RESUMEN
Rebuilding of infarcted myocardium by mesenchymal stem cells (MSCs) has not been successful because of poor cell survival due in part to insufficient blood supply after myocardial infarction (MI). We hypothesize that targeted delivery of vascular endothelial growth factor (VEGF) to MI can help regenerate vasculature in support of MSC therapy in a rat model of MI. VEGF-encapsulated immunoliposomes targeting overexpressed P-selectin in MI tissue were infused by tail vein immediately after MI. One week later, MSCs were injected intramyocardially. The cardiac function loss was moderated slightly by targeted delivery of VEGF or MSC treatment. Targeted VEGF+MSC combination treatment showed highest attenuation in cardiac function loss. The combination treatment also increased blood vessel density (80%) and decreased collagen content in post-MI tissue (33%). Engraftment of MSCs in the combination treatment group was significantly increased and the engrafted cells contributed to the restoration of blood vessels. FROM THE CLINICAL EDITOR: VEGF immunoliposomes targeting myocardial infarction tissue resulted in significantly higher attenuation of cardiac function loss when used in combination with mesenchymal stem cells. MSCs were previously found to have poor ability to restore cardiac tissue, likely as a result of poor blood supply in the affected areas. This new method counterbalances that weakness by the known effects of VEGF, as demonstrated in a rat model.
Asunto(s)
Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/terapia , Factor A de Crecimiento Endotelial Vascular/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Animales , Vasos Sanguíneos/efectos de los fármacos , Colágeno/metabolismo , Modelos Animales de Enfermedad , Trasplante de Células Madre Mesenquimatosas , RatasRESUMEN
Noninvasive injection of pro-angiogenic compounds such as vascular endothelial growth factor (VEGF) has shown promising results in regenerating cardiac microvasculature. However, these results have failed to translate into successful clinical trials in part due to the short half-life of VEGF in circulation. Increasing the dose of VEGF may increase its availability to the target tissue, but harmful side-effects remain a concern. Encapsulating and selectively targeting VEGF to the MI border zone may circumvent these problems. Anti-P-selectin conjugated immunoliposomes containing VEGF were developed to target the infarct border zone in a rat MI model. Targeted VEGF therapy significantly improves vascularization and cardiac function after an infarction.
Asunto(s)
Sistemas de Liberación de Medicamentos , Corazón/efectos de los fármacos , Liposomas , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/fisiopatología , Selectina-P/metabolismo , Factor A de Crecimiento Endotelial Vascular/administración & dosificación , Animales , Semivida , Humanos , Masculino , Neovascularización Patológica/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/farmacologíaRESUMEN
IMPORTANCE OF THE FIELD: Significant improvements in breast cancer treatments have resulted in a significant decrease in mortality. However, current breast cancer therapies, for example, chemotherapy, often result in high toxicity and nonspecific side effects. Other treatments, such as hormonal and antiangiogenic therapies, often have low treatment efficacy if used alone. In addition, acquired drug resistance decreases further the treatment efficacy of these therapies. Intra-tumor heterogeneity of the tumor tissue may be a major reason for the low treatment efficacy and the development of chemoresistance. Therefore, targeted multi-drug therapy is a valuable option for addressing the multiple mechanisms that may be responsible for reduced efficacy of current therapies. AREAS COVERED IN THIS REVIEW: In this article, different classes of drugs for treating breast cancer, the possible reasons for the drug resistance in breast cancer, as well as different targeted drug delivery systems are summarized. The current targeting strategies used in cancer treatment are discussed. WHAT THE READER WILL GAIN: This article considers the current state of breast cancer therapy and the possible future directions in targeted multi-drug delivery for treating breast cancer. TAKE HOME MESSAGE: A better understanding of tumor biology and physiological responses to nanoparticles, as well as advanced nanoparticle design, are needed to improve the therapeutic outcomes for treating breast cancer using nanoparticle-based targeted drug delivery systems. Moreover, selective delivery of multi-drugs to tumor tissue using targeted drug delivery systems may reduce systemic toxicity further, overcome drug resistances, and improve therapeutic efficacy in treating breast cancer.