RESUMEN
Combination chemotherapy, which involves the simultaneous use of multiple anticancer drugs in adequate combinations to disrupt multiple mechanisms associated with tumor growth, has shown advantages in enhanced therapeutic efficacy and lower systemic toxicity relative to monotherapy. Herein, we employed coordination-driven self-assembly to construct discrete Pt(II) metallacycles as monodisperse, modular platforms for combining camptothecin and combretastatin A4, two chemotherapy agents with a disparate mechanism of action, in precise arrangements for combination chemotherapy. Formulation of the drug-loaded metallacycles with folic acidfunctionalized amphiphilic diblock copolymers furnished nanoparticles with good solubility and stability in physiological conditions. Folic acids on the surface of the nanoparticles promote their internalization into cancer cells. The intracellular reductive environment of cancer cells induces the release of the drug molecules at an exact 1:1 ratio, leading to a synergistic anticancer efficacy. In vivo studies on tumor-bearing mice demonstrated the favorable therapeutic outcome and minimal side effects of the combination chemotherapy approach based on a self-assembled metallacycle.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina , Neoplasias , Platino (Metal) , Estilbenos , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/química , Camptotecina/administración & dosificación , Camptotecina/farmacología , Liberación de Fármacos , Sinergismo Farmacológico , Ácido Fólico/química , Humanos , Ratones , Nanopartículas , Neoplasias/tratamiento farmacológico , Platino (Metal)/química , Polímeros/uso terapéutico , Estilbenos/administración & dosificación , Estilbenos/farmacología , Microambiente TumoralRESUMEN
RNA interference (RNAi) gene silencing technologies have shown significant potential for treating various diseases, including cancer. However, clinical success in cancer therapy remains elusive, mainly owing to suboptimal inâ vivo delivery of RNAi therapeutics such as small interference RNA (siRNA) to tumors. Herein, we developed a library of polymers that respond to a narrow pH change (ultra-pH-responsive), and demonstrated the utility of these materials in targeted and deep tumor-penetrating nanoparticle (NP) for inâ vivo RNAi. The new NP platform is mainly composed of the following key components: i)â internalizing RGD (iRGD) to enhance tumor targeting and tissue penetration; ii)â polyethylene glycol (PEG) chains to prolong blood circulation; and iii)â sharp pH-responsive hydrophobic polymer to improve endosome escape. Through systematic studies of structure-function relationship, the optimized RNAi NPs (<70â nm) showed efficient gene silencing and significant inhibition of tumor growth with negligible toxicities inâ vivo.
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Preparaciones de Acción Retardada/química , Técnicas de Transferencia de Gen , Nanopartículas/química , Neoplasias/terapia , ARN Interferente Pequeño/administración & dosificación , Tratamiento con ARN de Interferencia/métodos , Línea Celular Tumoral , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Proteínas Inhibidoras de la Apoptosis/genética , Neoplasias/genética , Oligopéptidos/química , Polietilenglicoles/química , Polímeros/química , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacocinética , ARN Interferente Pequeño/uso terapéutico , SurvivinRESUMEN
Objective: To review the research progress of magnesium and magnesium alloy implants in the repair and reconstruction of sports injury. Methods: Relevant literature of magnesium and magnesium alloys for sports injury repair and reconstruction was extensively reviewed. The characteristics of magnesium and its alloys and their applications in the repair and reconstruction of sports injuries across various anatomical sites were thoroughly discussed and summarized. Results: Magnesium and magnesium alloys have advantages in mechanical properties, biosafety, and promoting tendon-bone interface healing. Many preclinical studies on magnesium and magnesium alloy implants for repairing and reconstructing sports injuries have yielded promising results. However, successful clinical translation still requires addressing issues related to mechanical strength and degradation behavior, where alloying and surface treatments offer feasible solutions. Conclusion: The clinical translation of magnesium and magnesium alloy implants for repairing and reconstructing sports injuries holds promise. Subsequent efforts should focus on optimizing the mechanical strength and degradation behavior of magnesium and magnesium alloy implants. Conducting larger-scale biocompatibility testing and developing novel magnesium-containing implants represent new directions for future research.
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Traumatismos en Atletas , Medicina Deportiva , Humanos , Magnesio , Aleaciones , Prótesis e Implantes , Ensayo de Materiales , Implantes Absorbibles , CorrosiónAsunto(s)
Indoles/química , Polímeros/química , Animales , Técnicas Biosensibles , Suministros de Energía Eléctrica , Humanos , Indoles/síntesis química , Indoles/farmacología , Indoles/uso terapéutico , Polímeros/síntesis química , Polímeros/farmacología , Polímeros/uso terapéutico , Purificación del AguaRESUMEN
The application of nanoparticles (NPs) to drug delivery has led to the development of novel nanotherapeutics for the treatment of various diseases including cancer. However, clinical use of NP-mediated drug delivery has not always translated into improved survival of cancer patients, in part due to the suboptimal properties of NP platforms, such as premature drug leakage during preparation, storage, or blood circulation, lack of active targeting to tumor tissue and cells, and poor tissue penetration. Herein, an innovative reactive oxygen species (ROS)-responsive polyprodrug is reported that can self-assemble into stable NPs with high drug loading. This new NP platform is composed of the following key components: (i) polyprodrug inner core that can respond to ROS for triggered release of intact therapeutic molecules, (ii) polyethylene glycol (PEG) outer shell to prolong blood circulation; and (iii) surface-encoded internalizing RGD (iRGD) to enhance tumor targeting and tissue penetration. These targeted ROS-responsive polyprodrug NPs show significant inhibition of tumor cell growth both in vitro and in vivo.
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Nanopartículas , Sistemas de Liberación de Medicamentos , Humanos , Neoplasias , Polietilenglicoles , Especies Reactivas de OxígenoRESUMEN
A novel blended nanoparticle (NP) system for the delivery of anticancer drugs and its surprisingly high efficacy for cancer chemotherapy by blending a targeting polymer folic acid-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (FA-PEG-b-PLGA) and a miscible structurally similar polymer D-α-tocopheryl polyethylene glycol 1000 succinate-poly(lactide-co-glycolide) (TPGS-PLGA) is reported. This blended NP system can be achieved through a simple and effective nanoprecipitation technique, and possesses unique properties: i) improved long-term compatibility brought by PEG-based polymers; ii) reduced multidrug resistance mediated by P-glycoprotein (P-gp) in tumor cells and increased bioavailability of anticancer drugs by incorporation of TPGS; iii) the regulation of controlled release through polymer ratios and active targeting by FA. Both in vitro cell experiments and in vivo antitumor assays demonstrated the reported blended NP system can achieve the best therapeutic efficiency in an extremely safe, simple and highly efficient process for cancer therapy. Moreover, this NP system is highly efficient in forming NPs with multiple functions, without repeated chemical modification of polymers, which is sometimes complex, inefficient and high cost. Therefore, the development of this novel blended NP concept is extremely meaningful for the application of pharmaceutical nanotechnology in recent studies.