The balance between the amount of drug delivered to
tumor tissue and the homogeneity of its distribution is a challenge in the efficient delivery of
photosensitizers (PSs) in
photodynamic therapy (
PDT) of
cancer. To date, many efforts have been made using various nanomaterials to efficiently deliver
temoporfin (
mTHPC), one of the most potent
photosensitizers. The present study aimed to develop double-loaded matryoshka-type hybrid nanoparticles encapsulating
mTHPC/
cyclodextrin inclusion complexes in
mTHPC-loaded
liposomes. This system was expected to improve the transport of
mTHPC to target tissues and to strengthen its accumulation in the
tumor tissue. Double-loaded hybrid nanoparticles (DL-DCL) were prepared, characterized, and tested in 2D and 3D in vitro models and in xenografted mice in vivo. Our studies indicated that DL-DCL provided deep penetration of
mTHPC into the multicellular
tumor spheroids via
cyclodextrin nanoshuttles once the
liposomes had been destabilized by
serum proteins. Unexpectedly, we observed similar
PDT efficiency in xenografted HT29
tumors for liposomal
mTHPC formulation (Foslip®) and DL-DCL.