The stimuli-responsive nano-carriers are at the forefront of research in nanotechnology and materials science. These advanced systems are designed to alter their physicochemical properties upon exposure to specific stimuli, enabling controllable and targeted delivery of therapeutic agents. Nevertheless, limited endosomal escape reduces the drug bioavailability in clinical use. We herein report azobenzene (Azo)-based liposomes, prepared by co-assembling the photoisomerizable cationic Azo lipids and helper lipids, which achieve controllable doxorubicin (Dox) release and enhanced cytosolic transport upon light irradiation. Azo lipids undergo reversible isomerization between cis-isomers and trans-isomer when received UV and visible (Vis) light irradiation, causing liposomal membrane permeability changes for controlled drug release. Moreover, the nanomechanical action created by the isomerization of Azo lipids promotes the endosomal escape of the liposomes. DSPC-Azo liposomes, with minimal Dox leakage, showed significant tumor cell killing upon irradiation. For in vivo study, we coencapsulated the upconverting nanoparticles (UCNPs), which can convert the near-infrared (NIR) light into UV/Vis emissions, facilitating Azo units activation. UCNP/Dox-loaded DSPC-Azo liposomes inhibited tumor growth under NIR irradiation in a 4T1 tumor-bearing mouse model.
[1]Tianjin Med Univ Canc Inst & Hosp, Tianjin Med Univ Canc Inst,Minist Educ,Natl Clin R, Tianjins Clin Res Ctr Canc,Key Lab Breast Canc Pre, Dept VIP Ward,Key Lab Canc Prevent & Therapy Tianj, Tianjin 300060, Peoples R China.
[2]Chinese Acad Med Sci & Peking Union Med Coll, Tianjin Inst Hlth Sci,State Key Lab Adv Med & Devi, Tianjin Key Lab Radiat Med & Mol Nucl Med, Inst Radiat Med,State Key Lab Adv Med Mat & Device, Tianjin 300192, Peoples R China.
[3]Cornell Univ, Meinig Sch Biomed Engn, Ithaca, NY 14853 USA.
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