Hyaluronic Acid-Modified Nanoparticles Self-Assembled from Linoleic Acid-Conjugated Chitosan for the Codelivery of miR34a and Doxorubicin in Resistant Breast Cancer

Abstract

In this study, a chitosan-based, self-assembled nanosystem that codelivered microRNA34a (miR34a) and doxorubicin (Dox) with hyaluronic acid (HA) modification (named CCmDH NPs) was developed to reverse the resistance of breast cancer (BCa) cells to Dox. The CCmDH NPs had a diameter of 180 ± 8.3 nm and a ζ potential of 16.5 mV with a slow-release effect for 96 h. The codelivery system could protect miR34a from nuclease and serum degradation and transport miR34a and Dox into drug-resistant MCF-7/A cells. In addition, the CCmDH NPs could inhibit proliferation and promote apoptosis by regulating the protein expression of B-cell lymphoma-2 (Bcl-2) and poly­(ADP-ribose) polymerase (PARP) and inhibit invasion, metastasis, and adhesion by regulating E-cadherin, N-cadherin, MMP2, CD44, and Snail molecules. The CCmDH NPs induced a 73.7% tumor reduction in xenograft tumor growth in nude mice in vivo. This study provides evidence for the anticancer activity of CCmDH NPs carrying Dox and miR34a in BCa, especially metastatic Dox-resistant BCa models.

Peptide-Modified Cyclodextrin-Based Nanosystem for Co-Delivery of Celastrol and siPD-L1 to Tumors

“…Serum Stability of the H−C@C/siRNA NPs. According to the method proposed by Yang et al, 31 FBS was mixed with naked siRNA and nanoparticles in equal volumes and incubated at room temperature for 1, 3, 6, 12, and 24 h, respectively. The degradation of siRNA was analyzed by electrophoresis on a 3% agarose gel at 80 V for 30 min.…”

miRacle of microRNA-Driven Cancer Nanotherapeutics

“…C-A-Au NPs incorporating GFT-miR125b preferably accumulated at the tumor area in the Lewis lung carcinoma (LLC) xenograft tumor model and inhibited EGFR signaling, leading to tumor growth inhibition. A novel nanocarrier, hyaluronic acid (HA)-modified and conjugated linoleic acid (CLA)-grafted chitosan nanoparticles co-loaded with miR-34a and DOX, has been formulated [ 125 ]. Therapeutic administration of these nanosystems resulted in 73.7% tumor inhibition of MCF-7/A tumor xenografts in mice, which was higher than the other treatment arms lacking the targeting ligand, the miR-34a, or DOX.…”

Hyaluronic acid-based nano drug delivery systems for breast cancer treatment: Recent advances

“…The experimental data showed that CCmDHNPs suppressed and facilitated apoptosis by modulating protein expression of B-cell lymphoma-2 (Bcl-2) and poly (ADP-ribose) polymerase (PARP), producing sound inhibitory effects on xenograft tumors in nude mice, as well as effectively suppressed invasion, metastasis, and adhesion of breast cancer cells by regulating the levels of E-cadherin, N-cadherin, MMP2, CD44, and Snail molecules. CCmDHNPs have shown good inhibitory effects on the growth and migration of anti-DOX metastatic BCa tumors, providing an effective and novel therapeutic strategy for breast cancer treatment ( Yang et al, 2021 ).…”