Enhancing Antitumor Efficacy by Simultaneous ATP-Responsive Chemodrug Release and Cancer Cell Sensitization Based on a Smart Nanoagent.

Xiao-Rong Song,Wenwu You,Huang-Hao Yang,Xueyuan Chen,Hanhan Guo,Datao Tu,Chun-Hua Lu,Shi-Hua Li,Juan Li

doi:10.1002/advs.201801201

Abstract

The exploitation of smart nanoagents based drug delivery systems (DDSs) has proven to be a promising strategy for fighting cancers. Hitherto, such nanoagents still face challenges associated with their complicated synthesis, insufficient drug release in tumors, and low cancer cell chemosensitivity. Here, the engineering of an adenosine triphosphate (ATP)‐activatable nanoagent is demonstrated based on self‐assembled quantum dots‐phenolic nanoclusters to circumvent such challenges. The smart nanoagent constructed through a one‐step assembly not only has high drug loading and low cytotoxicity to normal cells, but also enables ATP‐activated disassembly and controlled drug delivery in cancer cells. Particularly, the nanoagent can induce cell ATP depletion and increase cell chemosensitivity for significantly enhanced cancer chemotherapy. Systematic in vitro and in vivo studies further reveal the capabilities of the nanoagent for intracellular ATP imaging, high tumor accumulation, and eventual body clearance. As a result, the presented multifunctional smart nanoagent shows enhanced antitumor efficacy by simultaneous ATP‐responsive chemodrug release and cancer cell sensitization. These findings offer new insights toward the design of smart nanoagents for improved cancer therapeutics.

Highlights

Nanomaterials have gained numerous anticipated achievements in biomedicine, cated synthesis, insufficient drug release in tumors, and low cancer cell chemosensitivity
Characterizations through transmission electron microscopy (TEM), dynamic light scattering (DLS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) revealed the assembly of quantum dots (QDs) into QDs@tannic acid (TA) NCs with diameters of 55.1 ± 9.4 nm and a yield of about 80% (Figure 1c,g) due to that QDs can be linked by TA via the Zn-phenolic coordination between ZnS shell and multiple phenolic groups in TA.[14c]. Powder X-ray diffraction patterns indicated the preservation of crystallinity after forming NCs (Figure S1, Supporting Information)
We found that uridine triphosphate (UTP), cytidine triphosphate (CTP), and guanosine triphosphate (GTP) could trigger comparable enhancement of fluorescence relative to adenosine triphosphate (ATP) (Figure S4, Supporting Information), suggesting that the disassembly of NCs was stimulated by the metal ion–triphosphate coordination

Summary

Introduction

(DDSs) has proven to be a promising strategy for fighting cancers. Hitherto, such nanoagents still face challenges associated with their compli-. The nanoagent enabled ATP-responsive drug release and cellular ATP depletion, resulting in the increased cell chemosensitivity and enhanced therapeutic efficacy without causing side effects to normal cells. To design a multifunctional DDS with smart drug delivery and intracellular ATP depletion capabilities for improved chemotherapy.[13] we for the first time engineer the self-assembled quantum dots (QDs)-phenolic nanoclusters (NCs) as an smart nanoagent for enhancing anti-tumor efficacy by synergetic ATP-responsive chemodrug release and cancer cell sensitization (Scheme 1). Depleting intracellular ATP contents was found to effectively increase cancer cell chemosensitivity and enhance therapeutic efficacy of chemodrugs; it is challenging

Results and Discussion

Conclusion

Experimental Section

Conflict of Interest