Synergistic Antitumor Effects of Doxorubicin-Loaded Carboxymethyl Cellulose Nanoparticle in Combination with Endostar for Effective Treatment of Non-Small-Cell Lung Cancer

• Published in: Advanced healthcare materials Vol. 3; no. 11; pp. 1877 - 1888
• Main Authors: Li, Mingqiang, Tang, Zhaohui, Lin, Jian, Zhang, Yu, Lv, Shixian, Song, Wantong, Huang, Yubin, Chen, Xuesi
• Format: Journal Article
• Language: English
• Published: Weinheim Blackwell Publishing Ltd 01-11-2014; Wiley-VCH; Wiley Subscription Services, Inc
• Subjects: Angiogenesis Inhibitors - administration & dosage; antiangiogenic therapy; Antiangiogenics; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Biological and medical sciences; Cancer; Cancer therapies; Carboxymethylcellulose Sodium - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Cell Line, Tumor; Cellulose; Chemotherapy; combination therapy; Cross-disciplinary physics: materials science; rheology; doxorubicin; Doxorubicin - administration & dosage; Drug Carriers - administration & dosage; Drug Delivery Systems - methods; Drug Stability; Drug Synergism; Drugs; Effectiveness; endostar; Exact sciences and technology; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lungs; Materials science; Medical sciences; Nanoparticles - administration & dosage; Nanoscale materials and structures: fabrication and characterization; Nanostructure; non-small-cell lung cancer; Pharmaceutical industry; Pharmacology. Drug treatments; Physics; Therapy; Tissue Distribution; Antineoplastic agent; Nanoparticle; Toxicity; Lung cancer; Endostatin; non-small cell lung carcinoma; Doxorubicin; Isomerases; Efficiency; Bronchus disease; Antiangiogenic agent; Nanomedicine; Cellulose ether; DNA topoisomerase (ATP-hydrolysing); Lung disease; Drug combination; Cellulose(carboxymethyl); Enzyme; Respiratory disease; Rodentia; Enzyme inhibitor; Topoisomerase II inhibitor; Malignant tumor; Polyelectrolyte; Vertebrata; Antibiotic; Mammalia; Treatment; Mouse; Animal; Cellulose derivatives; Anthracyclins; Polyacid; Pharmacokinetics; Cancer; combination therapy; antiangiogenic therapy; doxorubicin; endostar; non-small-cell lung cancer
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201400108

The multi‐modal combination therapy is proved powerful and successful to enhance the antitumor efficacy in clinics as compared with single therapy modes. In this study, the potential of combining chemotherapy with antiangiogenic therapy for the treatment of non‐small‐cell lung cancer is explored. Towards this aim, OEGylated carboxymethyl cellulose–(2‐(2‐(2‐methoxyethoxy)ethoxy)methyl)oxirane (CMC–ME2MO) is prepared by treating CMC with ME2MO in the alkaline aqueous solution, and used to efficiently carry doxorubicin (DOX) with high drug‐loading content (16.64%) and encapsulation efficiency (99.78%). As compared to free DOX, the resulting nanoparticles show not only the favorable stability in vitro but also the prolonged blood circulation, improved safety and tolerability, optimized biodistribution, reduced systemic toxicity, and enhanced antitumor efficacy in vivo, indicates a potential utility in cancer chemotherapy. Furthermore, the combination of the DOX‐loaded polysaccharide nanoparticles and antiangiogenic drug endostar provides synergistic effects of chemotherapy and antiangiogenic therapy, which shows the highest efficiency in tumor suppression. The combination approach of the DOX‐containing nanomedicine and endostar for efficient treatment of non‐small‐cell lung cancer is first proposed to demonstrate the synergistic therapeutic effect. This synergistic combination proves to be a promising therapeutic regimen in cancer therapy and holds great potential for clinical application.
Both angiogenesis and cancer cell proliferation are the main features of tumor tissues. Combinational chemotherapy and antiangiogenic therapy strategy, based on the doxorubicin‐containing nanomedicine and antiangiogenic drug endostar, demonstrate remarkably synergistic antitumor and antiangiogenesis effects for the treatment of non‐small‐cell lung cancer. This synergistic combination provides a convenient, safe, and efficient approach for cancer treatment.