{Reference Type}: Journal Article
{Title}: The elasticity of silicone-stabilized liposomes has no impact on their in vivo behavior.
{Author}: Hinz A;Lewandowska-Łańcucka J;Werner E;Cierniak A;Stalińska K;Dyduch G;Szuwarzyński M;Bzowska M;
{Journal}: J Nanobiotechnology
{Volume}: 22
{Issue}: 1
{Year}: 2024 Aug 5
{Factor}: 9.429
{DOI}: 10.1186/s12951-024-02698-9
{Abstract}: <B>BACKGROUND: </B>The elastomechanical properties of nanocarriers have recently been discussed as important for the efficient delivery of various therapeutics. Some data indicate that optimal nanocarriers' elasticity can modulate in vivo nanocarrier stability, interaction with phagocytes, and uptake by target cells. Here, we presented a study to extensively analyze the in vivo behavior of LIP-SS liposomes that were modified by forming the silicone network within the lipid bilayers to improve their elastomechanical properties. We verified liposome pharmacokinetic profiles and biodistribution, including retention in tumors on a mouse model of breast cancer, while biocompatibility was analyzed on healthy mice.<BR><B>RESULTS: </B>We showed that fluorescently labeled LIP-SS and control LIP-CAT liposomes had similar pharmacokinetic profiles, biodistribution, and retention in tumors, indicating that modified elasticity did not improve nanocarrier in vivo performance. Interestingly, biocompatibility studies revealed no changes in blood morphology, liver, spleen, and kidney function but indicated prolonged activation of immune response manifesting in increased concentration of proinflammatory cytokines in sera of animals exposed to all tested liposomes.<BR><B>CONCLUSIONS: </B>Incorporating the silicone layer into the liposome structure did not change nanocarriers' characteristics in vivo. Further modification of the LIP-SS surface, including decoration with hydrophilic stealth polymers, should be performed to improve their pharmacokinetics and retention in tumors significantly. Activation of the immune response by LIP-SS and LIP-CAT, resulting in elevated inflammatory cytokine production, requires detailed studies to elucidate its mechanism.