Doxorubicin (DOX) is a potent anti-cancer agent that has garnered great interest in
research due to its high efficacy despite dose-limiting toxicities. Several strategies
have been exploited to enhance the efficacy and safety profile of DOX. Liposomes are
the most established approach. Despite the improvement in safety properties of liposomal
encapsulated DOX (in Doxil and Myocet), the efficacy is not superior to conventional
DOX. Functionalized (targeted) liposomes present a more effective system to deliver
DOX to the tumor. Moreover, encapsulation of DOX in pH-sensitive liposomes (PSLs)
or thermo-sensitive liposomes (TSLs) combined with local heating has improved DOX
accumulation in the tumor. Lyso-thermosensitive liposomal DOX (LTLD), MM-302, and
C225-immunoliposomal(IL)-DOX have reached clinical trials. Further functionalized
PEGylated liposomal DOX (PLD), TSLs, and PSLs have been developed and evaluated in
preclinical models. Most of these formulations improved the anti-tumor activity compared
to the currently available liposomal DOX. However, the fast clearance, the optimization
of ligand density, stability, and release rate need more investigations. Therefore,
we reviewed the latest approaches applied to deliver DOX more efficiently to the tumor,
preserving the benefits obtained from FDA-approved liposomes.
