Abstract：
Combination therapy using chemo-photothermal therapy (chemo-PTT) shows great efficacy toward tumor ablation in preclinical studies. Besides, lipopolymersomes as a hybrid nanocarriers, integrate advantages of liposomes and polymersomes in a single platform in order to provide tremendous biocompatibility, biodegradability, noteworthy loading efficacy for both hydrophobic and hydrophilic drugs with adjustable drug release and high stability. In this study, a multipurpose lipopolymersome was fabricated for guided chemotherapy-PTT and NIR-imaging of melanoma. A lipopolymerosomal hybrid nanovesicle consisting of equal molar ratio of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) diblock copolymer (molar ratio 1:1) was fabricated. The nanoparticulate system was prepared through film rehydration technique for encapsulation of doxorubicin (DOX) and indocyanine green (ICG) to form DOX-ICG-LP platform. At the next stage, AS1411 DNA aptamer was conjugated to the surface of lipopolymersome (Apt-DOX-ICG-LP) for selective delivery. The sizes of DOX-ICG-LP and Apt-DOX-ICG-LP were obtained through DLS analysis (61.0 ± 6 and 74 ± 5, respectively). Near Infrared-responsive release pattern of the prepared lipopolymersome was verified in vitro. The formulated platform showed efficient photothermal conversion, and superior stability with acceptable encapsulation efficiency. Consistent with the in vitro studies, NIR-responsive lipopolymersome exhibited significantly higher cellular toxicity for Chemo-PTT versus single anti-cancer treatment. Moreover, superlative tumor shrinkage with favorable survival profile were attained in B16F10 tumor-bearing mice received Apt-DOX-ICG-LP and irradiated with 808 nm laser compared to those treated with either DOX-ICG-LP or Apt-DOX-ICG-LP without laser irradiation. The diagnostic capability of Apt-DOX-ICG-LP was addressed using in vivo NIR imaging, 6 and 24 h post-intravenous administration. The results indicated desirable feature of an established targeted theranostic capability of Apt-DOX-ICG-LP for both diagnostics and dual chemo-PTT of melanoma.
摘要：
在临床前研究中，使用化学光热疗法（chemo-PTT）的联合疗法对肿瘤消融显示出巨大的疗效。此外,作为杂化纳米载体的脂肪聚合物,将脂质体和聚合物囊泡的优势整合在单一平台中，以提供巨大的生物相容性，生物降解性，值得注意的是，疏水性和亲水性药物的负载功效具有可调节的药物释放和高稳定性。在这项研究中,我们制造了一种多用途脂质聚合物,用于黑色素瘤的引导化疗-PTT和CT扫描成像.制备由等摩尔比的1,2-二油酰基-3-三甲基铵丙烷(DOTAP)和聚(乙二醇)-聚(乳酸)(PEG-PLA)二嵌段共聚物(摩尔比1:1)组成的脂聚合物脂质体杂化纳米囊泡。通过薄膜再水化技术制备纳米颗粒系统，用于封装多柔比星（DOX）和吲哚菁绿（ICG）以形成DOX-ICG-LP平台。在下一阶段,将AS1411DNA适体缀合至脂多聚体(Apt-DOX-ICG-LP)的表面用于选择性递送。通过DLS分析获得DOX-ICG-LP和Apt-DOX-ICG-LP的大小(分别为61.0±6和74±5)。在体外验证了所制备的脂聚合物的近红外响应释放模式。配制的平台显示出有效的光热转化，和优异的稳定性与可接受的封装效率。与体外研究一致，与单一抗癌治疗相比，NIR响应性脂聚合物对Chemo-PTT表现出明显更高的细胞毒性。此外，与接受DOX-ICG-LP或Apt-DOX-ICG-LP治疗的小鼠相比,接受Apt-DOX-ICG-LP并用808nm激光照射的B16F10荷瘤小鼠获得了具有良好生存特征的最高级肿瘤缩小。Apt-DOX-ICG-LP的诊断能力使用体内近红外成像，静脉内给药后6和24小时。结果表明Apt-DOX-ICG-LP对于黑色素瘤的诊断和双重化学-PTT的已建立的靶向治疗诊断能力的理想特征。
