUMO

Mucus barriers lining mucosal epithelia reduce the effectiveness of nanocarrier-based mucosal drug delivery and imaging ("theranostics"). Here, we describe liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, e.g., the diaCEST MRI contrast agent barbituric acid (BA). We observed that polyethylene glycol (PEG)-coated liposomes containing ≥7 mol% PEG diffused only ~10-fold slower in human cervicovaginal mucus (CVM) compared to their theoretical speeds in water. 7 mol%-PEG liposomes contained sufficient BA loading for diaCEST contrast, and provided improved vaginal distribution compared to 0 and 3mol%-PEG liposomes. However, increasing PEG content to ~12 mol% compromised BA loading and vaginal distribution, suggesting that PEG content must be optimized to maintain drug loading and stability. Non-invasive diaCEST MRI illustrated uniform vaginal coverage and longer retention of BA-loaded 7 mol%-PEG liposomes compared to unencapsulated BA. Liposomal MPP with optimized PEG content hold promise for drug delivery and imaging at mucosal surfaces. FROM THE CLINICAL EDITOR: This team of authors characterized liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, such as barbituric acid (a diaCEST MRI contrast agent) and concluded that liposomal MPP with optimized PEG coating enables drug delivery and imaging at mucosal surfaces.


Assuntos
Muco do Colo Uterino/diagnóstico por imagem , Sistemas de Liberação de Medicamentos , Imageamento por Ressonância Magnética , Mucosa/diagnóstico por imagem , Barbitúricos/química , Muco do Colo Uterino/efeitos dos fármacos , Meios de Contraste , Humanos , Lipossomos , Mucosa/patologia , Nanopartículas/química , Polietilenoglicóis/química , Radiografia
15.
Nanomedicine ; 11(7): 1773-84, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25959925

RESUMO

Herein, chiral selenium nanoparticles (L-SeNPs/D-SeNPs) modified with a dinuclear Ruthenium (II) complex were used to effectively deliver siRNA targeting the MDR1 gene. In this co-delivery system, the luminescent dinuclear Ruthenium (II) complex was developed to act as a gene carrier and anti-tumor drug, while offering luminescent imaging to follow the intracellular trafficking. Interestingly, Ru@L-SeNPs exhibited a stronger protein and pDNA affinity than Ru@D-SeNPs, indicating that chirality may have an effect on pDNA/siRNA binding and biocompatibility. Cisplatin-resistant A549R cells treated with Ru@L-SeNPs-siRNA demonstrated significant downregulation of P-glycoprotein (P-gp) expression, resulting in unprecedented enhanced cytotoxicity through the induction of apoptosis with the involvement of phosphorylation of p53, MAPK and PI3K/Akt signaling pathways. In vivo investigation confirmed that Ru@L-SeNPs-siRNA nanoparticles exhibited high tumor-targeted fluorescence, enhanced anti-tumor efficacy, and decreased systemic toxicity. These results suggest that Ru@L-SeNPs are promising vectors for the delivery of siRNA and for real-time tracking of treatment. FROM THE CLINICAL EDITOR: In this study, the authors designed bi-functional selenium nanoparticles with specific chirality to deliver siRNA, for targeting tumor MDR1 gene. The underlying ruthenium (II) complex could also offer fluorescence for real-time imaging. This new system has been shown to have enhanced efficacy against drug resistant tumor cells in both in-vitro and in-vivo experiments.


Assuntos
Técnicas de Transferência de Genes , Nanopartículas/administração & dosagem , Neoplasias/terapia , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Apoptose/genética , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Nanopartículas/química , Neoplasias/genética , Neoplasias/patologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Rutênio/química , Selênio/administração & dosagem , Selênio/química
16.
Drug Discov Today ; 29(1): 103851, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38092146

RESUMO

Breast cancer is the most common and malignant tumor among women. Chitosan (CS)-based nanoparticles have been introduced into breast cancer therapy as a way to increase the targeted delivery of drugs and genes to the tumor site. CS nanostructures suppress tumorigenesis by enhancing both the targeted delivery of cargo (drug and gene) and its accumulation in tumor cells. The tumor cells internalize CS-based nanoparticles through endocytosis. Moreover, chitosan nanocarriers can also induce phototherapy-mediated tumor ablation. Smart and multifunctional types of CS nanoparticles, including pH-, light- and redox-responsive nanoparticles, can be used to improve the potential for breast cancer removal. In addition, the acceleration of immunotherapy by CS nanoparticles has also been achieved, and there is potential to develop CS-nanoparticle hydrogels that can be used to suppress tumorigenesis.


Assuntos
Neoplasias da Mama , Quitosana , Nanopartículas , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Sistemas de Liberação de Medicamentos , Fototerapia , Nanopartículas/química , Carcinogênese , Imunoterapia , Concentração de Íons de Hidrogênio
17.
Int J Biol Macromol ; 260(Pt 2): 129391, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242413

RESUMO

The nanotechnology is an interdisciplinary field that has become a hot topic in cancer therapy. Metal-organic frameworks (MOFs) are porous materials and hybrid composites consisted of organic linkers and metal cations. Despite the wide application of MOFs in other fields, the potential of MOFs for purpose of cancer therapy has been revealed by the recent studies. High surface area and porosity, significant drug loading and encapsulation efficiency are among the benefits of using MOFs in drug delivery. MOFs can deliver genes/drugs with selective targeting of tumor cells that can be achieved through functionalization with ligands. The photosensitizers and photo-responsive nanostructures including carbon dots and gold nanoparticles can be loaded in/on MOFs to cause phototherapy-mediated tumor ablation. The immunogenic cell death induction and increased infiltration of cytotoxic CD8+ and CD4+ T cells can be accelerated by MOF platforms in providing immunotherapy of tumor cells. The stimuli-responsive MOF platforms responsive to pH, redox, enzyme and ion can accelerate release of therapeutics in tumor site. Moreover, MOF nanocomposites can be modified ligands and green polymers to improve their selectivity and biocompatibility for cancer therapy. The application of MOFs for the detection of cancer-related biomarkers can participate in the early diagnosis of patients.


Assuntos
Nanopartículas Metálicas , Estruturas Metalorgânicas , Nanocompostos , Neoplasias , Humanos , Estruturas Metalorgânicas/química , Ouro , Biomimética , Fototerapia , Sistemas de Liberação de Medicamentos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Nanocompostos/uso terapêutico
18.
ACS Appl Bio Mater ; 7(4): 2086-2127, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38512809

RESUMO

Carbon nanodots (CNDs), a fascinating carbon-based nanomaterial (typical size 2-10 nm) owing to their superior optical properties, high biocompatibility, and cell penetrability, have tremendous applications in different interdisciplinary fields. Here, in this Review, we first explore the superiority of CNDs over other nanomaterials in the biomedical, optoelectronics, analytical sensing, and photocatalysis domains. Beginning with synthesis, characterization, and purification techniques, we even address fundamental questions surrounding CNDs such as emission origin and excitation-dependent behavior. Then we explore recent advancements in their applications, focusing on biological/biomedical uses like specific organelle bioimaging, drug/gene delivery, biosensing, and photothermal therapy. In optoelectronics, we cover CND-based solar cells, perovskite solar cells, and their role in LEDs and WLEDs. Analytical sensing applications include the detection of metals, hazardous chemicals, and proteins. In catalysis, we examine roles in photocatalysis, CO2 reduction, water splitting, stereospecific synthesis, and pollutant degradation. With this Review, we intend to further spark interest in CNDs and CND-based composites by highlighting their many benefits across a wide range of applications.


Assuntos
Carbono , Nanoestruturas , Carbono/química , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Catálise
19.
Adv Drug Deliv Rev ; 185: 114257, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35381306

RESUMO

RNA binding proteins (RBPs) enact a very crucial part in the RNA directive processes. Atypical expression of these RBPs affects many steps of RNA metabolism, majorly altering its expression. Altered expression and dysfunction of RNA binding proteins lead to cancer progression and other diseases. We enumerate various available interventions, and recent findings focused on targeting RBPs for cancer therapy and diagnosis. The treatment, sensitization, chemoprevention, gene-mediated, and virus mediated interventions were studied to treat and diagnose cancer. The application of passively and actively targeted lipidic nanoparticles, polymeric nanoparticles, virus-based particles, and vaccine-based immunotherapy for the delivery of therapeutic agent/s against cancer are discussed. We also discuss the formulation aspect of nanoparticles for achieving delivery at the site of action and ongoing clinical trials targeting RBPs.


Assuntos
Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Polímeros/metabolismo , RNA , Proteínas de Ligação a RNA/metabolismo
20.
Biomedicines ; 9(7)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34356867

RESUMO

Acute respiratory distress syndrome (ARDS) is characterized by increased permeability of the alveolar-capillary membrane, a thin barrier composed of adjacent monolayers of alveolar epithelial and lung microvascular endothelial cells. This results in pulmonary edema and severe hypoxemia and is a common cause of death after both viral (e.g., SARS-CoV-2) and bacterial pneumonia. The involvement of the lung in ARDS is notoriously heterogeneous, with consolidated and edematous lung abutting aerated, less injured regions. This makes treatment difficult, as most therapeutic approaches preferentially affect the normal lung regions or are distributed indiscriminately to other organs. In this review, we describe the use of thoracic ultrasound and microbubbles (USMB) to deliver therapeutic cargo (drugs, genes) preferentially to severely injured areas of the lung and in particular to the lung endothelium. While USMB has been explored in other organs, it has been under-appreciated in the treatment of lung injury since ultrasound energy is scattered by air. However, this limitation can be harnessed to direct therapy specifically to severely injured lungs. We explore the cellular mechanisms governing USMB and describe various permutations of cargo administration. Lastly, we discuss both the challenges and potential opportunities presented by USMB in the lung as a tool for both therapy and research.

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