Electrostatic attraction driven and shuttle-like morphology assisted enhancement for tumor uptake

Nanomaterials and nanocarriers have shown great potential in tumor theranostics, but low tumor uptake rate casts doubt on their practical applications due to competitive uptake by normal tissues and the immune system. In this work, we demonstrate the influence of electrostatic attraction and shuttle-like morphology on tumor uptake by designing positively charged Cu(II) and Fe(III) doped polyaniline (CuPani) nanoshuttles (NSs). The experimental results indicate that such nanomaterials promote cellular adhesion/internalization in vitro, and therefore enhance retention in tumor tissues. The CuPani NSs show electrostatic attraction driven nonspecific tumor recognition between oral epithelial carcinoma (KB) and Henrietta Lacks cancer (Hela) tumors. The uptake rate of CuPani NSs by negatively charged Hela tumors is up to 7.9% ID per g without any surface modification, while the uptake rate by KB tumors with a weaker charge is only 2.8% ID per g. The high tumor uptake rate is attributed to the strong electrostatic attraction of CuPani NSs with tumor tissues, which is efficient when competing against clearance by the immune system. In addition, compared with stealth effect-matched nanoparticles, the NSs show an improved tumor uptake rate due to the one-dimension-like morphology for effective cellular internalization. The synergetic enhancement of tumor uptake by electrostatic attraction and shuttle-like morphology may be helpful in the design of novel nanodevices for performing tumor theranostics.