title: Combretastatin-A4 phosphate improves the distribution and antitumor efficacy of albumin-bound paclitaxel in W256 breast carcinoma model.
abstract: Nanomedicine holds great promise for fighting against malignant tumors. However, tumor elevated interstitial fluid pressure (IFP) seriously hinders convective transvascular and interstitial transport of nanomedicines and thus damages its antitumor efficacy. In this study, combretastatin-A4 phosphate (CA4P) was utilized to reduce tumor IFP, and thereby to improve the intratumoral distribution and antitumor efficacy of nanoparticle albumin-bound paclitaxel (nab-paclitaxel). IFP was measured using the wick-in-needle method in tumors growing subcutaneously pretreatment and posttreatment with a single intravenous injection of CA4P. The tracing method of iodine 131 isotope was used for biodistribution analysis of nab-paclitaxel. Liquid chromatography coupled with tandem mass spectrometry was used to detect the intratumoral concentration of paclitaxel. Magnetic resonance imaging was applied to monitor tumor volume and ratios of necrosis. The tumor IFP continued to decline gradually over time following CA4P treatment, reaching approximately 31% of the pretreatment value by 1 h posttreatment. Biodistribution data indicated that both 131I-nab-paclitaxel and paclitaxel exhibited higher tumor uptake in CA4P + 131I-nab-paclitaxel group compared with I131-nab-paclitaxel group. Nab-paclitaxel combined with CA4Pshowed significant tumor growth inhibition and higher tumor necrosis ratio relative to PBS, CA4P and nab-paclitaxel group, respectively. In conclusion, CA4P improved the intratumoral distribution and antitumor efficacy of nab-paclitaxel in W256 tumor-bearing rats.
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors.forename: Dongjian
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors.forename: Qiaomei
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Natural Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, P.R. China.
authors.forename: Jindian
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors.forename: Fei
authors.initials: F
authors.lastname: Peng
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors.forename: Dejian
authors.initials: D
authors.lastname: Huang
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Song
mesh_terms: D000418:Albumins / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D004337:Drug Carriers; D004357:Drug Synergism; D045604:Extracellular Fluid; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008279:Magnetic Resonance Imaging; D008297:Male; D053758:Nanoparticles; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D013267:Stilbenes; C058728:fosbretabulin; D017239:Paclitaxel
keywords: albumin-bound paclitaxel; combination therapy; combretastatin-A-4 phosphate; interstitial fluid pressure; tissue distribution