A nanogel of on-site tunable pH-response for efficient anticancer drug delivery.
A smart, soft and small nanoparticulate drug carrier that can efficiently transport therapeutics into tumor cells to control the intracellular drug concentration will enable major advancements in cancer therapy. To facilitate a remote modulation of the intracellular pH-regulated drug release, we have designed a new class of pH-responsive chitosan-based nanogels (<200 nm) by the physical interpenetration of chitosan chains into a nonlinear poly(ethylene glycol) (nonlinear PEG) chain network. The resultant PEG-chitosan nanogels not only respond to the changes in environmental pH over the physiologically important range of 5.0-7.4, but - more importantly - also enable us to remotely modulate the pH response by external cooling/heating. The nanogel, as well as the nanogel loaded with a model anticancer drug 5-fluorouracil (5-FU), is capable of varying its surface charge from nearly neutral to positive around tumor extracellular pH (~6.0-6.2) to facilitate cell internalization. Subsequently, the significantly increased acidity in subcellular compartments (~5.0) can trigger 5-FU release from the endocytosed drug carriers. While this nanogel serving as a drug carrier exhibits a reduced toxicity in combined chemo-thermo treatments, it has shown significantly enhanced therapeutic efficacy in combined chemo-cryo treatments of the model B16F10 melanoma cells, indicating its great potential for cancer therapy.
State Key Laboratory for Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, People's Republic of China.
Ting
T
Zhou
Chuanfu
C
Xiao
Jiao
J
Fan
Shoumin
S
Chen
Jing
J
Shen
Weitai
W
Wu
Shuiqin
S
Zhou
D000327:Adsorption; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D048271:Chitosan; D004337:Drug Carriers; D005782:Gels; D006863:Hydrogen-Ion Concentration; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D011092:Polyethylene Glycols; D045663:Quantum Dots; D012709:Serum Albumin / Q000737:chemistry
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005782:Gels; D012709:Serum Albumin; D011092:Polyethylene Glycols; D048271:Chitosan