pH-Controlled Intracellular in Situ Reversible Assembly of a Photothermal Agent for Smart Chemo-Photothermal Synergetic Therapy and ATP Imaging

• Published in: ACS applied materials & interfaces Vol. 11; no. 43; pp. 39624 - 39632
• Main Authors: Zhang, Jing, Cui, Yun-Xi, Feng, Xue-Nan, Cheng, Meng, Tang, An-Na, Kong, De-Ming
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 30.10.2019
• Subjects: adenosine triphosphate; Adenosine Triphosphate - metabolism; adverse effects; Animals; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; DNA; doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacokinetics; Doxorubicin - pharmacology; Female; Gold - chemistry; Gold - pharmacokinetics; Gold - pharmacology; HeLa Cells; Humans; Hydrogen-Ion Concentration; Hyperthermia, Induced; image analysis; lysosomes; MCF-7 Cells; medicine; Metal Nanoparticles - chemistry; Metal Nanoparticles - therapeutic use; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Imaging; nanogold; neoplasm cells; neoplasms; Neoplasms, Experimental - diagnosis; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - therapy; oligonucleotides; photochemotherapy; Phototherapy; renal clearance; Xenograft Model Antitumor Assays; intracellular in situ reversible assembly; doxorubicin; AuNP aggregate; ATP imaging; chemo-photothermal therapy
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.9b14186

To advance anti-tumor efficiency and lessen the adverse effect caused by nanodrug residues in the body, a smart nanoagent system is developed and successfully used in intracellular ATP imaging and in vivo chemo-photothermal synergetic therapy. The nanoagent system is facilely prepared using a DNA complex to modify gold nanoparticles (AuNPs). The DNA complex is formed by three oligonucleotides (ATP aptamer, rC-DNA, and rG-DNA). The CG-rich structure in a ternary DNA complex could be exploited for payload of chemotherapeutic medicine doxorubicin (DOX), thus making efficient DOX transport into the tumor site possible. In tumor cells, especially in acidic organelles (e.g., endosome and lysosome), DOX could be rapidly released via the dual stimuli of overexpressed ATP and pH. What is more, the specific recognition of a fluorescently labeled aptamer strand to ATP can achieve the intracellular ATP imaging. pH-controlled reversible folding and unfolding of intermolecular i-motif formed by C-rich strands can lead to intracellular in situ assembly of AuNP aggregates with high photothermal conversion efficiency and promote relatively facile renal clearance of AuNPs through the disassociation of the aggregates in extracellular environments. Experiments in vivo and vitro present feasibility for a synergetic chemo-photothermal therapy. Such an in situ reversible assembly strategy of a chemo-photothermal agent also presents a new paradigm for a smart and highly efficient disease treatment with reduced side effects.