Abstract
In vitro studies had shown that C-Phycocyanin (C-PC) inhibited cervical cancer HeLa cells growth. We constructed C-PC/CMC-CD55sp nanospheres using C-PC, Carboxymethyl Chitosan (CMC), and CD55 ligand peptide (CD55sp) to allow for targeted antitumor effects against HeLa cells in vitro and in vivo. The characteristics of the nanospheres were determined using FTIR, electron microscopy, and laser particle size analysis. Flow cytometry, laser confocal microscopy and small animal imaging system showed the targeting of C-PC/CMC-CD55sp nanospheres on HeLa cells. Subsequently, the proliferation and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), flow cytometry, TUNEL assay and electron microscopy. The expression of the apoptosis-related protein was determined using western blot. The stainings of Hematoxylin and Eosin (HE) were employed to evaluate the cell condition of tumor tissue sections. The cytokines in the blood in tumor-bearing nude mice was determined using ELISA. These results showed that C-PC/CMC-CD55sp nanospheres were successfully constructed and targeted HeLa cells. The constructed nanospheres were more effective than C-PC alone in inhibiting the proliferation and inducing apoptosis in HeLa cells. We also found that C-PC/CMC-CD55sp nanospheres had a significant inhibitory effect on the expression of antiapoptotic protein Bcl-2 and a promotion on the transformation of caspase 3 to cleaved caspase 3. C-PC/CMC-CD55sp nanospheres played an important role in tumor suppression, reduced the expression TGF-β, and increased IL-6 and TNF-α. This study demonstrates that the constructed new C-PC/CMC-CD55sp nanospheres exerted targeted antitumor effects in vivo and in vitro which provided a novel idea for application of C-PC, and provided experimental basis for comprehensive targeted treatment of tumors.
Highlights
Screening and vaccination are the most common methods to prevent cervical cancer (Torre et al, 2015), and chemotherapy is a first-line treatment option for patients with cervical cancer
Accumulation of the nanospheres in the liver and the spleen may have been related to drug metabolism and the reticuloendothelial phagocytosis (Figure 3C). These results indicated that C-PC/Carboxymethyl Chitosan (CMC)-CD55sp nanospheres were targeted to tumors, and that CD55sp may be an effective tumor targeting factor
We found that C-PC, C-PC/CMC, and C-PC/CMC-CD55sp increased apoptosis in have been used to target cervical cancer (HeLa) cells, and C-PC/CMC-CD55sp induced apoptosis to the greatest extent by TUNEL assay (Figures 5A, B) and flow cytometry analysis (Figures 5C, D)
Summary
Screening and vaccination are the most common methods to prevent cervical cancer (Torre et al, 2015), and chemotherapy is a first-line treatment option for patients with cervical cancer. Tumor-targeted drug delivery systems represent an important advancement in cancer therapy. These formulations can deliver effective antitumor drugs or selectively to tumor tissues, which allows for control of drug dosing at specific physiological sites. Nanospheres have been conjugated to a monoclonal antibody against Trophoblast cell surface antigen 2 (TROP2), which is a protein abundant on the surface of HeLa cells. This formulation selectively killed cervical cancer cells through induction of apoptosis and DNA damage (Liu T. et al, 2014). Folic acid–conjugated albumin nanospheres have been developed to target drugs to cervical cancer cells, and to reduce side effects (Shen et al, 2011)
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