Controlled DNA Delivery Using Poly(lactide) Nanoparticles and Understanding the Binding Interactions

Sudipta Senapati, Anurag Upadhyaya, Somnath Dhruw, Debaprasad Giri, Pralay Maiti

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Cationic polymer-based gene delivery vectors suffer from several limitations such as low DNA-loading capacity, poor transfection, toxicity, environmental degradations, etc. Again, very limited works are available addressing the binding interactions in detail at the atomic level explaining the loading capacity, protection ability against harsh environments, and controlled release behavior of the DNA-encapsulated vehicles. Here, a poly(l-lactide) (PLA) nanoparticle-based controlled DNA release system is proposed. The developed vehicle possesses a high DNA-loading capacity and can release the loaded DNA in a controlled manner. Spectroscopic, physicochemical, and molecular simulation techniques (AM1 and atomistic molecular dynamics) have been employed to understand the binding interactions between PLA and DNA molecules enabling high DNA loading, protection against external harsh environments, and controlled DNA release behavior. Methyl thiazolyl tetrazolium (MTT) assay experiments confirm the biocompatible nature of the vehicle. Cellular uptake efficiency and endo-lysosomal escape capabilities have been investigated against HeLA cells. This study, therefore, demonstrates the development of a promising nonviral DNA delivery vector and includes a detailed investigation of the atomic-level interaction behavior between PLA and DNA molecules.

Original languageEnglish
Pages (from-to)10009-10017
Number of pages9
JournalJournal of Physical Chemistry B
Volume125
Issue number35
DOIs
StatePublished - 9 Sep 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society

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