Huang Jianxi, Chien Yu-Ting, Mu Qingxin, Zhang Miqin
Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.
Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA.
Pharmaceutics. 2024 Sep 25;16(10):1246. doi: 10.3390/pharmaceutics16101246.
Cancer remains one of the leading causes of death, with breast, liver, and pancreatic cancers significantly contributing to this burden. Traditional treatments face issues including dose-limiting toxicity, drug resistance, and limited efficacy. Combining therapeutic agents can enhance effectiveness and reduce toxicity, but separate administration often leads to inefficiencies due to differing pharmacokinetics and biodistribution. Co-formulating hydrophobic chemotherapeutics such as paclitaxel (PTX) and hydrophilic immunologic agents such as polyinosinic-polycytidylic acid (Poly IC) is particularly challenging due to their distinct physicochemical properties. This study presents a novel and efficient approach for the co-delivery of PTX and Poly IC using chitosan-based nanoparticles. Chitosan-PEG (CP) nanoparticles were developed to encapsulate both PTX and Poly IC, overcoming their differing physicochemical properties and enhancing therapeutic efficacy. : With an average size of ~100 nm, these nanoparticles facilitate efficient cellular uptake and stability. In vitro results showed that CP-PTX-Poly IC nanoparticles significantly reduced cancer cell viability in breast (4T1), liver (HepG2), and pancreatic (Pan02) cancer types, while also enhancing dendritic cell (DC) maturation. : This dual-modal delivery system effectively combines chemotherapy and immunotherapy, offering a promising solution for more effective cancer treatment and improved outcomes.
癌症仍然是主要死因之一，乳腺癌、肝癌和胰腺癌在很大程度上加重了这一负担。传统治疗方法面临着诸如剂量限制性毒性、耐药性和疗效有限等问题。联合使用治疗药物可以提高疗效并降低毒性，但由于药代动力学和生物分布不同，分开给药往往效率低下。由于疏水性化疗药物如紫杉醇（PTX）和亲水性免疫制剂如聚肌苷酸-聚胞苷酸（Poly IC）具有不同的物理化学性质，将它们共同配制尤其具有挑战性。本研究提出了一种使用基于壳聚糖的纳米颗粒共递送PTX和Poly IC的新颖且有效的方法。开发了壳聚糖-聚乙二醇（CP）纳米颗粒来包裹PTX和Poly IC，克服它们不同的物理化学性质并提高治疗效果。这些纳米颗粒平均尺寸约为100纳米，有助于高效的细胞摄取和稳定性。体外结果表明，CP-PTX-Poly IC纳米颗粒显著降低了乳腺癌（4T1）、肝癌（HepG2）和胰腺癌（Pan02）细胞的活力，同时还促进了树突状细胞（DC）的成熟。这种双模式递送系统有效地结合了化疗和免疫疗法，为更有效的癌症治疗和改善治疗结果提供了一个有前景的解决方案。
