Sulfonate modified Lactoferrin nanoparticles as drug carriers with dual activity against HIV-1

[Display omitted] •Studies previously reported the use of Lactoferrin Nanoparticles for delivery of anti-HIV drugs.•The free Cysteines on Lactoferrin facilitated the conjugation of Sulfonate groups on the surface of nanoparticles.•The sulfonate groups mimic the negative charges of Tyrosine sulfates of CCR5 and Heparan sulfate.•Their interaction with V3 loop inhibits viral entry and delivers anti-HIV drugs, thus making them dual active. Intriguing properties and structural dynamics of Lactoferrin have been exploited in numerous applications, including its use as self-assembling, pH sensitive nanoparticles to deliver intended cargo at the disease site. In this study, we explore the possibility of surface modification of Lactoferrin nanoparticles to hone its specificity to target HIV-1 infected cells. Existence of free cysteine groups on Lactoferrin nanoparticles available for reaction with external molecules facilitates conjugation on the surface with Sodium 2-mercaptoethanesulfonate (MES). Conjugation with MES is used to edge a negative charge that can mimic CCR5 and Heparan sulfate (initial point of contact of HIV-1 env to host cell surface) electrostatic charge (Sulfate group). A simple sono-chemical irradiation method was employed for self-assembly of Nanoparticles and for surface modification. The nanoparticles serve dual purpose to abrogate extracellular entry and to target viral enzymes, when loaded with ART drugs. The morphology and size distribution of the formed particles were explored using Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM) and Dynamic Light Scattering. Raman SERS was employed to understand the difference in the protein upon surface modification. The anti-HIV property of the particles was confirmed in-vitro. The modified device demonstrated acceptable nanoparticle properties with controlled release and higher effective concentration in the area of infection.