Chemotherapy, a mainstay modality for cancer, is often hindered by systemic toxicity and side effects. With the emergence of nanomedicine, the development of drug therapy has shifted toward targeted therapy. Hyaluronan (HA) is an ideal molecule as a targeted delivery system because many carcinomas overexpress HA receptors. We have conjugated resveratrol, a natural polyphenol, and 3-(5-methoxy, 2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), a chalcone, to HA with the goal of enhancing drug bioavailability and targeting triple negative breast cancers. We demonstrate the ability of HA conjugates to accumulate in the tumor interstitium within 6 h after tail vein injections. In vitro, these conjugates interact with their target receptors, which are overexpressed by triple negative breast cancer cells under static and physiological flow. These interactions result in enhanced uptake and efficacy of the therapeutic, as demonstrated by a reduced IC₅₀ over that of nonconjugated drugs. Thus, HA offers a platform to solubilize, target, and enhance the efficacy of chemotherapeutics.

中文翻译：

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受体介导的透明质酸结合物被乳腺癌细胞吸收。

化学疗法是癌症的主要治疗手段，通常会因全身毒性和副作用而受到阻碍。随着纳米医学的出现，药物治疗的发展已转向靶向治疗。透明质酸（HA）是一种理想的分子，可作为靶向递送系统，因为许多癌过表达HA受体。我们已经缀合了白藜芦醇，天然多酚和3-（5-甲氧基，2-甲基-1 H-吲哚-3-基）-1-（4-吡啶基）-2-丙烯-1-酮（MOMIPP），查尔酮，用于HA，旨在提高药物生物利用度并靶向三阴性乳腺癌。我们证明了HA缀合物在尾静脉注射后6小时内在肿瘤间质中积累的能力。在体外，这些结合物与它们的靶受体相互作用，该靶受体在静态和生理流下被三阴性乳腺癌细胞过表达。这些相互作用导致治疗剂的吸收和功效增强，如与非结合药物相比降低的IC ₅₀所证明的。因此，HA提供了一个可增溶，靶向和增强化学治疗功效的平台。