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Osteosarcoma is the bone tumor that most commonly affects children and teenagers with low survival rate because of metastatic relapse or recurrence. Cisplatin is a first-line chemotherapy for osteosarcoma. However, severe side effects limit its use in clinic. Selenium (Se) is an anticarcinogen that can protect normal tissues from side effects of chemotherapy. In this study, nanoparticles were used to co-deliver cisplatin and Se in a synergistic combination. Se-doped and lipid-coated calcium carbonate nanoparticles loaded with cisplatin (Pt/Se@CaCO3 NPs) were prepared by a reverse microemulsion method. The NPs delivered cisplatin and Se to tumour cells at an optimal synergistic ratio of 1:1 (mol/mol) both in vitro and in an osteosarcoma xenograft model. These results demonstrate that Pt/Se@CaCO3 NPs have great prospects for the osteosarcoma therapy.

Multidrug resistance to chemotherapeutic drugs is a major obstacle to breast cancer treatment. In this study, doxorubicin (DOX) and imatinib (IM) were co-loaded into folate receptor targeted (FR-targeted) pH-sensitive liposomes (denoted as FPL-DOX/IM) to fulfill intracellular acid-sensitive release and reverse drug resistance. FPL-DOX/IM could maintain stability in blood circulation with approximate diameters of 100 nm and rapidly release encapsulated drugs in tumor acidic microenvironment. Moreover, the IM in combination therapy could overcome chemoresistance associated with DOX effectively by inhibiting ABC transporter function and improving chemotherapy sensitivity. The designed liposomes co-loaded with DOX and IM significantly enhanced anti-tumor effects both in vitro and in vivo. These findings suggest that FPL-DOX/IM provides a novel strategy to improve chemotherapeutic efficacy against MDR tumors.

Hepatocellular carcinoma (HCC) continues to be a leading cause of cancer related death in the world. Conventional chemotherapeutic agents such as cisplatin (CDDP) have an unsatisfactory efficacy on HCC due to the poor response, severe toxicity and drug resistance. Curcumin (CUR) could improve the chemosensitivity of HCC to chemotherapy drugs by regulating a variety of signaling pathways. Herein, we describe a combination strategy using co-loaded liposomes to effectively deliver and release CDDP and curcumin (CUR) to HCC for overcoming the unsatisfactory clinical outcome of CDDP monotherapy. In the study, CDDP and CUR co-loaded liposomes (CDDP/CUR-Lip) were prepared by a reverse microemulsion and film dispersion method and their average particle size 294.6 ± 14.8 nm with uniform size distribution. In vitro study showed that the nano sized CDDP/CUR-Lip could synchronously release both CDDP and CUR to achieve the synergistic effect against HCC cells based on the optimal ratio (1:8) of both drugs. Compared with free drug or encapsulated mono-drug therapy, CDDP/CUR-Lip demonstrated the higher anti-tumor activity in vitro against HepG2 cells with the IC50 of 0.62 μM. In addition, CDDP/CUR-Lip also increased intracellular ROS level during the HCC cells treatment. Furthermore, compared with single drug formulation, CDDP/CUR-Lip showed the elongated retention time (t1/2 = 2.38 h) and improved antitumor effect in both mouse hepatoma H22 and human HCC HepG2 xenograft models with reduced side effects. In conclusion, CDDP/CUR-Lip provide an attractive and potential strategy to attain synergistic effect of CDDP and CUR for the treatment of HCC.

Bmi-1 is a gene related to malignant transformation in hepatocellular carcinoma (HCC). The liver cancer cells developed the ability to tolerate CDDP treatment with the elevation of Bmi-1. Bmi-1 is also an oncogene promoting malignance of tumor and an anti-cancer target in many studies. Herein, a biocompatible nanocarrier was designed in the study to deliver a chemotherapeutical agent CDDP and Bmi-1 siRNA to kill cancer cells and silence drug resistance related gene simultaneously. Calciumphosphate (CaP) was applied to coat both nanoplatin cores and siRNA as a shell for the purpose of delivering cargos to the cytosol of the tumor cells. Nanoplatin and siRNA co-loaded CaP nanoparticles (NPSC) enhanced cell uptake of CDDP and showed elevated drug accumulation in tumor. NPSC achieved considerable anti-cancer efficacy and counter-regulated drug tolerance, therefore, warranted a further investigation as a novel therapeutic nanosystem to improve cancer therapy.

Folate receptors (FRs) have been identified as cellular surface markers for cancer and leukemia. Liposomes containing lipophilic derivatives of folate have been shown to effectively target FR-expressing cells. Here, we report the synthesis of a novel lipophilic folate derivative, folate-polyethylene glycol-cholesterol hemisuccinate (F-PEG-CHEMS), and its evaluation as a targeting ligand for liposomal doxorubicin (L-DOX) in FR-expressing cells. Liposomes containing F-PEG-CHEMS, with a mean diameter of 120+/-20 nm, were synthesized by polycarbonate membrane extrusion and were shown to have excellent colloidal stability. The liposomes were taken up selectively by KB cells, which overexpress FR-alpha. Compared to folate-PEG-cholesterol (F-PEG-Chol), which contains a carbamate linkage, F-PEG-CHEMS better retained its FR-targeting activity during prolonged storage. In addition, F-PEG-CHEMS containing liposomes loaded with DOX (F-L-DOX) showed greater cytotoxicity (IC(50)=10.0muM) than non-targeted control L-DOX (IC(50)=57.5 microM) in KB cells. In ICR mice, both targeted and non-targeted liposomes exhibited long circulation properties, although F-L-DOX (t(1/2)=12.34 h) showed more rapid plasma clearance than L-DOX (t(1/2)=17.10h). These results suggest that F-PEG-CHEMS is effective as a novel ligand for the synthesis of FR-targeted liposomes.