Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Nucleolin-Targeting AS1411 Aptamer-Conjugated Nanospheres for Targeted Treatment of Glioblastoma

Kyeongjin Seo
ORCID logo ,
Kihwan Hwang
ORCID logo ,
Kyung Mi Nam
,
Min Ju Kim
ORCID logo ,
Soyeon Shin
,
Yoon-Kyu Song
* ,
Chae-Yong Kim
* ORCID logo
Version 1 : Received: 1 April 2024 / Approved: 2 April 2024 / Online: 2 April 2024 (08:52:52 CEST)

A peer-reviewed article of this Preprint also exists.

Seo, K.; Hwang, K.; Nam, K.M.; Kim, M.J.; Song, Y.-K.; Kim, C.-Y. Nucleolin-Targeting AS1411 Aptamer-Conjugated Nanospheres for Targeted Treatment of Glioblastoma. Pharmaceutics 2024, 16, 566. Seo, K.; Hwang, K.; Nam, K.M.; Kim, M.J.; Song, Y.-K.; Kim, C.-Y. Nucleolin-Targeting AS1411 Aptamer-Conjugated Nanospheres for Targeted Treatment of Glioblastoma. Pharmaceutics 2024, 16, 566.

Abstract

Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), and nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres, 100-300 nm in size, loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than nonspecific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study shows the potential for anticancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labelling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier for precisely targeting tumors. This combination has the potential to produce anti-tumor effects in active targeted therapy of GBM.

Keywords

Glioblastoma; AS1411; nucleolin; DNA nanostructures; targeted drug delivery

Subject

Medicine and Pharmacology, Medicine and Pharmacology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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