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Hyaluronic Acid Layer-By-Layer (LbL) Nanoparticles for Synergistic Chemo-Phototherapy

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Abstract

Purpose

The aim of this study was to design hyaluronic acid (HA) layer-by-layer (LbL) nanoparticles, which carried paclitaxel (PTX) and Indocyanine green (ICG) to both tumor cells and tumor associated cells to achieve synergistic chemo-photothermal therapeutic effect.

Methods

The LbL-engineered nanoparticles (PDIH) were prepared by dopamine self-polymerization on PTX nanocrystal to form thin, surface-adherent polydopamine (PDA) films, which subsequently absorbed ICG and HA. The tumor cell and tumor associated cell targeting and antitumor efficacy of PDIH were investigated both in vitro an in vivo using 4 T1 murine mammary cancer cell lines and mice bearing orthotopic 4 T1 breast tumor.

Results

PDIH presented a long-rod shape in TEM and showed enhanced photothermal effect and cytotoxicity upon NIR laser irradiation both in vitro and in vivo. PDIH also displayed high target ability to CD44 overexpressed tumor cells and tumor associated cells mediated by HA. In vivo antitumor study indicated that PDIH therapeutic strategy could achieve remarkable antitumor efficacy.

Conclusion

PDIH showed excellent tumor-targeting property and chemo-photothermal therapeutic efficacy.

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Abbreviations

CLSM:

Confocal laser scan microscopy

FDA:

The US food and drug administration

FITC:

Fluorescein-5(6)-isothiocyanate

HA:

Hyaluronic acid

ICG:

Indocyanine green

LbL:

Layer-by-layer

MTT:

Methyl thiazolyl tetrazolium

NIR:

Near infrared

PAI:

Photoacoustic imaging

PDA:

Polydopamine

PTX:

Paclitaxel

TAF:

Tumor associated fibroblast

TAM:

Tumor associated macrophage

TEM:

Transmission electron microscopy

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Acknowledgments and Disclosures

This work was supported by the Fundamental Research Funds for the Central Universities (20826041A4343) and China Postdoctoral Science Foundation (2017 M623051). No conflict of interest exits in the submission of this manuscript.

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Authors and Affiliations

  1. Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Block 3 Southern Renmin Road, Chengdu, 610041, China

    Juan Zhao, Chuchu Zhou, Qin Yang, Xu Song & Tao Gong

  2. School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, 15217, USA

    Zhuoya Wan

  3. Department of Clinical Pharmacy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, People’s Republic of China

    Jianxia Dong

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  1. Juan Zhao
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  2. Zhuoya Wan
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  4. Qin Yang
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  5. Jianxia Dong
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  6. Xu Song
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  7. Tao Gong
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Correspondence to Xu Song.

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Zhao, J., Wan, Z., Zhou, C. et al. Hyaluronic Acid Layer-By-Layer (LbL) Nanoparticles for Synergistic Chemo-Phototherapy. Pharm Res 35, 196 (2018). https://doi.org/10.1007/s11095-018-2480-8

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