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一种用于多癌响应性化学免疫共递送纳米颗粒的高效制备方法。

An Efficient Fabrication Approach for Multi-Cancer Responsive Chemoimmuno Co-Delivery Nanoparticles.

作者信息

Huang Jianxi, Chien Yu-Ting, Mu Qingxin, Zhang Miqin

机构信息

Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.

Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA.

出版信息

Pharmaceutics. 2024 Sep 25;16(10):1246. doi: 10.3390/pharmaceutics16101246.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/674b/11510515/5801af6f19cc/pharmaceutics-16-01246-g001.jpg

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