PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer.

Int J Nanomedicine

Department of Orthopedic Surgery, Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangzhou, Guangdong Province 510080, People's Republic of China.

Published: December 2020

AI Article Synopsis

  • The study focused on developing a cationic hyperbranched poly(amido amine) (HPAA) system linked with aptamers for targeted delivery of therapy against prostate cancer bone metastasis.
  • Researchers created a GSH-responsive HPAA that was modified with PEG and conjugated with an aptamer that targets prostate-specific membrane antigen (PSMA), achieving effective nanocomplex formation.
  • Experimental results showed that the HPAA-PEG-APT complexes successfully targeted PSMA-expressing cancer cells, enhanced drug delivery, reduced toxicity, and significantly inhibited tumor growth in animal models.

Article Abstract

Objective: This study aimed to develop aptamer-anchored hyperbranched poly(amido amine) (HPAA) for the systemic delivery of 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 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 into LNCaP cells was proven, and HPAA-PEG-APT/ demonstrated enhanced antitumor activity, lower cytotoxicity and better biocompatibility in vitro. Moreover, in a tibial injection tumor model, the intravenous injection of the HPAA-PEG-APT/ complex significantly inhibited cancer growth and extended the survival time.

Conclusion: This study provided an aptamer-anchored HPAA-loaded gene system to deliver for better therapeutic efficacy of bone metastasis of prostate cancer.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533908PMC
http://dx.doi.org/10.2147/IJN.S268398DOI Listing

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