Synergistic mediation of tumor signaling pathways in hepatocellular carcinoma therapy via dual-drug-loaded pH-responsive electrospun fibrous scaffolds

Ziming Yuan, Xin Zhao, Jingwen Zhao, Guoqing Pan, Wangwang Qiu, Xiaohu Wang, Yueqi Zhu, Qi Zheng, Wenguo Cui

Research output: Journal article publicationJournal articleAcademic researchpeer-review

21 Citations (Scopus)

Abstract

With the understanding of tumorigenesis, the tumor-infiltrating inflammatory cells, which could contribute to carcinogenesis, have greatly drawn public attention. We hypothesized that controlling inflammation in the initial stage along with antitumor activity for a relatively long term could prevent tumor recurrence. Herein, we designed a novel electrospun composite poly(l-lactide) (PLLA) fibrous scaffold, which contained sodium bicarbonate (SB) and doxorubicin (DOX) inside mesoporous silica particles (MSNs) to achieve long-term pH-sensitive DOX release and ibuprofen (IBU) outside MSNs to achieve initial short-term release. This construct was found to exhibit an initial burst release of IBU at an early stage and sustained the release of DOX at a relatively later stage. In vivo results showed that when the fibrous scaffold was implanted in a liver-tumor-bearing nude mouse, the mouse lifespan was prolonged to 1.5 times higher than that when implanted with scaffolds with no IBU or SB. Moreover, the residual tumor treated with PLLA-(MSN/DOX-SB)-IBU fibers demonstrated considerable signs of apoptosis and large areas of necrosis over a 10 week examination period. By combining the in vitro and in vivo experiments, the results have suggested that this dual drug delivery system could effectively inhibit inflammation in the initial stage and prevent tumor recurrence for a relatively long term, and it may find application as a local implantable scaffold to treat a tissue defect after tumor resection.
Original languageEnglish
Pages (from-to)3436-3446
Number of pages11
JournalJournal of Materials Chemistry B
Volume3
Issue number17
DOIs
Publication statusPublished - 7 May 2015
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

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