title: A nanocapsular combinatorial sequential drug delivery system for antiangiogenesis and anticancer activities.
abstract: We reported a precise engineered nanocapsule encapsulating a neovasculature disruption agent, combretastatin A4 (CA4) in a matrix that was made up of paclitaxel (PTX) conjugated amphiphilic polyester. The nanocapsule was able to release CA4 and PTX sequentially for temporal antiangiogenesis and anticancer activities. The nanocapsule has a small particle size at 68 nm with narrow size distribution (approximately 0.15). Cellular uptake of the nanocapsule was efficient, and detectable at as early as 20 min, and drugs sequestered in the nanocapsule could exert effective therapeutic effects on tumor neovasculature and cancer cells, respectively. Biodistribution experiments demonstrated the long circulation of nanocapsule in body fluid and the preferential accumulation of nanocapsule in tumor. Both in vivo artificial pro-angiogenesis and tumor xenograft assays demonstrated the promising therapeutic effect of the nanocapsule on tumor vasculature disruption, tumor cell proliferation inhibition and tumor cell apoptosis induction. The intrasplenic liver metastasis experiment also confirmed the liver metastatic prevention capacity of this nanocapsule. In summary, the findings indicated that this dual drug loaded nanocapsule with sequential drug delivery capacity is a promising candidate in combinatorial therapy in fighting against cancer, and may open an avenue for cancer therapy and diagnosis.
authors.affiliation: Laboratory for Experimental and Applied Pharmacokinetics and Pharmacodynamics, Department of Pharmacy, National University of Singapore, 19 Science Drive, Singapore.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Paul C
authors.initials: PC
authors.lastname: Ho
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D017239:Paclitaxel / Q000737:chemistry / Q000627:therapeutic use; D013267:Stilbenes / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053769:Nanocapsules; D013267:Stilbenes; C058728:fosbretabulin; D017239:Paclitaxel