Photodynamic therapy (PDT) is a non-invasive tumor ablation modality that can be enhanced in combination with concurrent chemotherapy. Previously, we demonstrated that liposomes containing a bilayer-anchored photosensitizer (porphyrin-phospholipid; PoP) can be loaded with drugs in their aqueous core to improve drug delivery and tumor ablation upon target tissue irradiation with red-light. In the present work, we demonstrate that this concept can be extended to drugs loaded within the hydrophobic bilayer of liposomes. Cabazitaxel (CTX) is a potent second generation taxane anti-cancer drug that was loaded in the bilayer of liposomes also containing 0.1 molar% PoP, generating CTX-loaded PoP liposomes (CTX-PoP-Lip). CTX-PoP-Lip showed unilamellar vesicle morphology, and exhibited integrity in storage and serum, while maintaining drug stability under laser irradiation. In vitro cell killing evaluation showed that red-light laser irradiation induced cytotoxicity in cells incubated with CTX-PoP-Lip, compared to control treatments. In vivo pharmacokinetic analysis revealed that following intravenous administration to mice, CTX and PoP exhibited somewhat altered circulation profiles, suggesting that the CTX may have exchanged with serum factors in blood. Nevertheless, when a single treatment of CTX-PoP-Lip with laser irradiation was administered to mice bearing human MIA Paca-2 tumors, tumors were effectively ablated whereas the equivalent chemotherapy and PDT monotherapies were ineffective. These results demonstrate the versatility of liposome delivery systems for achieving tumor ablation with chemophototherapy.

Cabazitaxel is a second-generation taxane with promising anti-tumor activity and is approved for treating hormone-refractory metastatic prostate cancer previously treated with docetaxel. Although first-generation taxanes (i.e. paclitaxel and docetaxel) have sparked broad interest in a variety of drug delivery vehicles, fewer have yet been developed for cabazitaxel. This review summarizes several clinical-stage approaches for taxane formulation and recent efforts to develop novel cabazitaxel delivery systems.