Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects

• Published in: Journal of nanobiotechnology Vol. 22; no. 1; p. 2
• Main Authors: Jiang, Yifan, Chen, Hongjian, Lin, Tao, Zhang, Chao, Shen, Jiaxin, Chen, Jifan, Zhao, Yanan, Xu, Wen, Wang, Guowei, Huang, Pintong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.01.2024; BioMed Central; BMC
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Analysis; Animal models; Animals; Anticancer properties; Antineoplastic Agents - therapeutic use; Antineoplastic drugs; Antitumor activity; Antitumor agents; Apoptosis; Cancer; Cancer targeting therapy; Cancer therapies; Cell Line, Tumor; Chemical properties; Chemotherapy; Colon cancer; Colonic Neoplasms - diagnostic imaging; Colonic Neoplasms - drug therapy; Complications and side effects; Cytotoxicity; Dosage and administration; Drug delivery; Drug delivery systems; Drug targeting; Drug therapy; Drugs; Efficiency; Equilibrium; Feasibility; Glycerol; Health aspects; Hepatocellular carcinoma; Humans; Irinotecan; Irradiation; Ligands; Lipids; Liposome; Liposomes; Lung cancer; Mice; Nanoparticles - metabolism; Oncology, Experimental; Pancreatic cancer; Patient compliance; Pharmaceutical research; Photochemotherapy; Photosensitizing Agents - therapeutic use; Polyethylene glycol; Prodrug; Prodrugs; Prodrugs - pharmacology; Prodrugs - therapeutic use; Prognosis; Reactive oxygen species; Reactive Oxygen Species - metabolism; Side effects; Stimuli-responsive drug delivery; Topotecan; Toxicity; Tumor Microenvironment; Tumors; Ultrasonic imaging; Ultrasonic waves; Ultrasound; Vehicles; China; Liposome; Prodrug; Cancer targeting therapy; Ultrasound; Stimuli-responsive drug delivery
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-023-02195-5

Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers. To address these problems, a radically different strategy is proposed that can leave the off-targeted drugs inactive but activate the tumor-distributed drugs for cancer-targeting therapy in a tumor microenvironment-independent manner. The feasibility and effectiveness of this strategy is demonstrated by developing an ultrasound (US)-activated prodrug-loaded liposome (CPBSN38L) comprising the sonosensitizer chlorin e6 (Ce6)-modified lipids and the prodrug of pinacol boronic ester-conjugated SN38 (PBSN38). Once CPBSN38L is accumulated in the tumor and internalized into the cancer cells, under US irradiation, the sonosensitizer Ce6 rapidly induces extensive production of intracellular reactive oxygen species (ROS), thereby initiating a cascade amplified ROS-responsive activation of PBSN38 to release the active SN38 for inducing cell apoptosis. If some of the injected CPBSN38L is distributed into normal tissues, the inactive PBSN38 exerts no pharmacological activity on normal cells. CPBSN38L exhibited strong anticancer activity in multiple murine tumor models of colon adenocarcinoma and hepatocellular carcinoma with no chemotherapy-induced side effects, compared with the standard first-line anticancer drugs irinotecan and topotecan. This study established a side-effect-evitable, universal, and feasible strategy for cancer-targeting therapy.