Abstract
Polymeric drug vectors have shown great potentials in cancer therapy. However, intelligent controlled release of drugs has become a major challenge in nanomedicine research. Hypoxia-responsive polymeric micelles have received widespread attention in recent years due to the inherent hypoxic state of tumor tissue. In this study, a novel diblock polymer consisting of polyethylene glycol and poly[glutamic acid (3-(2-nitro-imidazolyl)-propyl)] was synthesized and self-assembled into hypoxia-responsive polymeric micelles for the controlled release of doxorubicin (DOX). The cell experiments demonstrated that DOX-loaded micelles had a stronger killing capacity on tumor cells under hypoxic conditions, while the blank micelles had good biocompatibility. All the experiments indicate that our hypoxia-responsive polymeric micelles have a great potential for enhanced cancer treatment.
Highlights
Cancer is a disease that endangers human life
After incubation with the micelles for 2 h under normoxic conditions, DOX was still mainly distributed in the cytoplasm. These results show that micelles can respond to hypoxia conditions and deliver drugs into the nucleus of tumor cells more quickly under hypoxic conditions
A hypoxia-responsive copolymer PEG-b-P(LGluNI) was successfully synthesized and self-assembled into micelles with DOX encapsulated in the hydrophobic core
Summary
Cancer is a disease that endangers human life. About 9.6 million people died because of cancer in 2018 according to American Cancer Society (Bray et al, 2018). Synthesis of PEG-b-P(LGlu-NI) (PEGN) 294.9 mg NI and 352.7 mg K2CO3 were dissolved in 10 mL of DMF and stirred for 10 min at room temperature. The solution was filtered with a 450-nm filter to remove large particles, and the solution was concentrated and washed three times using an ultrafiltration tube (MWCO = 100,000 Da) with physiological saline to obtain DOX-loaded micelles (PEGN/DOX). The DOX-loaded PEGN micelle solution was lyophilized, weighed, and dissolved in DMSO. MCF-7 cells were incubated overnight in 6-well plates at 37◦C and incubated with PEGN/DOX micelles for 2 h. Except that the MEM medium containing 100 μM CoCl2 was used to simulate the hypoxic environment in vivo, the experimental steps for the hypoxic group were the same as the above steps
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