Tumor-specific liposomal drug release mediated by liposomase.
Despite the large arsenal of anticancer agents currently available and recent efforts in developing molecularly targeted therapies, the prognosis for many solid cancers remains dismal. A major obstacle to successful cancer therapy is the limited specificity of most anticancer agents. One approach to this problem is to construct drug carriers that preferentially accumulate at the cancer site, thus targeting otherwise nonselective cytotoxic chemotherapeutic agents to cancer cells. Liposomes stand out in this regard as the most successful drug carrier that has been approved for clinical use. Currently, most clinical liposomal formulations involve the use of PEGylated phospholipids that help prolong their residence time in the systemic circulation. Paradoxically, the robustness of these long-circulating formulations also obstructs the release of their payloads at the cancer site. This chapter describes a recently discovered bacterial protein capable of targeted liposome disruption within tumors.
Cheong
Ian
I
Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
Zhou
Shibin
S
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001426:Bacterial Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003013:Clostridium / Q000737:chemistry* / Q000502:physiology; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D006801:Humans; D008049:Lipase / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013171:Spores, Bacterial
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D017077:Culture Media, Conditioned; D008081:Liposomes; D008049:Lipase; C547320:liposomase, Clostridium novyi