Current treatments including surgery, chemotherapy, and radiotherapy remain to have KU55933 clinical trial several disadvantages, thereby often leading to recurrence [2]. Two prophylactic HPV vaccines (Gardasil and Cervarix) [3] can prevent most high-risk HPV infections and minimize the consequences of HPV-associated diseases. However, these vaccines are effective only in adolescents with no history of previous HPV infection and have not shown any therapeutic effects against current HPV infections or associated lesions [3]. Thus, there is an urgent need to develop new specific drugs and methods to treat cervical cancer. Tumor necrosis factor-related
apoptosis-inducing ligand (TRAIL) is a type 2 transmembrane protein that causes apoptosis of target cells through the extrinsic apoptosis pathway. TRAIL selleck products belongs to a member of the tumor necrosis factor superfamily including tumor QNZ order necrosis factor and Fas ligand [4]. The binding of tumor necrosis factor and Fas ligand leads to the damage of normal tissues
in addition to their proapoptotic effect on transformed cells [5, 6], thus limiting their clinical applications. Conversely, TRAIL is able to selectively induce apoptosis in transformed cells but not in most normal cells [4, 7, 8], making it a promising candidate for tumor therapy. Furthermore, tumor growth and progression rely upon angiogenesis [9–11]. Consequently, antiangiogenesis has also emerged as an attractive new strategy in the treatment of cancer [12–16]. Among these agents, endostatin, a 20-kDa C-terminal proteolytic fragment of collagen XVIII, has received the greatest attention Methisazone [17]. It was found not only to be a potent inhibitor of angiogenesis in vitro, but also to have significant antitumor effects in a variety of xenograft-based cancer models and clinical trials [17]. These promising results lead to the rapid advance of this agent into the clinical test [17, 18]. For instance, endostatin enhanced the anticancer effect of CCRT in a mouse xenograft model of cervical cancer [19]. Furthermore, the use of endostatin in combination with other anticancer agents
such as gemcitabine had synergistic antitumor activities [20]. Delivery of therapeutic agents by gene therapy has been extensively studied in a broad range of diseases [21–24]. However, a recurrent problem in these therapies is the efficient delivery of the therapeutic DNA, RNA, or siRNA to the target cells. The key technological impediment to successful gene therapy is vector optimization. Thus, several strategies are being investigated to circumvent this problem such as adeno- or adeno-associated viruses [25]. However, clinical trials have demonstrated substantial obstacles to their use, such as immunogenicity and inflammatory potential [26]. Various non-viral delivery systems, including liposomes [27], dendrimers [28], polycationic polymers [29, 30], and polymeric nanoparticles (NPs) [31] are under development to reduce or avoid immunogenicity and associated risks of toxicity [32].
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