Tumor-Targeting and Microenvironment-Responsive Smart Nanoparticles for Combination Therapy of Antiangiogenesis and Apoptosis
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- 作者：Shixian Huang ; Kun Shao ; Yang Liu ; Yuyang Kuang ; Jianfeng Li ; Sai An ; Yubo Guo ; Haojun Ma ; Chen Jiang
- 刊名：ACS Nano
- 出版年：2013
- 出版时间：March 26, 2013
- 年：2013
- 卷：7
- 期：3
- 页码：2860-2871
- 全文大小：958K
- 年卷期：v.7,no.3(March 26, 2013)
- ISSN：1936-086X
文摘
Tumor microenvironment, such as the lowered tumor extracellular pH (pHe) and matrix metalloproteinase 2 (MMP2), has been extensively explored, which promotes the development of the microenvironment-responsive drug delivery system. Utilizing these unique features, an activatable cell-penetrating peptide (designated as dtACPP) that is dual-triggered by the lowered pHe and MMP2 has been constructed, and a smart nanoparticle system decorating with dtACPP has been successfully developed, which could dual-load gene drug and chemotherapeutics simultaneously. After systemic administration, dtACPP-modified nanoparticles possess passive tumor targetability via the enhanced permeability and retention effect. Then dtACPP would be activated to expose cell-penetrating peptide to drive the nanoparticles鈥?internalization into the intratumoral cells. As angiogenesis and tumor cells might be mutually improved in tumor growth, so combining antiangiogenesis and apoptosis is meaningful for oncotherapy. Vascular endothelial growth factor (VEGF) is significant in angiogenesis, and anti-VEGF therapy could decrease blood vessel density and delay tumor growth obviously. Chemotherapy using doxorubicin (DOX) could kill off tumor cells efficiently. Here, utilizing dtACPP-modified nanoparticles to co-deliver plasmid expressing interfering RNA targeting VEGF (shVEGF) and DOX (designated as dtACPPD/shVEGF鈥揇OX) results in effective shutdown of blood vessels and cell apoptosis within the tumor. On the premise of effective drug delivery, dtACPPD/shVEGF鈥揇OX has demonstrated good tumor targetability, little side effects after systemic administration, and ideal antitumor efficacy.