l-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells

Shiwei Niu, David H Bremner, Junzi Wu, Jianrong Wu, Haijun Wang, Heyu Li, Qianqian Qian, Hong Zheng, Limin Zhu

    Research output: Contribution to journalArticle

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    Abstract

    Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid - and thermally activated - PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.

    Original languageEnglish
    Pages (from-to)1275-1288
    Number of pages14
    JournalDrug Delivery
    Volume25
    Issue number1
    Early online date30 May 2018
    DOIs
    Publication statusPublished - 2018

    Fingerprint

    Paclitaxel
    Nanoparticles
    Apoptosis
    Breast Neoplasms
    Peptides
    Prodrugs
    Drug Delivery Systems
    Heterografts
    Permeability
    Neoplasms
    Drug Therapy
    Acids
    poly-N-isopropylacrylamide
    Therapeutics
    Growth
    Pharmaceutical Preparations

    Cite this

    Niu, Shiwei ; Bremner, David H ; Wu, Junzi ; Wu, Jianrong ; Wang, Haijun ; Li, Heyu ; Qian, Qianqian ; Zheng, Hong ; Zhu, Limin. / l-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells. In: Drug Delivery. 2018 ; Vol. 25, No. 1. pp. 1275-1288.
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    abstract = "Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5{\%}) and excellent encapsulation efficiency (74.3{\%}) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid - and thermally activated - PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.",
    author = "Shiwei Niu and Bremner, {David H} and Junzi Wu and Jianrong Wu and Haijun Wang and Heyu Li and Qianqian Qian and Hong Zheng and Limin Zhu",
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    l-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells. / Niu, Shiwei; Bremner, David H; Wu, Junzi; Wu, Jianrong; Wang, Haijun; Li, Heyu; Qian, Qianqian; Zheng, Hong; Zhu, Limin.

    In: Drug Delivery, Vol. 25, No. 1, 2018, p. 1275-1288.

    Research output: Contribution to journalArticle

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    AU - Niu, Shiwei

    AU - Bremner, David H

    AU - Wu, Junzi

    AU - Wu, Jianrong

    AU - Wang, Haijun

    AU - Li, Heyu

    AU - Qian, Qianqian

    AU - Zheng, Hong

    AU - Zhu, Limin

    PY - 2018

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    AB - Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid - and thermally activated - PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.

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