Triblock Polyampholyte‐Based Nanovesicles for Targeted Spleen Delivery

Polymeric vesicles are a promising platform for targeted drug delivery. In this study, nanovesicles are developed using triblock polyampholytes composed of neutral poly(ethylene glycol), cationic poly(L-lysine), and anionic poly(α,β-aspartic acid) segments (PEG-PLys-PAsp) poly(aspartate) segments. By controlling the polymerization degree of these cationic and anionic segments, narrowly distributed nanovesicles are successfully assembled with a hydrodynamic diameter of ≈140 nm. The membrane thickness of the nanovesicles is around 15 nm, corresponding to a uniform polyion complex layer. Cross-linking the membrane of the nanovesicles via amide bonds enhance their stability in physiological salt and temperature conditions. In vivo, the cross-linked nanovesicles exhibit prolonged blood circulation and selective accumulation in the spleen after intravenous injection in mice. This approach demonstrates the potential of polyampholyte-based nanovesicles (TPBV) for targeted drug delivery applications to the spleen.