AS1411 aptamer tagged PEGylated liposomes as a smart nanocarrier for tumor-specific delivery of Withaferin A for mitigating pulmonary metastasis

Abstract

Metastasis is the most challenging health problem contributing to about 90 % of cancer-related deaths worldwide. Metastatic tumors are highly aggressive and resistant to the most available therapeutic options. Hence, innovative therapeutic approaches are required to target metastatic tumors selectively. In this study, we prepared AS1411 functionalized Withaferin A loaded PEGylated nanoliposomes (ALW) and investigated its therapeutic effect in B16F10 induced in pulmonary metastasis mice models. The prepared formulations' size and morphological properties were evaluated using dynamic light scattering system and Transmission electron microscope. ALW had spherical-shaped nanosized particles with a size of 118 nm and an encapsulation efficacy of 82.5 %. TEM analysis data indicated that ALW has excellent dispersibility and uniform spherical nano-size particles. ALW inhibited cell viability, and induced cell apoptosis of B16F10. In vivo, the pulmonary metastasis study in C57BL/6 mice revealed that the ALW significantly (p < 0.01) improved the encapsulated WA anti-metastatic activity and survival rate compared to WA or LW treated groups. ALW significantly (p < 0.01) downregulated the levels of IL-6, TNF-α, and IL-1β and significantly reduced the lung collagen hydroxyproline, hexosamine, and uronic acid content in metastatic tumor bearing animals compared to WA or LW. Gene expression levels of MMPs and NF-κB were downregulated in ALW treated metastatic pulmonary tumor-bearing mice. These findings demonstrate that the AS1411 functionalized Withaferin A loaded PEGylated nanoliposomes could be a promising nanoliposomal formulation for targeting metastatic tumors.