Kona Soujanya, Specht Danyel, Rahimi Maham, Shah Bhavik P, Gilbertson Timothy A, Nguyen Kytai T
Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA.
J Nanosci Nanotechnol. 2012 Jan;12(1):236-44. doi: 10.1166/jnn.2012.5131.
Targeted delivery of therapeutic agents to prevent smooth muscle cell (SMC) proliferation is important in averting restenosis (a narrowing of blood vessels). Since platelet derived growth factor (PDGF) receptors are over-expressed in proliferating SMCs after injury from cardiovascular interventions, such as angioplasty and stent implantation, our hypothesis is that conjugation of PDGF-BB (platelet-derived growth factor BB (homodimer)) peptides to biodegradable poly (D,L-lactic-co-glycolide) (PLGA) nanoparticles (NPs) would exhibit an increased uptake of these NPs by proliferating SMCs. In this study, poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles containing dexamethasone were formulated and conjugated with PDGF-BB peptides. These NPs were stable, biocompatible, and exhibited a sustained drug release over 14 days. Various particle uptake studies using HASMCs (human aortic smooth muscle cells) demonstrated that PDGF-BB peptide-conjugated nanoparticles significantly increased cellular uptake and decreased proliferation of HASMCs compared to control nanoparticles (without conjugation of PDGF-BB peptides). These NPs were internalized primarily by clathrin-mediated endocytosis and macropinocytosis. Our in vitro results suggest that PDGF-BB peptide-conjugated NPs could represent as an effective targeted, sustained therapeutic delivery system to reduce restenosis and neointimal hyperplasia.
将治疗剂靶向递送至平滑肌细胞（SMC）以防止其增殖，对于避免血管再狭窄（血管变窄）至关重要。由于血小板衍生生长因子（PDGF）受体在诸如血管成形术和支架植入等心血管介入损伤后增殖的SMC中过度表达，我们的假设是将PDGF-BB（血小板衍生生长因子BB（同二聚体））肽与可生物降解的聚（D，L-丙交酯-共-乙交酯）（PLGA）纳米颗粒（NPs）偶联，会使增殖的SMC对这些NPs的摄取增加。在本研究中，制备了含有地塞米松的聚（D，L-丙交酯-共-乙交酯）（PLGA）纳米颗粒，并与PDGF-BB肽偶联。这些NPs稳定、具有生物相容性，并在14天内呈现持续的药物释放。使用人主动脉平滑肌细胞（HASMCs）进行的各种颗粒摄取研究表明，与对照纳米颗粒（未偶联PDGF-BB肽）相比，偶联了PDGF-BB肽的纳米颗粒显著增加了细胞摄取并降低了HASMCs的增殖。这些NPs主要通过网格蛋白介导的内吞作用和巨胞饮作用被内化。我们的体外研究结果表明，偶联了PDGF-BB肽的NPs可作为一种有效的靶向、持续治疗递送系统，以减少血管再狭窄和内膜增生。
