Huang Chiung-Yi, Lin Shu-Yu, Hsu Tsu-An, Hsieh Hsing-Pang, Huang Ming-Hsi
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 350, Taiwan.
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan.
Nanomaterials (Basel). 2021 Jul 16;11(7):1844. doi: 10.3390/nano11071844.
Integrative medicine comprising a tumor-associated antigen vaccine and chemotherapeutic regimens has provided new insights into cancer therapy. In this study, the AB-type diblock copolymers poly(ethylene glycol)-polylactide (PEG-PLA) were subjected to the dispersion of poorly water-soluble molecules in aqueous solutions. The physicochemical behavior of the chemotherapeutic agent DBPR114 in the PEG-PLA-polymeric aqueous solution was investigated by dynamic light scattering (DLS) technology. In vitro cell culture indicated that replacing the organic solvent DMSO with PEG-PLA polymeric micelles could maintain the anti-proliferative effect of DBPR114 on leukemia cell lines. A murine tumor-associated antigen vaccine model was established in tumor-bearing mice to determine the effectiveness of these formulas in inducing tumor regression. The results demonstrated that the therapeutic treatments effectively reinforced each other via co-delivery of antitumor drug/antigen agents to synergistically integrate the efficacy of cancer therapy. Our findings support the potential use of polymeric micellar systems for aqueous solubilization and expansion of antitumor activity intrinsic to DBPR114 and tumor-associated antigen therapy.
包含肿瘤相关抗原疫苗和化疗方案的整合医学为癌症治疗提供了新的见解。在本研究中,AB型二嵌段共聚物聚(乙二醇)-聚丙交酯(PEG-PLA)用于使难溶性分子分散于水溶液中。采用动态光散射(DLS)技术研究了化疗药物DBPR114在PEG-PLA聚合物水溶液中的物理化学行为。体外细胞培养表明,用PEG-PLA聚合物胶束替代有机溶剂二甲基亚砜(DMSO)可维持DBPR114对白血病细胞系的抗增殖作用。在荷瘤小鼠中建立了鼠肿瘤相关抗原疫苗模型,以确定这些配方在诱导肿瘤消退方面的有效性。结果表明,通过共同递送抗肿瘤药物/抗原剂,治疗方法有效地相互增强,从而协同整合癌症治疗的疗效。我们的研究结果支持了聚合物胶束系统在水性增溶以及扩大DBPR114和肿瘤相关抗原疗法固有抗肿瘤活性方面的潜在应用。