Antitumor Effect of Paclitaxel-Loaded PEGylated Immunoliposomes Against Human Breast Cancer Cells

Tao, Yang; Choi, Min Koo; Cui, Fu De; Lee, Seung Jin; Chung, Suk Jae; Shim, Chang-Su; Kim, Dae Duk

doi:10.1007/s11095-007-9425-y

Cited by 112 publications

(65 citation statements)

References 40 publications

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“…It has been reported that SSL could spontaneously accumulate in solid tumors via the enhanced permeability and retention (EPR) effect through the passive targeting mechanism (15). Now, sterically stabilized liposomes containing paclitaxel (SSL-PTX) has been reported (16)(17)(18). The pharmacokinetic and antitumor efficiency of this SSL-PTX has been evaluated.…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenic Activity of Sterically Stabilized Liposomes Containing Paclitaxel (SSL-PTX): In Vitro and In Vivo

et al. 2010

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Abstract. The purpose of this present study was to evaluate the antiangiogenic activity of sterically stabilized liposomes containing paclitaxel (SSL-PTX). The SSL-PTX was prepared by the thin-film method. The release of paclitaxel from SSL-PTX was analyzed using a dialysis method. The effect of SSL-PTX on endothelial cell proliferation and migration was investigated in vitro. The antitumor and antiangiogenic activity of SSL-PTX was evaluated in MDA-MB-231 tumor xenograft growth in BALB/c nude mice. The release of paclitaxel from SSL-PTX was 22% within 24 h. Our in vitro results indicated that SSL-PTX could effectively inhibit the endothelial cell proliferation and migration at a concentrationdependent manner. We also observed that metronomic SSL-PTX induced marked tumor growth inhibition in MDA-MB-231 xenograft model via the antiangiogenic mechanism, unlike that in paclitaxel injection (Taxol) formulated in Cremophor EL (CrEL). Overall, our results suggested that metronomic chemotherapy with low-dose, CrEL-free SSL-PTX should be feasible and effective.

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Section: Introductionmentioning

confidence: 99%

Antiangiogenic Activity of Sterically Stabilized Liposomes Containing Paclitaxel (SSL-PTX): In Vitro and In Vivo

et al. 2010

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“…Cremophor EL has been reported to elicit various side effects in patients, including hypersensitivity, nephrotoxicity, and neurotoxicity [13]. Various formulations of PCT, such as polymeric micro/nanospheres [14,15], liposomes [16,17], microemulsions [18] and polymeric micelles [19][20][21] have been developed to increase the solubility of PCT, minimize its side effects, and decrease its systemic clearance.…”

Section: Introductionmentioning

confidence: 99%

Mixed PEG–PE/vitamin E tumor-targeted immunomicelles as carriers for poorly soluble anti-cancer drugs: Improved drug solubilization and enhanced in vitro cytotoxicity

Sawant

Torchilin

2008

European Journal of Pharmaceutics and Biopharmaceutics

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Two poorly soluble, potent anticancer drugs, paclitaxel and camptothecin, were successfully solubilized by mixed micelles of polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) and vitamin E. Drug containing micelles were additionally modified with anti-nucleosome monoclonal antibody 2C5 (mAb 2C5), which can specifically bring micelles to tumor cells in vitro. The optimized micelles had an average size of about 13-to-22 nm and the immuno-modification of micelles did not significantly change it. The solubilization of both drugs by the mixed micelles was more efficient than by micelles made of PEG-PE alone. Solubilization of camptothecin in micelles prevented also the hydrolysis of active lactone form of the drug to inactive carboxylate form. Drug loaded mixed micelles and mAb 2C5-immunomicelles demonstrated significantly higher in vitro cytotoxicity than free drug against various cancer cell lines.

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“…Passive targeted drug delivery utilizing the enhanced permeability and retention effect allows for increased deposition of nanovehicles at the site of a solid tumor. In contrast, active targeted drug delivery is achieved through covalent conjugation, on the nanocarrier surface, of a ligand or [5][6][7] Dendrimers are a family of nanosized, three-dimensional polymers characterized by a unique tree-like branching architecture. Polyamidoamine (PAMAM) dendrimers were the first commercialized dendrimers.…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

Ma¹,

Zhang²,

Ni³

et al. 2015

IJN

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Background Antibody-dendrimer conjugates have the potential to improve the targeting and release of chemotherapeutic drugs at the tumor site while reducing adverse side effects caused by drug accumulation in healthy tissues. In this study, trastuzumab (TMAB), which binds to human epidermal growth factor receptor 2 (HER2), was used as a targeting agent in a TMAB-polyamidoamine (PAMAM) conjugate carrying paclitaxel (PTX) specifically to cells overexpressing HER2. Methods TMAB was covalently linked to a PAMAM dendrimer via bifunctional polyethylene glycol (PEG). PTX was conjugated to PAMAM using succinic anhydride as a cross-linker, yielding TMAB-PEG-PAMAM-PTX. Dynamic light scattering and transmission electron microscopy were used to characterize the conjugates. The cellular uptake and in vivo biodistribution were studied by fluorescence microscopy, flow cytometry, and Carestream In Vivo FX, respectively. Results Nuclear magnetic resonance spectroscopy demonstrated that PEG, PTX, fluorescein isothiocyanate, and cyanine7 were conjugated to PAMAM. Ultraviolet-visible spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that TMAB was conjugated to PEG-PAMAM. Dynamic light scattering and transmission electron microscopy measurements revealed that the different conjugates ranged in size between 10 and 35 nm and had a spherical shape. In vitro cellular uptake demonstrated that the TMAB-conjugated PAMAM was taken up by HER2-overexpressing BT474 cells more efficiently than MCF-7 cells that expressed lower levels of HER2. Co-localization experiments indicated that TMAB-conjugated PAMAM was located in the cytoplasm. The in vitro cytotoxicity of TMAB-conjugated PAMAM was lower than free PTX due to the slow release of PTX from the conjugate. In vivo targeting further demonstrated that TMAB-conjugated PAMAM accumulated in the BT474 tumor model more efficiently than non-conjugated PAMAM. Conclusion TMAB can serve as an effective targeting agent, and the TMAB-conjugated PAMAM can be exploited as a potential targeted chemotherapeutic drug delivery system for tumors that overexpress HER2.

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Antitumor Effect of Paclitaxel-Loaded PEGylated Immunoliposomes Against Human Breast Cancer Cells

Cited by 112 publications

References 40 publications

Antiangiogenic Activity of Sterically Stabilized Liposomes Containing Paclitaxel (SSL-PTX): In Vitro and In Vivo

Antiangiogenic Activity of Sterically Stabilized Liposomes Containing Paclitaxel (SSL-PTX): In Vitro and In Vivo

Mixed PEG–PE/vitamin E tumor-targeted immunomicelles as carriers for poorly soluble anti-cancer drugs: Improved drug solubilization and enhanced in vitro cytotoxicity

Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

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