PAMAM-Calix-Dendrimers: Third Generation Synthesis and Impact of Generation and Macrocyclic Core Conformation on Hemotoxicity and Calf Thymus DNA Binding
Olga Mostovaya,
Igor Shiabiev,
Daniil Ovchinnikov,
Dmitry Pysin,
Timur Mukhametzyanov,
Alesia Stanavaya,
Viktar Abashkin,
Dzmitry Shcharbin,
Arthur Khannanov,
Marianna Kutyreva,
Mingwu Shen,
Xiangyang Shi,
Pavel Padnya,
Ivan Stoikov
Affiliations
Olga Mostovaya
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia
Igor Shiabiev
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia
Daniil Ovchinnikov
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia
Dmitry Pysin
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia
Timur Mukhametzyanov
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia
Alesia Stanavaya
Institute of Biophysics and Cell Engineering of NASB, 27 Akademicheskaya St., 220072 Minsk, Belarus
Viktar Abashkin
Institute of Biophysics and Cell Engineering of NASB, 27 Akademicheskaya St., 220072 Minsk, Belarus
Dzmitry Shcharbin
Institute of Biophysics and Cell Engineering of NASB, 27 Akademicheskaya St., 220072 Minsk, Belarus
Arthur Khannanov
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia
Marianna Kutyreva
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia
Mingwu Shen
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China
Xiangyang Shi
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China
Pavel Padnya
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia
Ivan Stoikov
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia
Background/Objectives: Current promising treatments for many diseases are based on the use of therapeutic nucleic acids, including DNA. However, the list of nanocarriers is limited due to their low biocompatibility, high cost, and toxicity. The design of synthetic building blocks for creating universal delivery systems for genetic material is an unsolved problem. In this work, we propose PAMAM dendrimers with rigid thiacalixarene core in various conformations, i.e., PAMAM-calix-dendrimers, as a platform for a supramolecular universal constructor for nanomedicine. Results: Third generation PAMAM dendrimers with a macrocyclic core in three conformations (cone, partial cone, and 1,3-alternate) were synthesized for the first time. The obtained dendrimers were capable of binding and compacting calf thymus DNA, whereby the binding efficiency improved with increasing generation, while the influence of the macrocyclic core was reduced. A dramatic effect of the macrocyclic core conformation on the hemolytic activity of PAMAM-calix-dendrimers was observed. Specifically, a notable reduction in hemotoxicity was associated with a decrease in compound amphiphilicity. Conclusions: We hope the results will help reduce financial and labor costs in developing new drug delivery systems based on dendrimers.
