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1.
Nat Commun ; 15(1): 4366, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777821

RESUMO

Rapid uptake of nanoparticles by mononuclear phagocyte system (MPS) significantly hampers their therapeutic efficacy. Temporal MPS blockade is one of the few ways to overcome this barrier - the approach rediscovered many times under different names but never extensively used in clinic. Using meta-analysis of the published data we prove the efficacy of this technique for enhancing particle circulation in blood and their delivery to tumours, describe a century of its evolution and potential combined mechanism behind it. Finally, we discuss future directions of the research focusing on the features essential for successful clinical translation of the method.


Assuntos
Sistemas de Liberação de Medicamentos , Sistema Fagocitário Mononuclear , Nanopartículas , Humanos , Sistema Fagocitário Mononuclear/metabolismo , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Animais , Sistemas de Liberação de Fármacos por Nanopartículas/química
2.
Mikrochim Acta ; 191(6): 326, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740583

RESUMO

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.


Assuntos
Movimento Celular , Quimioterapia Combinada , Nanopartículas , Neoplasias , Dióxido de Silício , Movimento Celular/efeitos dos fármacos , Dióxido de Silício/química , Quimioterapia Combinada/métodos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Sistemas de Liberação de Fármacos por Nanopartículas/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanopartículas/ultraestrutura , Células A549 , Microscopia Eletrônica de Transmissão , Humanos
3.
Eur J Pharm Biopharm ; 199: 114310, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705311

RESUMO

Nanoparticle-based drug delivery systems hold potential in chemotherapy, but their limited accumulation in tumor tissues hinders effective drug concentration for combating tumor growth. Hence, altering the physicochemical properties of nanoparticles, particularly their surface charge, can enhance their performance. This study utilized a computational model to explore a nanoparticle drug delivery system capable of dynamically adjusting its surface charge. In the model, nanoparticles in the bloodstream were assigned a neutral or positive charge, which, upon reaching the tumor microenvironment, switched to a neutral or negative charge, and releasing chemotherapy drugs into the extracellular space. Results revealed that circulating nanoparticles with a positive surface charge, despite having a shorter circulation and high clearance rate compared to their neutral counterparts, could accumulate significantly in the tissue due to their high transvascular rate. After extravasation, neutralized surface-charged nanoparticles tended to accumulate only near blood microvessels due to their low diffusion rate, resulting in substantial released drug drainage back into the bloodstream. On the other hand, nanoparticles with a negative surface charge in the tumor's extracellular space, due to the reduction of nano-bio interactions, were able to penetrate deeper into the tumor, and increasing drug bioavailability by reducing the volume of drained drugs. Furthermore, the analysis suggested that burst drug release yields a higher drug concentration than sustained drug release, however their creation of bioavailability dependent on nanoparticle accumulation in the tissue. The study's findings demonstrate the potential of this delivery system and offer valuable insights for future research in this area.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Nanopartículas/química , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Humanos , Microambiente Tumoral/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Disponibilidade Biológica , Liberação Controlada de Fármacos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Simulação por Computador , Distribuição Tecidual , Portadores de Fármacos/química
4.
Yakugaku Zasshi ; 144(5): 511-519, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38692926

RESUMO

Nanoparticles, including liposomes and lipid nanoparticles, have garnered global attention due to their potential applications in pharmaceuticals, vaccines, and gene therapies. These particles enable targeted delivery of new drug modalities such as highly active small molecules and nucleic acids. However, for widespread use of nanoparticle-based formulations, it is crucial to comprehensively analyze their characteristics to ensure both efficacy and safety, as well as enable consistent production. In this context, this review focuses on our research using atomic force microscopy (AFM) to study liposomes and lipid nanoparticles. Our work significantly contributes to the capability of AFM to measure various types of liposomes in an aqueous medium, providing valuable insights into the mechanical properties of these nanoparticles. We discuss the applications of this AFM technique in assessing the quality of nanoparticle-based pharmaceuticals and developing membrane-active peptides.


Assuntos
Lipossomos , Microscopia de Força Atômica , Nanopartículas , Microscopia de Força Atômica/métodos , Lipídeos/química , Sistemas de Liberação de Medicamentos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Peptídeos/química
5.
J Cancer Res Ther ; 20(2): 684-694, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687941

RESUMO

OBJECTIVES: Gypenoside (Gyp) is easily degraded in the gastrointestinal tract, resulting in its low bioavailability. We aimed to develop a tumor-targeted Gyp nanodrug delivery system and to investigate its antitumor effect in vitro. MATERIALS AND METHODS: We used Gyp as the therapeutic drug molecule, mesoporous silica (MSN) and liposome (Lipo) as the drug carrier and protective layers, and aptamer SYL3C as the targeting element to establish a tumor-targeted nanodrug delivery system (i.e., SYL3C-Lipo@Gyp-MSN). The characteristics of SYL3C-Lipo@Gyp-MSN were investigated, and its drug release performance, cell uptake, and antitumor activity in vitro were evaluated. RESULTS: A tumor-targeted Gyp nanodrug delivery system was successfully prepared. The SYL3C-Lipo@Gyp-MSN was spherical or ellipsoidal; had good dispersion, which enabled it to specifically target and kill the liver tumor cell HepG2; and effectively protected the early leakage of Gyp. CONCLUSIONS: We have established a tumor-targeted nanodrug delivery system that can target and kill liver cancer cells and may provide a strategy for preparing new nanodrug-loaded preparations of traditional Chinese medicine.


Assuntos
Gynostemma , Lipossomos , Humanos , Gynostemma/química , Lipossomos/química , Células Hep G2 , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/química , Dióxido de Silício/química , Liberação Controlada de Fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Nanopartículas/química , Nanopartículas/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Sistemas de Liberação de Fármacos por Nanopartículas/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem
6.
Drug Des Devel Ther ; 18: 1007-1022, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567254

RESUMO

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.


Assuntos
Degeneração do Disco Intervertebral , Dor Lombar , Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Manejo da Dor , Liberação Controlada de Fármacos , Sistemas de Liberação de Fármacos por Nanopartículas
7.
Sci Rep ; 14(1): 8567, 2024 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609391

RESUMO

A novel pH/redox-responsive hyperbranched MeO-PEG-b-(NIPAAm-co-PBAE) nanoparticles (NPs) were designed with size shrinkage and charge-reversible potential for targeted delivery of docetaxel (DTX) to MDA-MB-231 cell lines. In the tumor microenvironment (TME), amine protonation induces charge reversal and disulfide bond cleavage under high TME GSH concentration causing size shrinkage, improved deep tumor penetration, and active targeting of the therapeutic agents. These nano drug delivery systems (NDDSs) significantly promoted cancer cell uptake (~ 100% at 0.5 h), facilitating site-specific delivery and deep tumor penetration. The MTT assay revealed significantly higher cytotoxicity (P value < 0.0001) for DTX-loaded NPs compared to free DTX. Cell cycle analysis revealed G2/M (58.3 ± 2.1%) and S (21.5 ± 1.3%) arrest for DTX-loaded NPs, while free DTX caused G2/M (67.9 ± 1.1%) and sub-G1 (10.3 ± 0.8%) arrest. DTX-loaded NPs induced higher apoptosis (P value < 0.001) in MDA-MB-231 cells (71.5 ± 2.8%) compared to free DTX (42.3 ± 3.1%). Western blotting and RT-PCR assays confirmed significant up-regulation of protein levels and apoptotic genes by DTX-loaded NPs compared to free DTX. In conclusion, TME-responsive charge reversal and size-shrinkable smart NDDSs designed based on low pH, and high glutathione (GSH), offer more effective site-specific delivery of therapeutic agents to tumors.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Docetaxel/farmacologia , Glutationa , Sistemas de Liberação de Fármacos por Nanopartículas , Oxirredução , Polímeros , Concentração de Íons de Hidrogênio
8.
Mol Pharm ; 21(5): 2148-2162, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38536949

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer for which effective therapies are lacking. Targeted remodeling of the immunosuppressive tumor microenvironment (TME) and activation of the body's immune system to fight tumors with well-designed nanoparticles have emerged as pivotal breakthroughs in tumor treatment. To simultaneously remodel the immunosuppressive TME and trigger immune responses, we designed two potential therapeutic nanodelivery systems to inhibit TNBC. First, the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 and the cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) were coloaded into chondroitin sulfate (CS) to obtain CS@JQ1/CXB nanoparticles (NPs). Then, the biomimetic nanosystem MM@P3 was prepared by coating branched polymer poly(ß-amino ester) self-assembled NPs with melittin embedded macrophage membranes (MM). Both in vitro and in vivo, the CS@JQ1/CXB and MM@P3 NPs showed excellent immune activation efficiencies. Combination treatment exhibited synergistic cytotoxicity, antimigration ability, and apoptosis-inducing and immune activation effects on TNBC cells and effectively suppressed tumor growth and metastasis in TNBC tumor-bearing mice by activating the tumor immune response and inhibiting angiogenesis. In summary, this study offers a novel combinatorial immunotherapeutic strategy for the clinical TNBC treatment.


Assuntos
Azepinas , Celecoxib , Triazóis , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Feminino , Camundongos , Humanos , Celecoxib/administração & dosagem , Linhagem Celular Tumoral , Sulfatos de Condroitina/química , Sulfatos de Condroitina/administração & dosagem , Nanopartículas/química , Nanopartículas/administração & dosagem , Meliteno/administração & dosagem , Meliteno/química , Apoptose/efeitos dos fármacos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Polímeros/química , Camundongos Nus , Sistemas de Liberação de Medicamentos/métodos
9.
Int J Nanomedicine ; 19: 2823-2849, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525013

RESUMO

Currently, pancreatic cancer (PC) is one of the most lethal malignant tumors. PC is typically diagnosed at a late stage, exhibits a poor response to conventional treatment, and has a bleak prognosis. Unfortunately, PC's survival rate has not significantly improved since the 1960s. Cancer-associated fibroblasts (CAFs) are a key component of the pancreatic tumor microenvironment (TME). They play a vital role in maintaining the extracellular matrix and facilitating the intricate communication between cancer cells and infiltrated immune cells. Exploring therapeutic approaches targeting CAFs may reverse the current landscape of PC therapy. In recent years, nano-drug delivery systems have evolved rapidly and have been able to accurately target and precisely release drugs with little or no toxicity to the whole body. In this review, we will comprehensively discuss the origin, heterogeneity, potential targets, and recent advances in the nano-drug delivery system of CAFs in PC. We will also propose a novel integrated treatment regimen that utilizes a nano-drug delivery system to target CAFs in PC, combined with radiotherapy and immunotherapy. Additionally, we will address the challenges that this regimen currently faces.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Pancreáticas , Humanos , Sistemas de Liberação de Fármacos por Nanopartículas , Neoplasias Pancreáticas/tratamento farmacológico , Imunoterapia , Pâncreas , Microambiente Tumoral
10.
Cancer Med ; 13(5): e7010, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38491817

RESUMO

Cancer remains a leading cause of death worldwide, necessitating the development of innovative and more effective treatment strategies. Conventional cancer treatments often suffer from limitations such as systemic toxicity, poor pharmacokinetics, and drug resistance. Recently, there has been growing attention to utilizing natural compounds derived from various sources as possible cancer therapeutics. Natural compounds have demonstrated diverse bioactive properties, including antioxidant, anti-inflammatory, and antitumor effects, making them attractive candidates for cancer treatment. However, their limited solubility and bioavailability present challenges for effective delivery to cancer cells. To overcome these limitations, researchers have turned to nanotechnology-based drug delivery systems. Nanoparticles, with their small size and unique properties, can encapsulate therapeutic agents and offer benefits such as improved solubility, prolonged drug release, enhanced cellular uptake, and targeted delivery. Functionalizing nanoparticles with specific ligands further enhances their precision in recognizing and binding to cancer cells. Combining natural compounds with nanotechnology holds great promise in achieving efficient and safe cancer treatments by enhancing bioavailability, pharmacokinetics, and selectivity toward cancer cells. This review article provides an overview of the advancements in utilizing natural substances and nanotechnology-based drug delivery systems for cancer treatment. It discusses the benefits and drawbacks of various types of nanoparticles, as well as the characteristics of natural compounds that make them appealing for cancer therapy. Additionally, current research on natural substances and nanoparticles in preclinical and clinical settings is highlighted. Finally, the challenges and future perspectives in developing natural compound-nanoparticle-based cancer therapies are discussed.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Fármacos por Nanopartículas , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Nanopartículas/química
11.
Artigo em Inglês | MEDLINE | ID: mdl-38528388

RESUMO

The conventional therapeutic treatment of triple-negative breast cancer (TNBC) is negatively influenced by the development of tumor cell drug resistant, and systemic toxicity of therapeutic agents due to off-target activity. In accordance with research findings, nanoparticles (NPs) responsive to the tumor microenvironment (TME) have been discovered for providing opportunities to selectively target tumor cells via active targeting or Enhanced Permeability and Retention (EPR) effect. The combination of the TME control and therapeutic NPs offers promising solutions for improving the prognosis of the TNBC because the TME actively participates in tumor growth, metastasis, and drug resistance. The NP-based systems leverage stimulus-responsive mechanisms, such as low pH value, hypoxic, excessive secretion enzyme, concentration of glutathione (GSH)/reactive oxygen species (ROS), and high concentration of Adenosine triphosphate (ATP) to combat TNBC progression. Concurrently, NP-based stimulus-responsive introduces a novel approach for drug dosage design, administration, and modification of the pharmacokinetics of conventional chemotherapy and immunotherapy drugs. This review provides a comprehensive examination of the strengths, limitations, applications, perspectives, and future expectations of both novel and traditional stimulus-responsive NP-based drug delivery systems for improving outcomes in the medical practice of TNBC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Antineoplásicos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Sistemas de Liberação de Fármacos por Nanopartículas , Sistemas de Liberação de Medicamentos , Nanomedicina , Microambiente Tumoral , Nanopartículas/uso terapêutico
12.
Phytomedicine ; 128: 155521, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489891

RESUMO

BACKGROUND: The ancient Chinese herb Salvia miltiorrhiza Bunge (Danshen), plays the important role in cardiovascular and cerebrovascular disease. Furthermore, Danshen could also be used for curing carcinogenesis. Up to now, the anti-tumor effects of the main active constituents of Danshen have made great progress. However, the bioavailability of the active constituents of Danshen were restricted by their unique physical characteristics, like low oral bioavailability, rapid degradation in vivo and so on. PURPOSE: With the leap development of nano-delivery systems, the shortcomings of the active constituents of Danshen have been greatly ameliorated. This review tried to summarize the recent progress of the active constituents of Danshen based delivery systems used for anti-tumor therapeutics. METHODS: A systematic literature search was conducted using 5 databases (Embase, Google scholar, PubMed, Scopus and Web of Science databases) for the identification of relevant data published before September 2023. The words "Danshen", "Salvia miltiorrhiza", "Tanshinone", "Salvianolic acid", "Rosmarinic acid", "tumor", "delivery", "nanomedicine" and other active ingredients contained in Danshen were searched in the above databases to gather information about pharmaceutical decoration for the active constituents of Danshen used for anti-tumor therapeutics. RESULTS: The main extracts of Danshen could inhibit the proliferation of tumor cells effectively and a great deal of studies were conducted to design drug delivery systems to ameliorate the anti-tumor effect of the active contents of Danshen through different ways, like improving bioavailability, increasing tumor targeting ability, enhancing biological barrier permeability and co-delivering with other active agents. CONCLUSION: This review systematically represented recent progress of pharmaceutical decorations for the active constituents of Danshen used for anti-tumor therapeutics, revealing the diversity of nano-decoration skills and trying to inspire more designs of Danshen based nanodelivery systems, with the hope that bringing the nanomedicine of the active constituents of Danshen for anti-tumor therapeutics from bench to bedside in the near future.


Assuntos
Antineoplásicos Fitogênicos , Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Humanos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Sistemas de Liberação de Medicamentos , Animais , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Nanopartículas/química
13.
Acta Biomater ; 177: 456-471, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38331131

RESUMO

Cetuximab (Cet) and oxaliplatin (OXA) are used as first-line drugs for patients with colorectal carcinoma (CRC). In fact, the heterogeneity of CRC, mainly caused by K-ras mutations and drug resistance, undermines the effectiveness of drugs. Recently, a hydrophobic prodrug, (1E,4E)-6-((S)-1-(isopentyloxy)-4-methylpent-3-en-1-yl)-5,8-dimethoxynaphthalene-1,4­dione dioxime (DMAKO-20), has been shown to undergo tumor-specific CYP1B1-catalyzed bioactivation. This process results in the production of nitric oxide and active naphthoquinone mono-oximes, which exhibit specific antitumor activity against drug-resistant CRC. In this study, a Cet-conjugated bioresponsive DMAKO-20/PCL-PEOz-targeted nanocodelivery system (DMAKO@PCL-PEOz-Cet) was constructed to address the issue of DMAKO-20 dissolution and achieve multitargeted delivery of the cargoes to different subtypes of CRC cells to overcome K-ras mutations and drug resistance in CRC. The experimental results demonstrated that DMAKO@PCL-PEOz-Cet efficiently delivered DMAKO-20 to both K-ras mutant and wild-type CRC cells by targeting the epidermal growth factor receptor (EGFR). It exhibited a higher anticancer effect than OXA in K-ras mutant cells and drug-resistant cells. Additionally, it was observed that DMAKO@PCL-PEOz-Cet reduced the expression of glutathione peroxidase 4 (GPX4) in CRC cells and significantly inhibited the growth of heterogeneous HCT-116 subcutaneous tumors and patient-derived tumor xenografts (PDX) model tumors. This work provides a new strategy for the development of safe and effective approaches for treating CRC. STATEMENT OF SIGNIFICANCE: (1) Significance: This work reports a new approach for the treatment of colorectal carcinoma (CRC) using the bioresponsible Cet-conjugated PCL-PEOz/DMAKO-20 nanodelivery system (DMAKO@PCL-PEOz-Cet) prepared with Cet and PCL-PEOz for the targeted transfer of DMAKO-20, which is an anticancer multitarget drug that can even prevent drug resistance, to wild-type and K-ras mutant CRC cells. DMAKO@PCL-PEOz-Cet, in the form of nanocrystal micelles, maintained stability in peripheral blood and efficiently transported DMAKO-20 to various subtypes of colorectal carcinoma cells, overcoming the challenges posed by K-ras mutations and drug resistance. The system's secure and effective delivery capabilities have also been confirmed in organoid and PDX models. (2) This is the first report demonstrating that this approach simultaneously overcomes the K-ras mutation and drug resistance of CRC.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Humanos , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Sistemas de Liberação de Fármacos por Nanopartículas , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Mutação , Concentração de Íons de Hidrogênio
14.
Int J Oncol ; 64(4)2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38391039

RESUMO

Lung cancer represents a marked global public health concern. Despite existing treatment modalities, the average 5­year survival rate for patients with patients with lung cancer is only ~20%. As there are numerous adverse effects of systemic administration routes, there is an urgent need to develop a novel therapeutic strategy tailored specifically for patients with lung cancer. Non­invasive aerosol inhalation, as a route of drug administration, holds unique advantages in the context of respiratory diseases. Nanoscale materials have extensive applications in the field of biomedical research in recent years. The present study provides a comprehensive review of the classification, applications summarized according to existing clinical treatment modalities for lung cancer and challenges associated with inhalable micron/nanoparticle drug delivery systems (DDSs) in lung cancer. Achieving localized treatment of lung cancer preclinical models through inhalation is deemed feasible. However, further research is required to substantiate the efficacy and long­term safety of inhalable micron/nanoparticle DDSs in the clinical management of lung cancer.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias Pulmonares , Humanos , Administração por Inalação , Sistemas de Liberação de Medicamentos , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas
15.
Food Res Int ; 180: 114068, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38395544

RESUMO

Gallic acid (GA), a dietary phenolic acid with potent antioxidant activity, is widely distributed in edible plants. GA has been applied in the food industry as an antimicrobial agent, food fresh-keeping agent, oil stabilizer, active food wrap material, and food processing stabilizer. GA is a potential dietary supplement due to its health benefits on various functional disorders associated with oxidative stress, including renal, neurological, hepatic, pulmonary, reproductive, and cardiovascular diseases. GA is rapidly absorbed and metabolized after oral administration, resulting in low bioavailability, which is susceptible to various factors, such as intestinal microbiota, transporters, and metabolism of galloyl derivatives. GA exhibits a tendency to distribute primarily to the kidney, liver, heart, and brain. A total of 37 metabolites of GA has been identified, and decarboxylation and dihydroxylation in phase I metabolism and sulfation, glucuronidation, and methylation in phase Ⅱ metabolism are considered the main in vivo biotransformation pathways of GA. Different types of nanocarriers, such as polymeric nanoparticles, dendrimers, and nanodots, have been successfully developed to enhance the health-promoting function of GA by increasing bioavailability. GA may induce drug interactions with conventional drugs, such as hydroxyurea, linagliptin, and diltiazem, due to its inhibitory effects on metabolic enzymes, including cytochrome P450 3A4 and 2D6, and transporters, including P-glycoprotein, breast cancer resistance protein, and organic anion-transporting polypeptide 1B3. In conclusion, in-depth studies of GA on food industry applications, health benefits, bioavailability, nano-delivery systems, and drug interactions have laid the foundation for its comprehensive application as a food additive and dietary supplement.


Assuntos
Antioxidantes , Ácido Gálico , Antioxidantes/farmacologia , Ácido Gálico/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Disponibilidade Biológica , Sistemas de Liberação de Fármacos por Nanopartículas , Proteínas de Neoplasias/metabolismo , Interações Medicamentosas , Proteínas de Membrana Transportadoras/metabolismo , Indústria Alimentícia
16.
Int J Pharm ; 653: 123840, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38262585

RESUMO

Inflammation of the posterior segment of the eye is a severe condition and hard to cure as delivery of drugs to the inflammation site is inefficient. Currently, the primary treatment approach is ocular surgery or invasive ocular injections. Herein, we designed and developed a topically self nano-emulsifying drug delivery system (SNEDDs) to deliver triamcinolone acetonide (TCA) to the posterior segment of the eye. A screening based on TCA solubility was conducted on each excipient followed by preparation of various formulations using different ratios of the selected excipients. Vesicles of optimized SNEDDs had less than 100 nm size and spherical morphology. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay showed self-emulsified vesicles have relatively high safety on retinal pigment epithelium (RPE) cell line. Furthermore, efficient cellular uptake of coumarin 6-loaded SNEDDs in RPE using confocal laser scanning microscopy (CLSM) was confirmed. In addition, an in-vivo study using hematoxylin and eosin (H&E) staining revealed that 14 days of topical treatment of albino rabbit eyes with TCA-loaded SNEDDs was safe and no sign of tissue destruction and inflammation was detected in different parts of the eye sections including cornea, sclera, retina, and optic nerve. Also, the CLSM images from topically treated eyes with coumarin 6 (a hydrophobic, fluorescent drug model) loaded SNEDDs, showed that the optimized SNEDDs could properly penetrate toward the posterior segments of the eye especially the retina, posterior parts of the choroid, and sclera. Considering the outstanding results obtained by ocular tissue penetration and low toxicity, prepared SNEDDs, have the potential to be used as a topical administration for treating posterior segment disorders of the eye through an utterly non-invasive route and TCA-loaded SNEDDs could be an alternative for TCA intravitreal and intra conjunctival injections.


Assuntos
Cumarínicos , Sistemas de Liberação de Medicamentos , Oftalmologia , Tiazóis , Animais , Coelhos , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Fármacos por Nanopartículas , Triancinolona Acetonida , Preparações Farmacêuticas , Solubilidade , Excipientes , Inflamação , Emulsões/química
17.
Nanotechnology ; 35(13)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38198449

RESUMO

Chemotherapy is an important cancer treatment modality, but the clinical utility of chemotherapeutics is limited by their toxic side effects, inadequate distribution and insufficient intracellular concentrations. Nanodrug delivery systems (NDDSs) have shown significant advantages in cancer diagnosis and treatment. Variable NDDSs that respond to endogenous and exogenous triggers have attracted much research interest. Here, we summarized nanomaterials commonly used for tumor therapy, such as peptides, liposomes, and carbon nanotubes, as well as the responses of NDDSs to pH, enzymes, magnetic fields, light, and multiple stimuli. Specifically, well-designed NDDSs can change in size or morphology or rupture when induced by one or more stimuli. The varying responses of NDDSs to stimulation contribute to the molecular design and development of novel NDDSs, providing new ideas for improving drug penetration and accumulation, inhibiting tumor resistance and metastasis, and enhancing immunotherapy.


Assuntos
Nanopartículas , Nanotubos de Carbono , Neoplasias , Humanos , Imunoterapia , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas
18.
Biomolecules ; 14(1)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38254683

RESUMO

Advances in nanotechnology have provided novel avenues for the diagnosis and treatment of multiple myeloma (MM), a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow. This review elucidates the potential of nanotechnology to revolutionize myeloma therapy, focusing on nanoparticle-based drug delivery systems, nanoscale imaging techniques, and nano-immunotherapy. Nanoparticle-based drug delivery systems offer enhanced drug targeting, reduced systemic toxicity, and improved therapeutic efficacy. We discuss the latest developments in nanocarriers, such as liposomes, polymeric nanoparticles, and inorganic nanoparticles, used for the delivery of chemotherapeutic agents, siRNA, and miRNA in MM treatment. We delve into nanoscale imaging techniques which provide spatial multi-omic data, offering a holistic view of the tumor microenvironment. This spatial resolution can help decipher the complex interplay between cancer cells and their surrounding environment, facilitating the development of highly targeted therapies. Lastly, we explore the burgeoning field of nano-immunotherapy, which employs nanoparticles to modulate the immune system for myeloma treatment. Specifically, we consider how nanoparticles can be used to deliver tumor antigens to antigen-presenting cells, thus enhancing the body's immune response against myeloma cells. In conclusion, nanotechnology holds great promise for improving the prognosis and quality of life of MM patients. However, several challenges remain, including the need for further preclinical and clinical trials to assess the safety and efficacy of these emerging strategies. Future research should also focus on developing personalized nanomedicine approaches, which could tailor treatments to individual patients based on their genetic and molecular profiles.


Assuntos
Neoplasias Hematológicas , MicroRNAs , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Qualidade de Vida , Imunoterapia , Sistemas de Liberação de Fármacos por Nanopartículas , Microambiente Tumoral
19.
PeerJ ; 12: e16732, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38188167

RESUMO

Objective: This study aims to assess and compare the potential of advanced nano/micro delivery systems, including quantum dots, carbon nanotubes, magnetic nanoparticles, dendrimers, and microneedles, as theranostic platforms for oral cancer. Furthermore, we seek to evaluate their respective advantages and disadvantages over the past decade. Materials and Methods: A comprehensive literature search was performed using Google Scholar and PubMed, with a focus on articles published between 2013 and 2023. Search queries included the specific advanced delivery system as the primary term, followed by oral cancer as the secondary term (e.g., "quantum dots AND oral cancer," etc.). Results: The advanced delivery platforms exhibited notable diagnostic and therapeutic advantages when compared to conventional techniques or control groups. These benefits encompassed improved tumor detection and visualization, enhanced precision in targeting tumors with reduced harm to neighboring tissues, and improved drug solubility and distribution, leading to enhanced drug absorption and tumor uptake. Conclusion: The findings suggest that advanced nano/micro delivery platforms hold promise for addressing numerous challenges associated with chemotherapy. By enabling precise targeting of cancerous cells, these platforms have the potential to mitigate adverse effects on surrounding healthy tissues, thus encouraging the development of innovative diagnostic and therapeutic strategies for oral cancer.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias Bucais , Nanotubos de Carbono , Humanos , Medicina de Precisão , Neoplasias Bucais/diagnóstico , Transporte Biológico , Sistemas de Liberação de Fármacos por Nanopartículas
20.
J Drug Target ; 32(3): 311-324, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38269853

RESUMO

The boom in cancer immunotherapy has provided many patients with a better chance of survival, but opportunities often come with challenges. Single immunotherapy is not good enough to eradicate tumours, and often fails to achieve the desired therapeutic effect because of the low targeting of immunotherapy drugs, and causes more side effects. As a solution to this problem, researchers have developed several nano Drug Delivery Systems (NDDS) to deliver immunotherapeutic agents to achieve good therapeutic outcomes. However, traditional drug delivery systems (DDS) have disadvantages such as poor bioavailability, high cytotoxicity, and difficulty in synthesis, etc. Herbal Polysaccharides (HPS), derived from natural Chinese herbs, inherently possess low toxicity. Furthermore, the biocompatibility, biodegradability, hydrophilicity, ease of modification, and immunomodulatory activities of HPS offer unique advantages in substituting traditional DDS. This review initially addresses the current developments and challenges in immunotherapy. Subsequently, it focuses on the immunomodulatory mechanisms of HPS and their design as nanomedicines for targeted drug delivery in tumour immunotherapy. Our findings reveal that HPS-based nanomedicines exhibit significant potential in enhancing the efficacy of cancer immunotherapy, providing crucial theoretical foundations and practical guidelines for future clinical applications.


Assuntos
Sistemas de Liberação de Fármacos por Nanopartículas , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Imunoterapia , Neoplasias/tratamento farmacológico , Polissacarídeos
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