alexa Antineovascular therapy with angiogenic vessel-targeted polyethyleneglycol-shielded liposomal DPP-CNDAC.
Microbiology

Microbiology

Journal of Antivirals & Antiretrovirals

Author(s): Asai T, Miyazawa S, Maeda N, Hatanaka K, Katanasaka Y,

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Abstract Causing damage to angiogenic vessels is a promising approach for cancer chemotherapy. The present study is a codification of a designed liposomal drug delivery system (DDS) for antineovascular therapy (ANET) with 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (CNDAC). The authors have previously reported that liposomalized 5'-O-dipalmitoylphosphatidyl CNDAC (DPP-CNDAC), a phospholipid derivative of the novel antitumor nucleoside CNDAC, is quite useful for ANET. DPP-CNDAC liposomes modified with APRPG, a peptide having affinity toward angiogenic vessels, efficiently suppressed tumor growth by damaging angiogenic endothelial cells. In the present study, the authors masked the hydrophilic moiety of DPP-CNDAC, namely, CNDAC, on the liposomal surface with APRPG-polyethyleneglycol (PEG) conjugate to improve the availability of DPP-CNDAC liposomes. The use of the APRPG-PEG conjugate attenuated the negative zeta-potential of the DPP-CNDAC liposomes and reduced the agglutinability of them in the presence of serum. These effects improved the blood level of DPP-CNDAC liposomes in colon 26 NL-17 tumor-bearing BALB/c male mice, resulting in enhanced accumulation of them in the tumor. Laser scanning microscopic observations indicated that APRPG-PEG-modified DPP-CNDAC liposomes (LipCNDAC/APRPG-PEG) colocalized with angiogenic vessels and strongly induced apoptosis of tumor cells, whereas PEG-modified DPP-CNDAC liposomes (LipCNDAC/PEG) did not. In fact, LipCNDAC/APRPG-PEG suppressed the tumor growth more strongly compared to LipCNDAC/PEG and increased significantly the life span of the mice. The present study is a good example of an effective liposomal DDS for ANET that is characterized by: (i) phospholipid derivatization of a certain anticancer drug to suit the liposomal formulation; (ii) PEG-shielding for masking undesirable properties of the drug on the liposomal surface; and (iii) active targeting to angiogenic endothelial cells using a specific probe. This article was published in Cancer Sci and referenced in Journal of Antivirals & Antiretrovirals

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