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Paclitaxel-Loaded, Folic-Acid-Targeted and TAT-Peptide-Conjugated Polymeric Liposomes: In Vitro and In Vivo Evaluation

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ABSTRACT

Objective

Folic acid and TAT peptide were conjugated on the octadecyl-quaternized, lysine-modified chitosan-cholesterol polymeric liposomes (FA-TATp-PLs) to investigate their potential feasibility for tumor-targeted drug delivery.

Methods

FA-TATp-PLs encapsulating paclitaxel or calcein were synthesized and characterized. Cellular uptake of PLs, FA-PLs, TATp-PLs and FA-TATp-PLs was studied by confocal laser scanning microscopy (CLSM) in folate receptor (FR)-positive KB nasopharyngeal epidermal carcinoma cells and FR-deficient A549 lung cancer cells. In vitro and in vivo antitumor activity of paclitaxel-loaded FA-TATp-PLs were also evaluated in KB and A549 cells as well as in a murine KB xenograft model.

Results

Our data showed that 80% paclitaxel released from FA-TATp-PLs in 2 weeks. Different from other various PLs, CLSM analyses showed that FA-TATp-PLs had a significantly high efficient intracellular uptake in both KB and A549 cells. These data revealed the targeting effects of folate decoration, the transmembrane ability of TAT peptide as well as a synergistic interaction between them. In addition, paclitaxel-loaded FA-TATp-PLs exhibited a more superior antitumor effect in vitro and in vivo as compared to that with Taxol®.

Conclusions

FA-TATp-PLs possessing both targeting effect and transmembrane ability may serve as a promising carrier for the intracellular delivery of therapeutic agents.

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Abbreviations

DAPI:

4,6-Diamidino-2-phenylindole

DLS:

dynamic light scattering

DMSO:

dimethyl sulfoxide

DTT:

dithiothreitol

ER:

encapsulation rate

FA:

folic acid

FR:

folate receptor

HPLC:

high performance liquid chromatography

LE:

loading efficiency

MTT:

3-[4,5-dimethylthiazol-2-yl]-2,5-diphenltetrazolium bromide

MW:

molecular weight

OQLCS:

octadecyl-quaternized lysine modified chitosan

PBS:

phosphate-buffered saline

PLs:

Polymeric liposomes

PTX:

paclitaxel

SD:

standard deviation

SPDP:

N-succinimidyl-3-(2-pyridyldithio) propionate

TATp:

transactivating transcriptional activator peptide

TEM:

transmission electron microscopy

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ACKNOWLEDGMENTS

The study was supported by the National High Technology Development Project (the “863” project, Grant No. 2007AA021802, No. 2007AA021808, No. 2006AA02A249).

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Authors and Affiliations

  1. The Key Laboratory of Breast Cancer Prevention and Therapy Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Peiqi Zhao, Shuzhen Cao, Fei Zhang & Ruifang Niu

  2. Institute of Nanobiotechnology, School of Materials Science and Engineering, Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Tianjin, 300072, China

    Hanjie Wang & Jin Chang

  3. Center for Advanced Research in Environmental Genomics (CAREG) Department of Biology and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada, K1N 6N5

    Man Yu

Authors
  1. Peiqi Zhao
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  2. Hanjie Wang
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  4. Shuzhen Cao
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  5. Fei Zhang
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  6. Jin Chang
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  7. Ruifang Niu
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Correspondence to Jin Chang or Ruifang Niu.

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Zhao, P., Wang, H., Yu, M. et al. Paclitaxel-Loaded, Folic-Acid-Targeted and TAT-Peptide-Conjugated Polymeric Liposomes: In Vitro and In Vivo Evaluation. Pharm Res 27, 1914–1926 (2010). https://doi.org/10.1007/s11095-010-0196-5

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  • DOI: https://doi.org/10.1007/s11095-010-0196-5

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