MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer

Abstract

Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of HA-PEI/HA-PEG to deliver MDR1 siRNA and the efficacy of the combination of HA-PEI/HA-PEG/MDR1 siRNA with paclitaxel to suppress growth of ovarian cancer. We observed that HA-PEI/HA-PEG nanoparticles can efficiently deliver MDR1 siRNA into MDR ovarian cancer cells, resulting in down-regulation of MDR1 and Pgp expression. Administration of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles followed by paclitaxel treatment induced a significant inhibitory effect on the tumor growth, decreased Pgp expression and increased apoptosis in MDR ovarian cancer mice model. Our findings suggest that CD44 targeted HA-PEI/HA-PEG/MDR1 siRNA nanoparticles can serve as a therapeutic tool with great potentials to circumvent MDR in ovarian cancer.

Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles-polymerpolyethylenimine to improve oral squamous carcinoma treatment

“…Recently, siRNA technology has been widely used in basic research to understand the function of a specific gene and has also been used as a clinical therapeutic approach to cure a specific disease. [11][12][13][14] Doxorubicin (DOX) is a common chemotherapy medication used to treat many kinds of cancers, such as breast cancer, bladder cancer, and lymphoma. [15][16][17][18][19] DOX interacts with DNA leading to a break in the DNA strand, which blocks DNA transcription and replication, resulting in apoptosis of cancer cells.…”

Effective mRNA Inhibition in PANC-1 Cells <i>in Vitro</i> Mediated <i>via</i> an mPEG–SeSe–PEI Delivery System

“…In addition, several studies on PEGylated PEI-based nanovectors found varying results, possibly due to the differing molecular weights of PEI or PEG, 21,33) different ratios of PEG and PEI, and different methods of conjugation. 21) A further factor may be the addition of other compounds, such as bioinspired phosphorylcholine, 34) hyaluronic acid, 35) cyclic RGD, 36) and γ-polyglutamic acid. 37) Consequently, further studies on these modifications could achieve even more efficient, specific PEI-based nanovectors.…”

A Forecast of Targeting Leukemia Stem Cells by Nanomedicine

“…HA incorporated nanocarriers can deliver traditional chemotherapeutic drugs, such as doxorubicin and cyclosporine, to successfully target CD44 expressing CSCs both in vitro and in vivo [75]. This Nanomedicine based CSC targeting strategies have achieved prolonged survival in multiple animal cancer models including AML [76,[100][101][102][103]. Antibody incorporated nanocarriers have also been used for CSC targeting.…”