关键词: cancer-associated fibroblasts combination therapy drug delivery glucocorticoids

Mesh : Tumor Microenvironment / drug effects Animals Female Breast Neoplasms / drug therapy pathology Humans Mice Liposomes / chemistry MCF-7 Cells Doxorubicin / pharmacology chemistry administration & dosage pharmacokinetics Cell Proliferation / drug effects Mice, Inbred BALB C NIH 3T3 Cells Chondroitin Sulfates / chemistry pharmacology Particle Size Nanoparticle Drug Delivery System / chemistry Drug Delivery Systems / methods Cell Movement / drug effects Nanoparticles / chemistry

来  源:   DOI:10.2147/IJN.S460874   PDF(Pubmed)

Abstract:
UNASSIGNED: Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells.
UNASSIGNED: Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro \"condition medium of fibroblasts + MCF-7\" cell model and in vivo \"4T1/NIH-3T3\" co-implantation mice model were established to evaluate the anti-tumor effect of drugs.
UNASSIGNED: The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect.
UNASSIGNED: In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.
摘要:
乳腺癌是全世界女性中普遍存在的恶性肿瘤,恶性肿瘤与肿瘤微环境(TME)密切相关。这里,我们制备了由pH敏感脂质体(Ber/Ru486@CLPs)和小尺寸纳米胶束(Dox@CLGs)组成的混合纳米制剂。通过硫酸软骨素(CS)修饰这些脂质体和纳米胶束以选择性靶向乳腺癌细胞。
Ber/Ru486@CLPs和Dox@CLGs通过薄膜分散和乙醇注射制备,分别。为了模仿实际的TME,建立体外“成纤维细胞条件培养基+MCF-7”细胞模型和体内“4T1/NIH-3T3”共植入小鼠模型,以评估药物的抗肿瘤作用。
理化性质表明,Dox@CLGs和Ber/Ru486@CLPs的粒径分别为28nm和100nm,分别。体外实验表明,混合制剂显著提高了药物摄取,抑制了细胞增殖和迁移。体内抗肿瘤研究进一步证实了Dox@CLGs+Ber/Ru486@CLPs的抗肿瘤能力增强,包括较小的肿瘤体积,弱胶原蛋白沉积,和低表达水平的α-SMA和CD31蛋白,导致优越的抗肿瘤效果。
简而言之,这种基于Dox@CLGs和Ber/Ru486@CLPs的联合治疗可以有效抑制肿瘤的发展,这为乳腺癌的治疗提供了一种有希望的方法。
公众号