Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 USA.
Nanotheranostics. 2021 Apr 27;5(4):417-430. doi: 10.7150/ntno.59568. eCollection 2021.
Delivery of long-acting nanoformulated antiretroviral drugs (ARVs) to human immunodeficiency virus type one cell and tissue reservoirs underlies next generation antiretroviral therapeutics. Nanotheranostics, comprised of trackable nanoparticle adjuncts, can facilitate ARV delivery through real-time drug tracking made possible through bioimaging platforms. To model HIV-1 therapeutic delivery, europium sulfide (EuS) nanoprobes were developed, characterized and then deployed to cells, tissues, and rodents. Tests were performed with nanoformulated rilpivirine (NRPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used clinically to suppress or prevent HIV-1 infection. , CD4+ T cells and monocyte-derived macrophages were EuS-treated with and without endocytic blockers to identify nanoprobe uptake into cells. , Balb/c mice were co-dosed with NRPV and EuS or lutetium-doped EuS (LuEuS) theranostic nanoparticles to assess NRPV biodistribution via mass spectrometry. , single photon emission computed tomography (SPECT-CT) and magnetic resonance imaging (MRI) bioimaging were used to determine nanotheranostic and NRPV anatomic redistribution over time. EuS nanoprobes and NRPV entered cells through dynamin-dependent pathways. SPECT-CT and MRI identified biodistribution patterns within the reticuloendothelial system for EuS that was coordinate with NRPV trafficking. EuS nanoprobes parallel the uptake and biodistribution of NRPV. These data support their use in modeling NRPV delivery to improve treatment strategies.
长效纳米剂型抗逆转录病毒药物(ARV)递送至人类免疫缺陷病毒 1 型细胞和组织储库是下一代抗逆转录病毒治疗的基础。由可追踪的纳米颗粒辅助剂组成的纳米治疗学可以通过生物成像平台实现的实时药物跟踪来促进 ARV 递送至细胞中。为了模拟 HIV-1 治疗性递药,开发、表征了硫化铕(EuS)纳米探针,然后将其递送至细胞、组织和啮齿动物中。用纳米剂型利匹韦林(NRPV)进行了测试,NRPV 是一种临床上用于抑制或预防 HIV-1 感染的非核苷类逆转录酶抑制剂(NNRTI)。用和不用内吞阻滞剂处理 CD4+T 细胞和单核细胞衍生的巨噬细胞,以鉴定纳米探针进入细胞的摄取情况。用 NRPV 和 EuS 或掺镥的 EuS(LuEuS)治疗性纳米颗粒对 Balb/c 小鼠进行共给药,通过质谱法评估 NRPV 的生物分布。单光子发射计算机断层扫描(SPECT-CT)和磁共振成像(MRI)生物成像用于确定纳米治疗剂和 NRPV 在一段时间内的解剖再分布。EuS 纳米探针和 NRPV 通过依赖于胞吞作用的途径进入细胞。SPECT-CT 和 MRI 确定了 EuS 在网状内皮系统中的生物分布模式,与 NRPV 的转运相协调。EuS 纳米探针与 NRPV 的摄取和生物分布平行。这些数据支持将其用于模拟 NRPV 递药以改善治疗策略。