Active targeting liposome-PLGA composite for cisplatin delivery against cervical cancer.

Cisplatin (Cis) is a widely used chemotherapeutic drug for cancer treatment. However, toxicities and drug resistance limit the use of cisplatin. This study was aimed to improve cisplatin delivery using a targeting strategy to reduce the toxicity. In the present study, combinations of poly lactic-co-glycolic acids (PLGA) and liposomes were used as carriers for cisplatin delivery. In addition, to target the nanoparticle towards tumor cells, the liposome was conjugated with Avastin®, an anti-VEGF antibody. Cisplatin was loaded into PLGA using the double emulsion solvent evaporation method and further encapsulated in an Avastin® conjugated liposome (define herein as L-PLGA-Cis-Avastin®). Their physicochemical properties, including particle size, ζ-potential, encapsulation efficiency and drug release profiles were characterized. In addition, a study of the efficiency of tumor targeted drug delivery was conducted with cervical tumor bearing mice via intravenous injection. The therapeutic effect was examined in a 3D spheroid of SiHa cell line and SiHa cells bearing mice. The L-PLGA-Cis-Avastin® prompted a significant effect on cell viability and triggered cytotoxicity of SiHa cells. A cell internalization study confirmed that the L-PLGA-Cis-Avastin® had greater binding specificity to SiHa cells than those of L-PLGA-Cis or free drug, resulting in enhanced cellular uptake. Tumor targeting specificity was finally confirmed in xenograft tumors. Taken together, this nanoparticle could serve as a promising specific targeted drug for cervical cancer treatment.

Phospholipid-chitosan hybrid nanoliposomes promoting cell entry for drug delivery against cervical cancer.

This study emphasizes the development of a novel surface modified liposome as an anticancer drug nanocarrier. Quaternized N,O-oleoyl chitosan (QCS) was synthesized and incorporated into liposome vesicles, generating QCS-liposomes (Lip-QCS). The Lip-QCS liposomes were spherical in shape (average size diameter 171.5±0.8nm), with a narrow size distribution (PDI 0.1±0.0) and zeta potential of 11.7±0.7mV. In vitro mucoadhesive tests indicated that Lip-QCS possesses a mucoadhesive property. Moreover, the presence of QCS was able to induce the cationic charge on the surface of liposome. Cellular internalization of Lip-QCS was monitored over time, with the results revealing that the cell entry level of Lip-QCS was elevated at 24h. Following this, Lip-QCS were then employed to load cisplatin, a common platinum-containing anti-cancer drug, with a loading efficiency of 27.45±0.78% being obtained. The therapeutic potency of the loaded Lip-QCS was investigated using a 3D spheroid cervical cancer model (SiHa) which highlighted their cytotoxicity and apoptosis effect, and suitability as a controllable system for sustained drug release. This approach has the potential to assist in development of an effective drug delivery system against cervical cancer.

Novel mutations in cholangiocarcinoma with low frequencies revealed by whole mitochondrial genome sequencing.

BACKGROUND: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. MATERIALS AND METHODS: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. RESULTS: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. CONCLUSIONS: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.

Overexpression of claudin-4 in cholangiocarcinoma tissues and its possible role in tumor metastasis.

Claudin-4 (CLDN4) is a tight junction protein that forms apical junctional complexes in epithelial and endothelial cellular sheets. Acting as a barrier and control of permeability are the general functions of tight junction proteins contributing to tissue homeostasis, paracellular ion flux, and cell-cell contact. In this study, we immunohistochemically examined CLDN4 expression in liver fluke-associated cholangiocarcinomas (CCAs) with tissue microarrays. Regardless of the histological type and gross type of cancer, high expression of CLDN4 was noted in precancerous hyperplastic/dysplastic biliary epithelia and CCA. To investigate functional roles of CLDN4 in cancer progression, the effects of CLDN4 suppression by siRNA on cell proliferation, migration and invasion were investigated in two CCA cell lines, KKU-M139 and KKU-M213. Suppression of CLDN4 expression did not alter cell proliferation but caused significant reduction of cell migration and invasion by both CCA cell lines. Our results suggest that over-expressed CLDN4 may promote CCA expansion and metastasis.