{Reference Type}: Journal Article
{Title}: A Poly(amino acid)-Based Nanomedicine Strategy: Telomere-Telomerase Axis Targeting and Magnetic Resonance Imaging in Hepatocellular Carcinoma Treatment.
{Author}: Zhang J;Yang XY;Chen J;Zhou Q;Pan G;Wang Y;Luo W;Hou J;Bao H;Xu G;Tang G;Bai H;Yu R;
{Journal}: Nano Lett
{Volume}: 24
{Issue}: 27
{Year}: 2024 Jul 10
{Factor}: 12.262
{DOI}: 10.1021/acs.nanolett.4c01767
{Abstract}: Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone. By leveraging D-PAAs' modifiability, we synthesize polymer-inhibitor conjugates (PB and PI) and a folic acid-decorated tumor-targeting vector (PF). These building blocks undergo micellization to fabricate a codelivery nanomedicine (P-BI@P-FA) by exploiting D-PAAs' noncovalent assembly. P-BI@P-FA improves the pharmacokinetics, tumor selectivity, and bioavailability of small molecule inhibitors and initiates a dual telomere-specific inhibition by combining telomerase deactivation with telomere disruption. Furthermore, a hybrid tumor-targeting magnetic nanosystem is designed using D-PAAs and manganese dioxide to showcase magnetic resonance imaging capacities. Our D-PAAs-based strategy addresses the pressing need for telomere-specific HCC treatment while allowing for diagnostic application, presenting a promising avenue for nanomedicine design.