Engineering thermosensitive liposome-nanoparticle hybrids loaded with doxorubicin for heat-triggered drug release.

The engineering of responsive multifunctional delivery systems that combine therapeutic and diagnostic (theranostic) capabilities holds great promise and interest. We describe the design of thermosensitive liposome-nanoparticle (NP) hybrids that can modulate drug release in response to external heating stimulus. These hybrid systems were successfully engineered by the incorporation of gold, silver, and iron oxide NPs into the lipid bilayer of lysolipid-containing thermosensitive liposomes (LTSL). Structural characterization of LTSL-NP hybrids using cryo-EM and AFM revealed the incorporation of metallic NPs into the lipid membranes without compromising doxorubicin loading and retention capability. The presence of metallic NPs in the lipid bilayer reinforced bilayer retention and offered a nanoparticle concentration-dependent modulation of drug release in response to external heating. In conclusion, LTSL-NP hybrids represent a promising versatile platform based on LTSL liposomes that could further utilize the properties of the embedded NPs for multifunctional theranostic applications.