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

Abstract

Cheng Wang,1,* Jiaoyang Pan,1,* Shaoqing Chen,2 Lin Qiu,1 Huaanzi Hu,1 Li Ji,3 Jianhao Wang,1 Wenjia Liu,4 Xinye Ni2 1School of Pharmacy, Changzhou University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 3Department of Otorhinolaryngology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 4Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjia Liu; Xinye Ni, Email [email protected]; [email protected]: 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. Keywords: one-pot synthesis, size-tunable, multifunctional, cancer

Keywords

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