Cetuximab-Coated Thermo-Sensitive Liposomes Loaded with Magnetic Nanoparticles and Doxorubicin for Targeted EGFR-Expressing Breast Cancer Combined Therapy.

One major limitation of cancer chemotherapy is a failure to specifically target a tumor, potentially leading to side effects such as systemic cytotoxicity. In this case, we have generated a cancer cell-targeting nanoparticle-liposome drug delivery system that can be activated by near-infrared laser light to enable local photo-thermal therapy and the release of chemotherapeutic agents, which could achieve combined therapeutic efficiency. To exploit the magnetic potential of iron oxide, we prepared and characterized citric acid-coated iron oxide magnetic nanoparticles (CMNPs) and encapsulated them into thermo-sensitive liposomes (TSLs). The chemotherapeutic drug, doxorubicin (DOX), was then loaded into the CMNP-TSLs, which were coated with an antibody against the epidermal growth factor receptor (EGFR), cetuximab (CET), to target EGFR-expressing breast cancer cells in vitro and in vivo studies in mouse model. The resulting CET-DOX-CMNP-TSLs were stable with an average diameter of approximately 120 nm. First, the uptake of TSLs into breast cancer cells increased by the addition of the CET coating. Next, the viability of breast cancer cells treated with CET-CMNP-TSLs and CET-DOX-CMNP-TSLs was reduced by the addition of photo-thermal therapy using near-infrared (NIR) laser irradiation. What is more, the viability of breast cancer cells treated with CMNP-TSLs plus NIR was reduced by the addition of DOX to the CMNP-TSLs. Finally, photo-thermal therapy studies on tumor-bearing mice subjected to NIR laser irradiation showed that treatment with CMNP-TSLs or CET-CMNP-TSLs led to an increase in tumor surface temperature to 44.7°C and 48.7°C, respectively, compared with saline-treated mice body temperature ie, 35.2°C. Further, the hemolysis study shows that these nanocarriers are safe for systemic delivery. Our studies revealed that a combined therapy of photo-thermal therapy and targeted chemotherapy in thermo-sensitive nano-carriers represents a promising therapeutic strategy against breast cancer.

Dorjsuren B ，Chaurasiya B ，Ye Z ，Liu Y ，Li W ，Wang C ，Shi D ，Evans CE ，Webster TJ ，Shen Y ... -  《International Journal of Nanomedicine》

EGFR-Targeted and NIR-Triggered Lipid-Polymer Hybrid Nanoparticles for Chemo-Photothermal Colorectal Tumor Therapy.

Fang F ，Chen YY ，Zhang XM ，Tang J ，Liu YH ，Peng CS ，Sun Y ... -  《International Journal of Nanomedicine》

The comparative effect of wrapping solid gold nanoparticles and hollow gold nanoparticles with doxorubicin-loaded thermosensitive liposomes for cancer thermo-chemotherapy.

Li Y ，He D ，Tu J ，Wang R ，Zu C ，Chen Y ，Yang W ，Shi D ，Webster TJ ，Shen Y ... -  《-》

Magnetic Graphene Oxide for Dual Targeted Delivery of Doxorubicin and Photothermal Therapy.

Lu YJ ，Lin PY ，Huang PH ，Kuo CY ，Shalumon KT ，Chen MY ，Chen JP ... -  《Nanomaterials》

EGFR-targeted hybrid lipid nanoparticles for chemo-photothermal therapy against colorectal cancer cells.

Antibody-functionalized targeted nanocarriers have shown great-potential for minimizing the chemoresistance and systemic toxicity of cancer chemotherapies. The combination of chemotherapy and photothermal therapy has great potential in improving therapeutic effect. However, cetuximab-modified nanoparticles based lipids for chemo-phototherapy of EGFR overexpressing colorectal carcinoma (CRC) have seldom been investigated. Hence, this study aimed to fabricate cetuximab-conjugated and near infrared (NIR) light-responsive hybrid lipid-polymer nanoparticles (abbreviated as Cet-CINPs) for targeted delivery of irinotecan. Cet-CINPs were prepared with copolymer PLGA and various lipids DSPE-PEG, DSPE-PEG-Mal, lecithin as carriers. Cetuximab was conjugated on the surface of nanoparticles to achieve targeting anti-tumor efficacy. Cet-CINPs were characterized in terms of morphology (spherical), size (119 nm), charge (-27.2 mV), drug entrapment efficiency (43.27 %), and antibody conjugation efficiency (70.87 %). Cet-CINPs showed preferable photothermal response, pH/NIR-triggered drug release behavior, enhanced cellular uptake and ROS level compared with free ICG and CINPs. Meanwhile, in vitro cytotoxicity assay showed that Cet-CINPs with NIR irradiation had a higher cytotoxicity against Lovo cells than non-targeted or non-NIR activated nanoparticles. The IC50 values of Cet-CINPs with NIR irradiation was 22.84 ± 1.11 μM for 24 h and 5.01 ± 1.06 μM for 48 h, respectively. These investigations demonstrate that Cet-CINPs with good tumor-targeting ability and enhanced antitumor activity, are a promising multifunctional nanoplatform for CRC therapy.

Fang F ，Zhang X ，Tang J ，Wang Y ，Xu J ，Sun Y ... -  《-》