Epithelial cell adhesion molecule aptamer conjugated PEG-PLGA nanopolymersomes for targeted delivery of doxorubicin to human breast adenocarcinoma cell line in vitro.

Targeted delivery of anti-cancer agents exclusively to tumor cells introduces an attractive strategy because it increases the therapeutic index compared with untargeted drugs. Aptamer conjugated nanoparticles that can specifically bind to the proteins on a tumor cell surface are capable nanoscale delivery systems for enhancing cellular uptake of chemotherapeutic agents. The epithelial cell adhesion molecule (EpCAM) as a cancer stem cell marker emerges as a versatile target for aptamer-based cancer therapy due to its high expression level in various adenocarcinoma cell lines and its very low expression level in normal cells. We developed EpCAM-targeted PEG-PLGA nanopolymersomes by covalently coupling the EpCAM aptamer to the surface of nanopolymersomes loaded with the anticancer agent doxorubicin via pH gradient method. The results indicated that doxorubicin was entrapped in PEG-PLGA nanopolymersomes with encapsulation efficiency and loading content of 91.25±4.27% and 7.3±0.34%, respectively. Over a period of 5 days, up to 8% of the DOX was released through this system. The doxorubicin-loaded aptamer conjugated nanopolymersomes exhibited efficient cell uptake and internalization, and were significantly more cytotoxic (P<0.01) toward EpCAM-positive tumor cells (MCF-7) than non-targeted nanopolymersomes. Our data suggest that EpCAM-targeted nanopolymersomes will lead to an improved therapeutic index of doxorubicin to EpCAM positive cancer cells.

Alibolandi M ，Ramezani M ，Sadeghi F ，Abnous K ，Hadizadeh F ... -  《-》

In vitro and in vivo evaluation of therapy targeting epithelial-cell adhesion-molecule aptamers for non-small cell lung cancer.

Targeted, disease-specific delivery of therapeutic nanoparticles shows wonderful promise for transmitting highly cytotoxic anti-cancer agents. Using the reaction of non-small cell lung cancer (SK-MES-1 and A549 cell lines) as representative of other cancer types', the present study examines the effects of EpCAM-fluoropyrimidine RNA aptamer-decorated, DOX-loaded, PLGA-b-PEG nanopolymersomes that bond specifically to the extracellular domain of epithelial-cell adhesion molecules. Results demonstrate that EpCAM aptamer-conjugated DOX-NPs (Apt-DOX-NP) significantly enhance cellular nanoparticle uptake in SK-MES-1 and A549 cell lines and increase the cytotoxicity of the DOX payload as compared with non-targeted DOX-NP (P<0.05). Additionally, Apt-DOX-NP exhibits greater tumor inhibition in nude mice bearing SK-MES-1 non-small cell lung-cancer xenografts and reduces toxicity, as determined by loss of body weight, cardiac histopathology and animal survival rate in vivo. After a single intravenous injection of Apt-DOX-NP and DOX-NPs, tumor volume decreased 60.9% and 31.4%, respectively, in SK-MES-1-xenograft nude mice compared with members of a saline-injected control group. This study proves the potential utility of Apt-DOX-NP for therapeutic application in non-small cell lung cancer. In the future, EpCAM-targeted therapies might play a key role in treating non-small cell lung cancer, the most common type of lung cancer.

Alibolandi M ，Ramezani M ，Abnous K ，Sadeghi F ，Atyabi F ，Asouri M ，Ahmadi AA ，Hadizadeh F ... -  《-》

EpCAM aptamer-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery.

Targeted delivery of anticancer agents by functional nanoparticles is an attractive strategy to increase their therapeutic efficacy while reducing toxicity. In this work, doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) were modified with aptamer (Ap) against the epithelial cell adhesion molecule (EpCAM) for targeted delivery of DOX to colon cancer cells. These nanoparticles (Ap-MSN-DOX) were characterized by particle size, zeta potential, aptamer conjugation efficiency, drug encapsulation efficiency, and drug release properties. The in vitro cell recognition, cellular uptake, EpCAM protein inhibition efficiency, and cytotoxicity of Ap-MSN-DOX were also studied. Results demonstrated that EpCAM conjugation increased binding of Ap-MSN-DOX to EpCAM over-expressing SW620 colon cancer cells but not EpCAM-negative Ramos cells, resulting in enhanced cellular uptake and increased cytotoxicity of the DOX in SW620 cells when compared to non-Ap-modified nanoparticles (MSN-DOX). Additionally, Ap-MSN-DOX exhibited significant inhibition effects on the expression of EpCAM on SW620 cells. These results suggested that Ap-MSN-DOX has the potential for the targeted delivery of therapeutic agents into EpCAM positive colon cancer cells to improve therapeutic index while reducing side effects.

Xie X ，Li F ，Zhang H ，Lu Y ，Lian S ，Lin H ，Gao Y ，Jia L ... -  《-》

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.

Li L ，Xiang D ，Shigdar S ，Yang W ，Li Q ，Lin J ，Liu K ，Duan W ... -  《International Journal of Nanomedicine》

The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model.

Vesicles of mPEG-PLGA block copolymer were developed to deliver a therapeutic quantity of doxorubicin (DOX) for breast cancer treatment. The DOX-loaded nanoparticles (NPs) were prepared by the pH-gradient method and then evaluated in terms of morphology, size, DOX encapsulation efficiency and in vitro drug release mechanism. The PEG-PLGA nanopolymersomes were 134±1.2nm spherical NPs with a narrow size distribution (PDI=0.121). DOX was entrapped in mPEG-PLGA nanopolymersomes with an encapsulation efficiency and a loading content of 91.25±4.27% and 7.3±0.34%, respectively. The DOX-loaded nanopolymersomes were found to be stable, demonstrating no significant change in particle size and encapsulation efficiency (EE%) during the 6-month storage period of the lyophilized powder at 4°C. The nanopolymersomes sustained the release of DOX. In cytotoxicity studies of 4T1 cell line samples, free DOX showed a higher cytotoxicity (IC50=1.76μg/mL) than did DOX-loaded nanopolymersomes (15.82μg/mL) in vitro. In order to evaluate the antitumor efficacy and biodistribution of DOX-loaded nanopolymersomes, murine breast tumors were established on the BALB/c mice, and in vivo studies were performed. The obtained results demonstrated that the prepared drug delivery system was highly effective against a murine breast cancer tumor model and successfully accumulated in the tumor site through an enhanced permeation and retention mechanism. In vivo studies also proved that DOX-loaded nanopolymersomes are stable in blood circulation and could be considered a promising and effective DOX delivery system for breast cancer treatment.

Alibolandi M ，Sadeghi F ，Abnous K ，Atyabi F ，Ramezani M ，Hadizadeh F ... -  《-》