Multifunctional triblock nanocarrier (PAMAM-PEG-PLL) for the efficient intracellular siRNA delivery and gene silencing

Mahesh L. Patil, Min Zhang, Tamara Minko

Research output: Contribution to journalArticlepeer-review

188 Scopus citations


A novel triblock poly(amido amine)-poly(ethylene glycol)-poly-l-lysine (PAMAM-PEG-PLL) nanocarrier was designed, synthesized, and evaluated for the delivery of siRNA. The design of the nanocarrier is unique and provides a solution to most of the common problems associated with the delivery and therapeutic applications of siRNA. Every component in the triblock nanocarrier plays a significant role and performs multiple functions: (1) tertiary amine groups in the PAMAM dendrimer work as a proton sponge and play a vital role in the endosomal escape and cytoplasmic delivery of siRNA; (2) PEG, a linker connecting PLL and PAMAM dendrimers renders nuclease stability and protects siRNA in human plasma; (3) PLL provides primary amines to form polyplexes with siRNA through electrostatic interaction and also acts as penetration enhancer; and (4) conjugation to PEG and PAMAM reduced toxicity of PLL and the entire triblock nanocarrier PAMAM-PEG-PLL. The data obtained show that the polyplexes resulted from the conjugation of siRNA, and the proposed nanocarriers were effectively taken up by cancer cells and induced the knock down of the target BCL2 gene. In addition, triblock nanocarrier/siRNA polyplexes showed excellent stability in human plasma.

Original languageEnglish (US)
Pages (from-to)1877-1887
Number of pages11
JournalACS Nano
Issue number3
StatePublished - Mar 22 2011

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)


  • BCL2 silencing
  • PAMAM dendrimer
  • siRNA delivery
  • siRNA stability


Dive into the research topics of 'Multifunctional triblock nanocarrier (PAMAM-PEG-PLL) for the efficient intracellular siRNA delivery and gene silencing'. Together they form a unique fingerprint.

Cite this