A minimally invasive, highly efficient and versatile strategy is proposed for localized tumor regression by developing a smart injectable liquid-solid phase-transformation organic-inorganic hybrid composite material, i.e., magnetic Fe powder-dispersed PLGA (Fe/PLGA) implants formagnetic-hyperthermiatherapy of cancer.
Cell-permeable peptides (CPPs) and ultrasound-targeted microbubble destruction (UTMD) have tremendous potential for gene delivery. However, their applications are limited due to nonspecificity of CPPs and low transfection efficiency of UTMD. Here, we developed a smart gene delivery system by encapsulating TAT peptide (TATp) and hepatocyte growth factor (HGF) gene within lipid microbubbles, in which TATp was protected from being enzymatically cleaved and HGF gene was protected from degradation. This new strategy had synergistic effects of UTMD and TATp on gene transfection. We investigated the efficacy and safety of HGF gene transfection mediated by the combination of UTMD and TATp in vitro and in vivo. The results from MTT assay and flow cytometry analyses indicated that the combination of UTMD and TATp could enhance HGF gene expression in HUVECs without any significant side effect on cell viability. In rat myocardial infarction models, we demonstrated that the protein and mRNA expressions of HGF in myocardium caused by the combination of UTMD and TATp were the highest. Histopathological findings demonstrated that the combination of UTMD and TATp enhanced myocardial microvasculature and ameliorated myocardial fibrosis. In conclusion, the combination of UTMD and TATp might be a safe and efficient technique for gene delivery.
Ultrasound targeted microbubble destruction (UTMD) was one of the most promising strategies to enhance drug delivery in cancer therapy. Microbubbles (MBs) serve as a vehicle to carry anti-tumor drugs and locally release them when exposed to therapeutic ultrasound, resulting in drug accumulation in tumor tissues and enhanced anti-tumor effect. However the ultrasound triggered drug delivery system has been seriously limited due to the poor loading capacity of MBs. Here we present a new strategy to overcome the low drug payload of MBs for ultrasound guided drug delivery. In this study, we developed a novel microbubble carrying 10-HCPT which only needs a particularly low single dose of injection (4-6 mg) for tumor therapy in clinical application, therefore, the required high dosing of drug loaded MBs for ultrasound mediated drug delivery is not necessary. We subsequently investigated the combination of ultrasound application with HLMs to achieve therapeutic effect on tumor at a feasible dose of MBs. HLMs were manufactured with a high drug encapsulation and loading content and simultaneously maintained the acoustic properties as an ultrasound contrast agent. After that, tumor-bearing mice were routinely and non-invasively administered with HLMs through the tail vein and were then exposed to ultrasound, resulting in a remarkable drug accumulation in tumor tissues and a significant increase in tumor inhibition rate (70.6%) compared with HLMs alone (47.8%) as well as commercial HCPT injection (49.4). In conclusion, HLMs are expected to improve the therapeutic efficacy of MBs and are worthy of further study for UTMD mediated drug delivery.
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