Bolaamphiphiles as carriers for siRNA delivery: From chemical syntheses to practical applications

Kshitij Gupta, Kirill A. Afonin, Mathias Viard, Virginia Herrero, Wojciech Kasprzak, Ioannis Kagiampakis, Taejin Kim, Alexey Y. Koyfman, Anu Puri, Marissa Stepler, Alison Sappe, Vineet N. Kewalramani, Sarina Grinberg, Charles Linder, Eliahu Heldman, Robert Blumenthal, Bruce A. Shapiro

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Abstract In this study we have investigated a new class of cationic lipids - "bolaamphiphiles" or "bolas" - for their ability to efficiently deliver small interfering RNAs (siRNAs) to cancer cells. The bolas of this study consist of a hydrophobic chain with one or more positively charged head groups at each end. Recently, we reported that micelles of the bolas GLH-19 and GLH-20 (derived from vernonia oil) efficiently deliver siRNAs, while having relatively low toxicities in vitro and in vivo. Our previous studies validated that; bolaamphiphiles can be designed to vary the magnitude of siRNA shielding, its delivery, and its subsequent release. To further understand the structural features of bolas critical for siRNAs delivery, new structurally related bolas (GLH-58 and GLH-60) were designed and synthesized from jojoba oil. Both bolas have similar hydrophobic domains and contain either one, in GLH-58, or two, in GLH-60 positively charged head groups at each end of the hydrophobic core. We have computationally predicted and experimentally validated that GLH-58 formed more stable nano sized micelles than GLH-60 and performed significantly better in comparison to GLH-60 for siRNA delivery. GLH-58/siRNA complexes demonstrated better efficiency in silencing the expression of the GFP gene in human breast cancer cells at concentrations of 5 μg/mL, well below the toxic dose. Moreover, delivery of multiple different siRNAs targeting the HIV genome demonstrated further inhibition of virus production.

Original languageEnglish
Article number7746
Pages (from-to)142-151
Number of pages10
JournalJournal of Controlled Release
StatePublished - 18 Jul 2015


  • Bolaamphiphiles
  • Cryo-EM
  • FRET
  • Molecular dynamics simulations
  • RNAi induced gene silencing
  • siRNA drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science


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