Polysialic acid-functionalized liposomes for efficient honokiol delivery to inhibit breast cancer growth and metastasis

Abstract

To improve the anti-metastasis effects of honokiol (HNK) on breast cancer, we designed cationic liposomes (Lip) in which HNK was encapsulated into Lip, and its surface was modified with negatively charged polysialic acid (PSA-Lip-HNK) for efficient treatment of breast cancer. PSA-Lip-HNK possessed a homogeneous spherical shape and high encapsulation efficiency. In vitro 4T1 cell experiments indicated that PSA-Lip-HNK increased cellular uptake and cytotoxicity via the endocytosis pathway mediated by PSA and selectin receptors. Furthermore, the significant antitumor metastasis impact of PSA-Lip-HNK was confirmed by wound healing and cell migration and invasion. Enhanced in vivo tumor accumulation of the PSA-Lip-HNK was observed in 4T1 tumor-bearing mice by living fluorescence imaging. For in vivo antitumor experiments using 4T1 tumor-bearing mice, PSA-Lip-HNK exhibited a higher tumor growth and metastasis inhibition compared with unmodified liposomes. Therefore, we believe that PSA-Lip-HNK well combined biocompatible PSA nano-delivery and chemotherapy, providing a promising drug delivery approach for metastatic breast cancer therapy.

Antioxidant Nanoparticles Restore Cisplatin-Induced Male Fertility Defects by Promoting MDC1-53bp1-Associated Non-Homologous DNA Repair Mechanism and Sperm Intracellular Calcium Influx

“…However, earlier studies showed that HNK is a lipophilic polyphenol compound that exhibited poor tissue distribution and solubility when given directly; by encapsulating HNK into liposome-based nanoparticles, cellular availability, targeted tissue or cellular distribution can be optimized. [49][50][51][52] Our RNAseq analysis indicated that besides the known roles in regulating oxidative stress responses, genes related to spermatogenesis and sperm motility were also altered upon nHNK administration. We observed that upon nHNK treatment, a cell proliferation marker Ki67 and spermatogenesis marker KIF11 protein expression levels were upregulated and presented at the seminiferous tubules' outer layer where spermatogonium and primary spermatocyte locate, suggesting nHNK treatment promotes testicular cell proliferation and the subsequent restoration of spermatogenesis.…”

Furin-Catalyzed Enhanced Magnetic Resonance Imaging Probe for Differential Diagnosis of Malignant Breast Cancers

“…Cell migration and invasion abilities were found to be related to furin expression. The migration ability of the chosen cell lines (MDA-MB-231, MCF-7, and bEnd.3) can be quantified by creating a linear scratch and capturing the cells filling images at 18 h. , The migration ablility of the MDA-MB-231 group was minimal compared with that of the MCF-7 and bEnd.3 groups (Figure S4A). The wound healing rates of the MDA-MB-231, MCF-7 and bEnd.3 cell lines were 33%, 20% and 5%, respectively (Figure S4B).…”

Co-Delivery of Methotrexate and Nanohydroxyapatite with Polyethylene Glycol Polymers for Chemotherapy of Osteosarcoma

“…Moreover, nHA can more effectively extravasate into the tumor sites by the EPR effect [21]. The zeta potential (−9.1 ± 0.5 mV) provides adequate repelling force among MTX-PEG-nHA to form a stable system [38]. According to previous reports, the intracellular uptake and biodegradation of HA can lead to an increase in the concentration of calcium ions, and this further led to a decrease in the content of ATP due to mitochondrial membrane damage, thus increasing the sensitivity of chemotherapy drugs [19,20].…”