Polyvinylpyrrolidone Assisted One-Pot Synthesis of Size-Tunable Cocktail Nanodrug for Multifunctional Combat of Cancer

Abstract

Background

The in vivo barriers and multidrug resistance (MDR) are well recognized as great challenges for the fulfillment of antitumor effects of current drugs, which calls for the development of novel therapeutic agents and innovative drug delivery strategies. Nanodrug (ND) combining multiple drugs with distinct modes of action holes the potential to circumvent these challenges, while the introduction of photothermal therapy (PTT) can give further significantly enhanced efficacy in cancer therapy. However, facile preparation of ND which contains dual drugs and photothermal capability with effective cancer treatment ability has rarely been reported.

Methods

In this study, we selected curcumin (Cur) and doxorubicin (Dox) as two model drugs for the creation of a cocktail ND (Cur-Dox ND). We utilized polyvinylpyrrolidone (PVP) as a stabilizer and regulator to prepare Cur-Dox ND in a straightforward one-pot method.

Results

The size of the resulting Cur-Dox ND can be easily adjusted by tuning the charged ratios. It was noted that both loaded drugs in Cur-Dox ND can realize their functions in the same target cell. Especially, the P-glycoprotein inhibition effect of Cur can synergistically cooperate with Dox, leading to enhanced inhibition of 4T1 cancer cells. Furthermore, Cur-Dox ND exhibited pH-responsive dissociation of loaded drugs and a robust photothermal translation capacity to realize multifunctional combat of cancer for photothermal enhanced anticancer performance. We further demonstrated that this effect can also be realized in 3D multicellular model, which possibly attributed to its superior drug penetration as well as photothermal-enhanced cellular uptake and drug release.

Conclusion

In summary, Cur-Dox ND might be a promising ND for better cancer therapy.

Graphical Abstract

Keywords:

• one-pot synthesis
• size-tunable
• multifunctional
• cancer

Declaration of Generative AI and AI-Assisted Technologies in the Writing Process

During the preparation of this work, the authors used ChatGPT (https://chat.openai.com/) in order to improve readability and language. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Data Sharing Statement

Data will be made available on request.

Acknowledgments

The authors acknowledge the financial support from Jiangsu Key Research and Development Plan (Society Development (No. BE2022720); Science & Technology Support Program of Changzhou (No. CJ20235037); Natural Science Foundation of Jiangsu Province (No. BK20210851); Major Program of Science and Technology Project of Changzhou Health Commission (No. ZD202021); Postgraduate Research & Practice Innovation Program of Jiangsu Province (No. SJCX231464). The authors acknowledge the tissue slide preparation, staining, and imaging services provided by Record Biological Technology Co., Ltd. (Shanghai, China); the TEM imaging provided by Zhenjiang ZhuanBo Detection Technology Co., Ltd., and animal experiments service provided by Cavens animal center (Changzhou, China).

Disclosure

The authors report no conflicts of interest in this work.