Improvement in the drug delivery and anti-tumor efficacy of PEGylated liposomal doxorubicin by targeting RNA aptamers in mice bearing breast tumor model

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 139; pp. 228 - 236
• Main Authors: Moosavian, Seyedeh Alia, Abnous, Khalil, Badiee, Ali, Jaafari, Mahmoud Reza
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2016
• Subjects: Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacokinetics; Antibiotics, Antineoplastic - pharmacology; Aptamer; Aptamers, Nucleotide - chemistry; Bearing; Breast; Breast cancer; Cancer targeting; Cattle; Cell Line, Tumor; Doxorubicin; Doxorubicin - analogs & derivatives; Doxorubicin - chemistry; Doxorubicin - pharmacokinetics; Doxorubicin - pharmacology; Drug Compounding; Drug Delivery Systems - methods; Drug Liberation; Drug Screening Assays, Antitumor; Effectiveness; Female; Liposomes; Liposomes - chemistry; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - metabolism; Mammary Glands, Animal - pathology; Mammary Neoplasms, Animal - drug therapy; Mammary Neoplasms, Animal - metabolism; Mammary Neoplasms, Animal - pathology; Mice; Mice, Inbred BALB C; Molecular Targeted Therapy; PEGylated-liposomal doxorubicin; Phosphatidylcholines - chemistry; Phosphatidylethanolamines - chemistry; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacokinetics; Polyethylene Glycols - pharmacology; Ribonucleic acids; Static Electricity; Tumors; PEGylated-liposomal doxorubicin; Aptamer; Breast cancer; Cancer targeting
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2015.12.009

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•Recently developed RNA aptamer was conjugated to PEGylated liposomal doxorubicin.•Aptamers improved cellular uptake and cell cytotoxicity of liposomes.•Targeted liposomes had higher tumor accumulation and higher anti-tumor efficiency compared with non-targeted liposomes in BALB/c mice.
Targeted delivery by ligands such as aptamers, is a promising method to increase the efficiency of PEGylated-liposomal doxorubicin (PL-Dox). In this study, we have successfully conjugated our recently developed anti-breast cancer RNA aptamer (TSA14) to the surface of PL-Dox and characterized for their size, zeta potential, Dox percent encapsulation and release properties in the presence of fetal bovine serum. In vitro experiments showed that aptamer could improve cellular uptake and cytotoxicity of PL-Dox in TUBO breast cell line. In mice bearing TUBO breast tumor, although, the doxorubicin plasma level of liposomal doxorubicin did not significantly change after modification of nanoparticles with aptamer, however, much higher tumor accumulation of Dox as compared with non-targeted liposomes proved the tumor-targeting capability of aptamers. In the same way, aptamer-PL-Dox improved anti-tumor efficiency of liposomes in TUBO breast tumor in mice compared to non-targeted liposomes. Overall, the results showed that aptamer decoration of PL-Dox could significantly improve selectivity and the therapeutic efficacy of liposomal DOX and merits further investigation.