Size-dependent chemosensitization of doxorubicin-loaded polymeric nanoparticles for malignant glioma chemotherapy

ABSTRACT

Chemotherapy is a traditional treatment method in clinical cancer treatment. However, it is limited due to the large toxic side effects of chemotherapeutics. Nanomedicines have shown great potential in the application of tumor therapy. The size of nanoparticles as a crucial factor in the enhanced permeability and retention (EPR) effect can be regulated for the enhanced chemotherapy. Therefore, we believe that regulation of nanoparticle size can be used as an effective sensitizer to enhance the therapeutic effect of chemotherapy drugs on tumors. Here, we prepared several nanoparticles of different hydrodynamic diameters commonly found in nanomedical applications by the diblock copolymer of methoxy polyethylene glycol-poly ($ϵ$‐caprolactone) (mPEG-PCL). The blood circulation effect and organ distribution in blood were detected by fluorescence labeled nanoparticles. We found that the small-sized nanoparticles exhibited much longer blood circulation time than the large-sized nanoparticles in vivo, and thus the nanoparticle concentration in the tumor tissue was relatively high. Systematic injection of the doxorubicin (DOX) loaded nanoparticles can effectively inhibit tumor growth. Compared to the free drug, tumor cells were much more sensitive to DOX loaded nanoparticles of small size. Our nano-drug delivery system has been proven to be safe and nontoxic in vivo and was suitable for use as a sensitizer in clinical oncology chemotherapy.

KEYWORDS:

• Malignant glioma
• doxorubicin-loaded nanoparticles
• chemosensitization
• tumor chemotherapy
• size-dependent

Acknowledgements

In this work, we are especially grateful to Yue Chen from Anhui Medical University for her help in the animal experiments.

Author contributions

All authors contributed to this work presented in this manuscript. All authors have given approval for the final version of the manuscript.

Availability of data and material

All data produced during the current study are available from the corresponding author on reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

Research experiments conducted in this article with animals or humans were approved by the Ethical Committee and responsible authorities of our research organization(s) following all guidelines, regulations, legal, and ethical standards as required for humans or animals.

Ethical compliance

Research experiments conducted in this article with animals or humans were approved by the Ethical Committee and responsible authorities of our research organization(s) following all guidelines, regulations, legal, and ethical standards as required for humans or animals.

Highlights

1. The regulation of nanoparticle size would trigger the sensitivity of tumor cells to chemotherapeutic drugs as a chemosensitizer.

2. The particle sizes can be controlled by adding hydrophobic polymer into the block polymer.

3. Nanoparticles of small sizes could effectively enhance the effect of chemotherapy and inhibit the growth of tumor.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.