Docetaxel loaded mPEG-PLA nanoparticles for sarcoma therapy: preparation, characterization, pharmacokinetics, and anti-tumor efficacy.

Sarcoma represents one of the most common malignant tumors with poor treatment outcomes and prognosis. Docetaxel (DTX) is acknowledged as one of the most important chemotherapy agents. The aim of this study was to improve the efficacy of docetaxel by incorporation into the mPEG-PLA nanoparticle (DTX NP) for the treatment of sarcoma. The DTX NP was prepared by emulsion solvent diffusion method and the prescription and preparation process were optimized through a single factor experiment. The optimized DTX NP was characterized by drug loading, encapsulation efficiency, drug release, etc. Then, the pharmacokinetics was conducted on rats and tumor-bearing ICR mice. Finally, the anti-tumor efficacy of DTX NP with different dosages was evaluated on tumor-bearing ICR mice. The optimized DTX NP was characterized by around 100 nm sphere nanoparticles, sustained in vitro drug release with no obvious burst drug release. Compared with DTX injection, the AUC of DTX NP increased by 94.7- and 35.1-fold on the rats and tumor-bearing ICR mice models, respectively. Moreover, the intra-tumoral drug concentration increased by 5.40-fold. The tumor inhibition rate of DTX NP reached 94.66%, which was 1.24 times that of DTX injection (76.11%) at the same dosage, and the bodyweight increase rate was also higher than the DTX injection. The study provided a DTX NP, which could significantly improve the bioavailability and therapeutic efficacy of DTX as well as reduced its toxicity. It possessed a certain prospect of application for sarcoma treatment.

Adjuvant cytokine-induced killer cells with minimally invasive therapies augmented therapeutic efficacy of unresectable hepatocellular carcinoma.

OBJECTIVE: To investigate the safety and therapeutic efficacy of adjuvant cytokine-induced killer (CIK) cells to minimally invasive therapies in unresectable hepatocellular carcinoma (u-HCC). MATERIALS AND METHODS: Hundred patients diagnosed with having u-HCC in our department from January 1, 2001, to July 31, 2018, were recruited. Forty-three patients received microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) together with autologous CIK cell treatment (TACE + MWA + CIK group), whereas 57 patients received TACE and MWA only (TACE + MWA group). Postprocedural complications and cumulative therapeutic effects were assessed in all patients. The disease control rate, median survival time (MST), and cumulative survival rate were compared between the cohorts using the Kaplan-Meier method and unpaired Student's t-tests. RESULTS: The overall response (complete response [CR] + partial response [PR]) rate was 74.42% (32/43) and 77.19% (44/57) for TACE + MWA + CIK and TACE + MWA groups, respectively (P = 0.243). Those of the TACE + MWA + CIK group had better rates of disease control (CR + PR + stable disease) in contrast to the TACE + MWA group (87.72% vs. 79.07%, respectively) but this failed to achieve statistical significance (P = 0.748). Based on the Kaplan-Meier survival graphs, those of the TACE + MWA + CIK groups possessed markedly increased overall survival (41 months vs. 24 months, P = 0.002) and progression-free survival (17 months vs. 10 months, P = 0.023) rates in compared to the TACE + MWA group. Survival rates were raised also TACE + MWA + CIK group than in TACE + MWA group (P = 0.002), with a MST of 6.13 ± 0.83 months and 11.61 ± 1.59 months in the TACE + MWA + CIK and TACE + MWA groups, respectively. Patients in the TACE + MWA + CIK group were not reported to have any severe complications. CONCLUSION: CIK cell immunotherapy as an adjuvant to TACE and MWA enhanced long-term prognosis and improved quality of life in patients with u-HCC. This regimen may be recommended as a novel treatment regime in u-HCC patients.