Direct and Noninvasive Penetration of Bare Hydrophobic Quantum Dots through Live Cell Membranes

Semiconductor quantum dots (QDs) possess outstanding optical properties as fluorescent probes, but their applications in live cell intracellular imaging are hindered by various cellular transport barriers. Inspired by membrane proteins inserting their nanometer-scale hydrophobic surface into biomembranes, the present work aims to investigate the possibility that bare hydrophobic QDs could penetrate through live cell membranes without disrupting the membrane integrity. We utilize live cell spinning disk confocal microscopy to image and track the cellular transport process of bare hydrophobic QDs in the presence of a small percentage of three different organic cosolvents, namely, tetrahydrofuran (THF), chloroform, and hexane. A major finding is that, under certain cosolvent conditions, bare hydrophobic QDs can indeed penetrate through biomembranes in a noninvasive manner. Results of this work offer us guidance to design a new class of nanobioprobes based on combining hydrophobic nanoscale surface and cosolvent, and they provide key new pieces to the emerging complex and sophisticated picture of nanostructure-biosystem interactions.