Gyawali Dipendra, Kim Jimin P, Yang Jian
Department of Bioengineering, The University of Texas at Arlington, Arlington, TX 76010.
Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA 16802.
Bioact Mater. 2018 Mar;3(1):39-47. doi: 10.1016/j.bioactmat.2017.03.001. Epub 2017 Mar 27.
A novel photo-crosslinkable nanogel is prepared from a biodegradable polymer template with intrinsic photoluminescence and high photostability. The fluorescent nanogels display excellent biodegradability and cytocompatibility owed to the facile synthesis scheme involving a solvent-and surfactant-free one-pot reaction, derived entirely from biocompatible monomers citric acid, maleic acid, L-cysteine, and poly(ethylene glycol). The resultant nanogels are less than 200 nm in diameter with a narrow size distribution and monodispersity, and demonstrate long-term structural stability in biological buffer for two weeks. To gauge potential in theranostic applications, the fluorescent nanogels were surface functionalized with biologically active RGD peptides and encapsulated with active anti-cancer drug Doxorubicin, resulting in a pH-responsive controlled drug release in acidic pH resembling tumor environments. The strong fluorescence of the nanogels enabled tracking of targeted drug delivery, showing that drug-loaded nanogels homed into the cytoplasmic regions of prostate cancer cells to significantly induce cell death. These photo-crosslinkable and biodegradable nanogels pose as a strong candidate for theranostic medicine, demonstrating versatile functionalization, high stability in biological buffers, and capacity for real-time fluorescence-based monitoring of targeted drug delivery.
一种新型的可光交联纳米凝胶由具有固有光致发光和高光稳定性的可生物降解聚合物模板制备而成。这些荧光纳米凝胶具有出色的生物降解性和细胞相容性,这得益于其简便的合成方案,该方案涉及无溶剂和无表面活性剂的一锅法反应,完全由生物相容性单体柠檬酸、马来酸、L-半胱氨酸和聚乙二醇制成。所得纳米凝胶的直径小于200 nm,尺寸分布窄且具有单分散性,并在生物缓冲液中表现出长达两周的长期结构稳定性。为了评估其在治疗诊断应用中的潜力,对荧光纳米凝胶进行了表面功能化,使其带有生物活性RGD肽,并包裹了活性抗癌药物阿霉素,从而在类似于肿瘤环境的酸性pH值下实现了pH响应控制的药物释放。纳米凝胶的强荧光能够追踪靶向药物递送,表明载药纳米凝胶归巢到前列腺癌细胞的细胞质区域,从而显著诱导细胞死亡。这些可光交联且可生物降解的纳米凝胶是治疗诊断医学的有力候选者,展示了多功能功能化、在生物缓冲液中的高稳定性以及基于实时荧光监测靶向药物递送的能力。