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 language | English |
|---|---|
| Pages (from-to) | 10009-10017 |
| Number of pages | 9 |
| Journal | Journal of Physical Chemistry B |
| Volume | 125 |
| Issue number | 35 |
| DOIs | |
| State | Published - 9 Sep 2021 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2021 American Chemical Society
Funding
S.S. acknowledges the receipt of funding for his fellowship from SERB New Delhi, UGC, New Delhi, India. The authors acknowledge the support of the Central Instrument Facility of IIT (BHU), Varanasi, for the measurements. The support and resources provided by PARAM Shivay Facility under the National Supercomputing Mission, Government of India at IIT (BHU), Varanasi, are gratefully acknowledged. The authors also acknowledge the computing facility of the Department of Physics, IIT (BHU), Varanasi, developed under the DST-FIST scheme of SERB, New Delhi. The authors would like to thank Prof. S. Kumar, Department of Physics, BHU, Varanasi, for providing the computing facility.
| Funders | Funder number |
|---|---|
| University Grants Committee | |
| Science and Engineering Research Board |