Ultrasound-responsive nanobubbles contained with peptide-camptothecin conjugates for targeted drug delivery.
To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to the tumor cells. The mean particle size of the prepared CPP-CPT NB was ∼200 nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP-CPT NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP-CPT NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.
a Department of Pharmacy , Wuhan General Hospital of Guangzhou Command , Wuhan , PR China.
Xiangyang
X
Xie
b Department of Clinical Laboratory , Huangshi Love & Health Hospital of Hubei Province , Huangshi , PR China , and.
Wen
W
Lin
a Department of Pharmacy , Wuhan General Hospital of Guangzhou Command , Wuhan , PR China.
Hui
H
Liu
b Department of Clinical Laboratory , Huangshi Love & Health Hospital of Hubei Province , Huangshi , PR China , and.
Jianping
J
Deng
a Department of Pharmacy , Wuhan General Hospital of Guangzhou Command , Wuhan , PR China.
Ying
Y
Chen
a Department of Pharmacy , Wuhan General Hospital of Guangzhou Command , Wuhan , PR China.
Hong
H
Liu
a Department of Pharmacy , Wuhan General Hospital of Guangzhou Command , Wuhan , PR China.
Xudong
X
Fu
c Beijing Institute of Pharmacology and Toxicology , Beijing , PR China.
Yang
Y
Yang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D014465:Ultrasonics
D000970:Antineoplastic Agents; D004337:Drug Carriers; D010455:Peptides; D002166:Camptothecin
Camptothecin; cell-penetrating peptide; drug delivery; nanobubbles; ultrasound