Active targeting of CD4⁺ T lymphocytes by PEI-capped, peptide-functionalized gold nanoparticles

Abstract

Active targeting, which comprises recognition and attachment to target cells through receptor-ligand binding, is a promising approach for the treatment of viral infections, both as a supplement and as a potential replacement to conventional system-wide therapy. In particular, site-specific formulations for the treatment of HIV infection may overcome challenges associated with current ARV regimens. These challenges include toxicity, drug resistance and the existence of viral reservoirs. In this study we explored active targeting by synthesizing a gold nanoparticle construct decorated with an anti-CD4 cyclic peptide. The aim was to demonstrate selectivity of the system for the CD4 receptor and to deliver the RNA payload into T-lymphocytes. Colloidal gold nanoparticles functionalized with N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) were formed by a one-pot synthesis method where thiol modified polyethyleneimine (PEI) was mixed with chloroauric acid. PEI-SPDP AuNPs (gold nanoparticles) were conjugated to an anti-CD4 peptide and loaded with RNA. We measured toxicity and uptake using TZM-bl and HeLa cells. Our findings show that the nanoparticles bind selectively to CD4+ cells. No internal RNA delivery was demonstrated. Further work is required to improve internalization.

Gold Nanoparticles Contact with Cancer Cell: A Brief Update

“…Active targeting involves the functionalization of AuNP surfaces by targeting moieties, which are specific to a wide range of overexpressed surface receptors in the cancer cells, such as EGFR (epidermal growth factor receptor), human epidermal growth factor receptor-2 (HER-2) and CD44 [ 38 , 101 ] and molecules in the TME [ 102 , 103 ]. As extensively documented by many reviews [ 93 , 97 ], the functionalization of AuNPs with a plethora of targeting moieties—through electrostatic adsorption or with covalent bonds by using crosslinkers with -SH or -NH 2 groups which are able to react with the metal [ 97 , 104 , 105 ]—have been explored to support the active targeting of cancer cells and a number of very promising strategies for the selective delivery of chemotherapy drugs or molecules that must be released in the tumor cells have been developed [ 38 , 106 ]. To date, proteins [ 107 ], peptides [ 108 ], aptamer [ 109 ], lectins [ 110 ], carbohydrates [ 111 ], small molecules [ 112 ] and antibodies [ 113 ] have been exploited as targeting ligands.…”