Intracellular Self‐Immolative Polyprodrug with Near‐Infrared Light Guided Accumulation and in Vivo Visualization of Drug Release

• Published in: Advanced materials (Weinheim) Vol. 34; no. 9; pp. e2109528 - n/a
• Main Authors: Cheng, Dong‐Bing, Zhang, Xue‐Hao, Chen, Si‐Yi, Xu, Xiao‐Xue, Wang, Hao, Qiao, Zeng‐Ying
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.03.2022
• Subjects: Accumulation; chemotherapy; Drug Liberation; Esterification; Humans; Hyperthermia; Infrared radiation; Infrared Rays; Irradiation; Materials science; Monitoring; Nanoparticles; Nanoparticles - therapeutic use; Neoplasms - drug therapy; photoacoustic imaging; Polyethylene glycol; Polyethylene Glycols - therapeutic use; polyprodrug; self‐assembly; Tumors; polyprodrug; self-assembly; photoacoustic imaging; chemotherapy
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.202109528

The selective accumulation and real‐time monitoring of drug release at tumor site are the key bottlenecks to the clinical translation of polyprodrug. Herein, an intracellular self‐immolative polyprodrug (PMTO) is exploited, which not only shows the enhanced cellular internalization and selective accumulation in tumor site under the mild hyperthermia triggered by laser irradiation, but also possesses the self‐monitoring drug release ability in vivo. The polyprodrug amphiphiles are synthesized by sequential esterification reaction, and hydrophilic poly(ethylene glycol) serves as blocking agent. On account of the mild hyperthermia produced by PMTO under the laser irradiation at tumor site, the cell membranous permeability increases, resulting in the enhanced cellular internalization and drug accumulation in tumor. After internalized by cells, the self‐immolative PMTO nanoparticles can release free mitoxantrone (MTO) in intracellular reductive environment, and ratiometric photoacoustic imaging based on distinct signals between MTO and PMTO is presented to trace the drug release in vivo. Finally, this self‐monitoring polyprodrug presents significant tumor suppression efficacy, which exhibits great potential for guiding the clinical medication in cancer treatment. An intracellular self‐immolative polyprodrug (PMTO) is developed, wherein the drug accumulation in tumor is significantly enhanced under laser‐triggered mild hyperthermia, and the drug release behavior is real‐time monitored by ratiometric photoacoustic signals. PMTO holds great potential for enhanced targeted chemotherapy efficacy as well as the visualization of drug release in vivo, guiding the clinical medication in cancer treatment.