Leakage-free DOX/PEGylated chitosan micelles fabricated via facile one-step assembly for tumor intracellular pH-triggered release.
A general strategy was developed to fabricate the chitosan-based micelles as smart drug delivery system (DDS) for anti-cancer drug doxorubicin (DOX), via modulating the feeding ratio of PEG (PEG2000-CHO) and molecular weight of chitosan. Typically, benefiting from the solubility of chitosan in media with different pH values as an "off-on" switch, the DOX/CS100K-PEG2micelles possess spherical core with a narrow dispersed diameter of 64nm and regular shell with a thickness of 14nm in pH 7.4 PBS. Interestingly, the DOX/CS-PEG micelles exhibited drug leakage-free behavior in a physiological environment, with a cumulative release ratio of only 2.32% under pH 7.4 PBS, while achieving rapid drug release and a cumulative release ratio of 72.76% in the intracellular microenvironment. Moreover, the micelles transformed into the water-soluble CS100K-PEG2after the pH-triggered intracellular release of DOX, and it makes them easy to be biodegraded and eliminated by metabolic system. As revealed by MTT assays and CLSM images, DOX could be efficiently and rapidly transported into cell nuclei of tumor cells and showed significant cell inhibition. The simple fabrication and excellent properties make them intelligent and favorable on-demand DDS in cancer treatment.
State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Xubo
X
Zhao
State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Yuejun
Y
Yao
State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Kun
K
Tian
State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Tingting
T
Zhou
State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Xu
X
Jia
State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Jiagen
J
Li
State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China. Electronic address: pliu@lzu.edu.cn.
Peng
P
Liu
D000970:Antineoplastic Agents / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage*; D004318:Doxycycline / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D008823:Micelles; D014867:Water; D011092:Polyethylene Glycols; D004317:Doxorubicin; D048271:Chitosan; D004318:Doxycycline
Chitosan micelles; Controlled release; Drug delivery system; Drug leakage-free; pH-triggering