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1.
Life Sci ; 346: 122629, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631667

RESUMO

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.


Assuntos
Ferroptose , Nanoestruturas , Neoplasias , Ferroptose/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Animais , Simulação de Dinâmica Molecular , Ferro/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
2.
Int J Pharm ; 642: 123144, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37330155

RESUMO

Oral cancer accounts for more than 350,000 cases worldwide with 90% of them being oral squamous cell carcinomas (OSCC). The current treatment modalities of chemoradiation have poor outcomes along with harmful effects to neighbouring healthy tissues. The present study aimed to deliver Erlotinib (ERB), locally at the site of tumor arising in the oral cavity. ERB was encapsulated in liposomal formulations (ERB Lipo) and optimized using full factorial, 32 experimental design. The optimized batch was then coated with chitosan to obtain CS-ERB Lipo and were characterized further. Both liposomal ERB formulations had size <200 nm and PDI < 0.4. Zeta potential was upto -50 mV for ERB Lipo and upto +25 mV for CS-ERB Lipo indicating stable formulation. Liposomal formulations were freeze dried and loaded into gel to study in-vitro release and chemotherapeutic evaluation. CS-ERB Lipo showed sustained release upto 36 h from gel as compared to control formulation. In-vitro cell viability studies showed potent anti-cancer activity on KB-cells. In-vivo studies showed better pharmacological efficacy in terms of tumor volume reduction for ERB Lipo gel (49.19%) and CS-ERB Lipo gel (55.27%) as compared to plain ERB Gel (38.88%) applied locally. Histology also revealed that formulation could alleviate dysplasia condition to hyperplasia. The locoregional therapy of ERB Lipo gel and CS-ERB Lipo gel thus show promising outcome in improving pre-malignant and early-stage oral cavity cancers.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Cloridrato de Erlotinib , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/tratamento farmacológico , Lipossomos
3.
J Control Release ; 350: 538-568, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36030993

RESUMO

The invigoration of protein and peptides in serious eye disease includes age-related macular degeneration, choroidal neovascularization, retinal neovascularization, and diabetic retinopathy. The transportation of macromolecules like aptamers, recombinant proteins, and monoclonal antibodies to the posterior segment of the eye is challenging due to their high molecular weight, rapid degradation, and low solubility. Moreover, it requires frequent administration for prolonged therapy. The long-acting novel formulation strategies are helpful to overcome these issues and provide superior therapy. It avoids frequent administration, improves stability, high retention time, and avoids burst release. This review briefly enlightens posterior segments of eye diseases with their diagnosis techniques and treatments. This article mainly focuses on recent advanced approaches like intravitreal implants and injectables, electrospun injectables, 3D printed drug-loaded implants, nanostructure thin-film polymer devices encapsulated cell technology-based intravitreal implants, injectable and depots, microneedles, PDS with ranibizumab, polymer nanoparticles, inorganic nanoparticles, hydrogels and microparticles for delivering macromolecules in the eye for intended therapy. Furthermore, novel techniques like aptamer, small Interference RNA, and stem cell therapy were also discussed. It is predicted that these systems will make revolutionary changes in treating posterior segment eye diseases in future.


Assuntos
Oftalmopatias , Ranibizumab , Sistemas de Liberação de Medicamentos/métodos , Oftalmopatias/tratamento farmacológico , Humanos , Hidrogéis/uso terapêutico , Injeções Intravítreas , Peptídeos/uso terapêutico , Polímeros/uso terapêutico , RNA , Ranibizumab/uso terapêutico , Proteínas Recombinantes/uso terapêutico
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