NUS Graduate School of Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, Singapore; Department of Biomedical Engineering, National University of Singapore, Singapore 117583, Singapore.
Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.
J Control Release. 2019 Apr 28;300:161-173. doi: 10.1016/j.jconrel.2019.02.041. Epub 2019 Mar 7.
Urine voiding and the presence of a mucus layer on the apical surface of the urothelium are two major challenges towards an effective intravesical drug delivery for bladder malignancies. Improved bioavailability to the underlying bladder tissue could be achieved with delivery vectors that diffuse efficiently through the bladder mucus. Pegylation of delivery vectors remains the existing "gold standard" to enhance mucosal delivery despite known poor cell uptake and reported PEG sensitivity. Here, we showed improved mucopenetration of carboxylated polystyrene (PS) nanoparticles (NPs) passivated with a polydopamine (PDA) surface, at similar level as PEG. While the diffusion of PS NPs in mucus was retarded by ~1000-fold, PS-PDA diffused only 6-fold slower in mucus than water. This enabled faster and deeper penetration of PS-PDA into porcine bladder tissue beneath the mucus layer. The same PDA surface also conferred biocompatibility and enabled photothermal therapy (PTT) with significant surface disruption on an ex vivo porcine bladder model upon localized laser irradiation, which was not possible with PEG. Our outcomes suggested the facile and versatile PDA surface passivation of nanoparticles as an enabler for dual purposes of enhancing mucopenetration and allowing photothermal therapy on bladder tissue, which has not been demonstrated to date.
尿液排空和尿路上皮顶表面的黏液层的存在是实现膀胱恶性肿瘤有效腔内药物输送的两个主要挑战。通过能够有效地扩散通过膀胱黏液的输送载体，可以实现对底层膀胱组织的改善生物利用度。尽管已知细胞摄取率低且报道了 PEG 敏感性，但 PEG 化输送载体仍然是增强黏膜输送的现有“金标准”。在这里，我们展示了用聚多巴胺（PDA）表面钝化的羧化聚苯乙烯（PS）纳米颗粒（NPs）的改进的黏液穿透性，其水平与 PEG 相似。虽然 PS NPs 在黏液中的扩散被延迟了约 1000 倍，但 PS-PDA 在黏液中的扩散速度仅比水慢 6 倍。这使得 PS-PDA 能够更快、更深地穿透黏液层下的猪膀胱组织。相同的 PDA 表面还赋予了生物相容性，并能够在局部激光照射下对离体猪膀胱模型进行光热治疗（PTT），而 PEG 则无法实现。我们的研究结果表明，简单且多功能的 PDA 表面可以钝化纳米颗粒，从而增强黏液穿透性，并允许对膀胱组织进行光热治疗，这是迄今为止尚未证明的。
