Objective: This study aimed to develop aptamer-anchored hyperbranched poly(amido amine) (HPAA) for the systemic delivery of miRNA-133a-3p  and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro.
Methods: A glutathione (GSH)-responsive cationic HPAA was prepared by the Michael addition reaction. Furthermore, HPAA-PEG was produced by PEGylation, and then the aptamer targeted to prostate-specific membrane antigen (PSMA) was conjugated to the HPAA-PEG. The obtained HPAA-PEG-APT could form nanocomplexes with miRNA-133a-3p  through electrostatic adsorption.
Results: The results of immunocytochemistry indicated that the complexes could target PSMA-expressing LNCaP cells. The ability of HPAA-PEG-APT to facilitate the delivery of miRNA-133a-3p  into LNCaP cells was proven, and HPAA-PEG-APT/miRNA-133a-3p  demonstrated enhanced antitumor activity, lower cytotoxicity and better biocompatibility in vitro. Moreover, in a mouse  tibial injection tumor model, the intravenous injection of the HPAA-PEG-APT/miRNA-133a-3p  complex significantly inhibited cancer growth and extended the survival time.
Conclusion: This study provided an aptamer-anchored HPAA-loaded gene system to deliver miRNA-133a-3p  for better therapeutic efficacy of bone metastasis of prostate cancer.
Keywords: miRNA, aptamer, hyperbranched polyamide amine, bone metastasis, prostate cancer