Abstract Title:

Exogenous vitamin C boosts the antitumor efficacy of paclitaxel containing reduction-sensitive shell-sheddable micelles in vivo.

Abstract Source:

J Control Release. 2017 Feb 2. Epub 2017 Feb 2. PMID: 28163212

Abstract Author(s):

Yaqin Zhu, Xiuxiu Wang, Jian Zhang, Fenghua Meng, Chao Deng, Ru Cheng, Jan Feijen, Zhiyuan Zhong

Article Affiliation:

Yaqin Zhu


Slow drug release at the tumor tissue and poor tumor penetration are two big challenges for the successful application of nanosystems in tumor therapy. Here, we report that a high concentration of the natural reducing agent vitamin C (VC) triggers rapid extracellular PTX release from PTX-loaded shell-sheddable PEG-SS-PCL micelles (SSM) in tumors in vivo. An in vivo tolerance study showed that VC at a blood concentration of 40mM had little toxicity to nude mice. Notably, SSM rapidly disassembled and released the payloads (Cy5 or PTX) in response to 40mM VC. In vivo near-infrared imaging of tumor-bearing mice showed that with post-injection of VC to establish a blood concentration of 40mM, Cy5 was quickly released from the micelles and diffused deep into the tumor tissue. Biodistribution studies revealed that 6h after the injection of PTX-loaded micelles the highest tumor accumulation was reached, which was set as the injection time for VC. The antitumor efficacy of a combination therapy of PTX-loaded micelles and VC was evaluated in both MCF-7 and U87MG tumor models. In both tumor models, single injections of VC didn't show any antitumor effect, while sequential administration of PTX-loaded SSM and VC exhibited significantly higher tumor inhibition effects and better survival rates as compared to single treatment with PTX-loaded micelles, demonstrating that exogenous administration of VC effectively triggered the release of PTX from SSM in vivo. The combination of reduction-sensitive nanomedicines with exogenous VC appears a promising approach to achieve potent treatment of malignant tumors.

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