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  • Title: HPA aptamer functionalized paclitaxel-loaded PLGA nanoparticles for enhanced anticancer therapy through targeted effects and microenvironment modulation.
    Author: Duan T, Xu Z, Sun F, Wang Y, Zhang J, Luo C, Wang M.
    Journal: Biomed Pharmacother; 2019 Sep; 117():109121. PubMed ID: 31252265.
    Abstract:
    Breast cancer is a fairly common cancer with high mortality in women worldwide. Targeted nano-drug delivery system for breast cancer treatment has achieved encouraging results, because of increased drug concentration at the tumor site, thereby improving biocompatibility and blood half-life while reducing chemoresistance. However, the absence of available target on cancer cells is one of the major obstacles for triple-negative breast cancer (TNBC). Increasing studies have shown that heparanase (HPA) is highly expressed in many cancers, including TNBC. Thus paclitaxel(PTX) -encapsulated PEGylated PLGA nanoparticles were developed and further surface-functionalized with the HPA aptamers (Apt(S1.5)-PTX-NP). Moreover, targeting and cytotoxicity of Apt(S1.5)-PTX-NP to TNBC cells were evaluated with MDA-MB-231 as a model. These nanoparticles bonded to the HPA overexpressed on the surface of TNBC cells and were taken up by these cells, resulting in remarkably enhanced cellular toxicity compared with non-targeted PTX-NP that lack the HPA aptamer (P < 0.01). Furthermore, Apt(S1.5)-PTX-NP significantly exhibited enhanced anti-invasive and superior anti-angiogenesis activity compared with those of other experiment groups at low administration dosage. The Apt(S1.5)-PTX-NP demonstrated the most dramatic efficacy with the final mean tumor sizes of 157.30 ± 41.09 mm3 (mean ± SD; n = 10) in vivo treatment. Thus, the present study indicated that HPA is a promising target for drug delivery to TNBC cells, and nanoparticle-HPA-aptamer bioconjugates can provide new insights for TNBC treatment.
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