HSA-紫杉醇和HSA-海拉酸复合物的热敏脂质体联合传递增强胰腺癌的药物灌注和功效。,ACS Applied Materials & Interfaces

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HSA-紫杉醇和HSA-海拉酸复合物的热敏脂质体联合传递增强胰腺癌的药物灌注和功效。
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2017-07-24 00:00:00 , DOI: 10.1021/acsami.7b07132
Yan Wei ₁ , Yuxi Wang _{1,

2} , Dengning Xia ₁ , Shiyan Guo ₁ , Feng Wang ₃ , Xinxin Zhang ₁ , Yong Gan ₁

Affiliation

纤维化基质和促进肿瘤的星状细胞（PSC）是胰腺导管腺癌（PDA）微环境中的关键特征，可促进促进肿瘤的环境，同时防止药物渗透到肿瘤灶中并刺激肿瘤的生长。Nab-PTX是紫杉醇（PTX）的人血清白蛋白（HSA）纳米颗粒，表明PDA中的基质渗透增强，这可能是由于其体内体积小以及HSA与分泌的酸性蛋白和富含半胱氨酸（SPARC）的蛋白具有高亲和力而导致的在PDA基质中。然而，由于其体内胶体稳定性较弱，此HSA纳米颗粒的药物血液滞留性较差，从而导致药物在肿瘤内的积累不足。将HSA纳米颗粒封装到普通脂质体的内部水相中可改善其血液滞留和随后的肿瘤聚集，但是内部的200 nm大尺寸和HSA的屏蔽可能会使这种杂化纳米药物难以穿透纤维化的PDA基质并促进有效负载的生物利用度。在我们目前的工作中，我们用抗肿瘤药（PTX）和抗PSC药物（鞣花酸，EA）制备了约9 nm的HSA复合物，并将这两种HSA-药物复合物进一步共封装在热敏脂质体（TSL）中。该纳米药物被命名为TSL / HSA-PE。使用TSL / HSA-PE可以改善药物的血液滞留，并在达到局部发热的肿瘤时，这些TSL可以快速释放其有效载荷（HSA-药物复合物），以促进其进一步的肿瘤蓄积和基质渗透。TSL / HSA-PE治疗与优异的肿瘤蓄积，令人印象深刻的基质渗透以及同时作用于肿瘤细胞和PSC破坏PSCs-PDA相互作用的作用相结合，对TSL / HSA-PE的治疗与热结合显示出强大的肿瘤生长抑制作用和凋亡体内。

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Thermosensitive Liposomal Codelivery of HSA–Paclitaxel and HSA–Ellagic Acid Complexes for Enhanced Drug Perfusion and Efficacy Against Pancreatic Cancer

Fibrotic stroma and tumor-promoting pancreatic stellate cells (PSCs), critical characters in the pancreatic ductal adenocarcinoma (PDA) microenvironment, promote a tumor-facilitating environment that simultaneously prevents drug penetration into tumor foci and stimulates tumor growth. Nab-PTX, a human serum albumin (HSA) nanoparticle of paclitaxel (PTX), indicates enhanced matrix penetration in PDA probably due to its small size in vivo and high affinity of HSA with secreted protein acidic and rich in cysteine (SPARC), overexpressed in the PDA stroma. However, this HSA nanoparticle shows poor drug blood retention because of its weak colloidal stability in vivo, thus resulting in insufficient drug accumulation within tumor. Encapsulating HSA nanoparticles into the internal aqueous phase of ordinary liposomes improves their blood retention and the following tumor accumulation, but the large 200 nm size and shielding of HSA in the interior might make it difficult for this hybrid nanomedicine to penetrate the fibrotic PDA matrix and promote bioavailability of the payload. In our current work, we prepared ∼9 nm HSA complexes with an antitumor drug (PTX) and an anti-PSC drug (ellagic acid, EA), and these two HSA–drug complexes were further coencapsulated into thermosensitive liposomes (TSLs). This nanomedicine was named TSL/HSA-PE. The use of TSL/HSA-PE could improve drug blood retention, and upon reaching locally heated tumors, these TSLs can rapidly release their payloads (HSA–drug complexes) to facilitate their further tumor accumulation and matrix penetration. With superior tumor accumulation, impressive matrix penetration, and simultaneous action upon tumor cells and PSCs to disrupt PSCs–PDA interaction, TSL/HSA-PE treatment combined with heat exhibited strong tumor growth inhibition and apoptosis in vivo.

更新日期：2017-07-25

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