Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 35, Pages 31681-31692Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b10950
Keywords
ROS-responsive; photodynamic therapy; chemotherapy; drug delivery; cell penetrating
Funding
- National Natural Science Foundation of China (NNSFC) [21674104, 21875234]
- CAS-TWAS presidents Fellowship
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In situ modulation of the surface properties on the micellar drug delivery nanocarriers offers an efficient method to improve the drug delivery efficiency into cells while maintaining stealth and stability during blood circulation. Light has been demonstrated to be a temporally and spatially controllable tool to improve cellular internalization of nanoparticles. Herein, we develop reactive oxygen species (ROS)-responsive mixed polymeric micelles with photoinduced exposure of cell-penetrating moieties via photodynamic ROS production, which can facilitate cellular internalization of paclitaxel (PTX) and chlorin e6 (Ce6)-coloaded micelles for the synergistic effect of photodynamic and chemotherapy. The thioketal-bond-linked block polymers poly(epsilon-caprolactone)-TL-poly(N,N-dimethylacrylamide) (PCL-TL-PDMA) with a long PDMA block are used to self-assemble into mixed micelles with PCL-b-poly(2-guanidinoethyl methacrylate) (PCL-PGEMA) consisting of a short PGEMA block, which are further used to coencapsulate PTX and Ce6. After intravenous injection, prolonged blood circulation of the micelles guarantees high tumor accumulation. Upon irradiation by 660 nm light, ROS production of the micelles by Ce6 induces cleavage of PDMA to expose PGEMA shells for significantly improved cellular internalization. The combination of photodynamic therapy and chemotherapy inside the tumor cells achieves improved antitumor efficacy. The design of ROS-responsive mixed polymeric nanocarriers represents a novel and efficient approach to realize both long blood circulation and high-efficiency cellular internalization for combined photodynamic and chemotherapy under light irradiation.
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