Dual agent loaded PLGA nanoparticles enhanced antitumor activity in a multidrug-resistant breast tumor eenograft model.

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic.

Gene Therapy and Photothermal Therapy of Layer-by-Layer Assembled AuNCs /PEI/miRNA/ HA Nanocomplexes.

BACKGROUND: MicroRNA (miRNA) therapy, which was widely considered to treat a series of cancer, has been confronted with numerous obstacles to being delivered into target cells because of its easy biodegradation and instability. METHODS: In this research, we successfully constructed 11-mercaptoundecanoic acid modified gold nanocages (AuNCs)/polyethyleneimine (PEI)/miRNA/hyaluronic acid (HA) complexes (abbreviated as AuNCs/PEI/miRNA/HA) using a layer-by-layer method for target-specific intracellular delivery of miRNA by HA receptor mediated endocytosis. RESULTS: The results of UV spectra, hydrodynamic diameter and zeta potential analyses confirmed the formation of AuNCs/PEI/ miRNA/HA complex with its average particle size of ca. 153 nm and surface charge of ca. -9.43 mV. Next, we evaluated the antitumor effect of the nanocomplex mediated by the combination of gene therapy and photothermal therapy (PTT) against hepatocellular carcinoma (HCC) in vitro. CONCLUSION: Our experimental results indicated that the AuNCs/PEI/miRNA/HA complex effectively delivered miRNA to the target cells and its antitumor effect was significantly enhanced by the combination of gene therapy and photothermal therapy. In addition, anti-miR-181b could promote Bel-7402 cell arrest in S phase and improve TIMP-3 mRNA expression. All these results suggested that AuNCs/PEI/miRNA/HA gene delivery system with combination of gene therapy and photothermal therapy might be exploited for HCC treatment.

[Rat dental papilla cell culture with nanometer-HAP in vitro].

OBJECTIVE: To determine the effects of nano-hydroxyapatite(nano-HAP)on the proliferation and activity of rat dental papilla cells(RDPCs)in vitro, and to evaluate the feasibility of using nano-hydroxyapatite(nano-HAP)as dental papilla cell scaffold in dental tissue engineering. METHODS: RDPCs cultured with the porous nano-HAP in vitro served as the experimental group, and the routine culture of RDPCs in flasks served as the control. Scanning electronic microscope was used to observe the growth and adherence of the RDPCs to nano-HAP. Cell proliferation, cellular protein content, and alkaline phosphatase(ALP) were detected to assess the cellular activities. RESULTS: RDPCs proliferated well, and adhered to the outer and inner surface of the nano-HAP scaffold. Compared with the control group, cells in the experimental group presented higher proliferation on 6 d and 8 d and higher cellular protein content on 6 d and 9 d. No significant difference was detected in the ALP activity in the 2 groups. CONCLUSION: RDPCs seeded into nano-HAP grow better and have more vigorous cellular activity, suggesting that nano-HAP has excellent biocompatibility with dental papilla cells, and it can serve as a promising scaffold for dental tissue engineering.

[Construction of tissue engineered gingiva with gingival epithelia and acellular dermal matrix].

OBJECTIVE: To culture human gingival epithelia in vitro, and to construct the tissue engineered gingiva with the acellular dermal matrix (ADM). METHODS: Human gingival epithelia were isolated from the gingival tissue, and the cells were cultured and seeded onto the surface of ADM. After 7 days of submerged incubation, an air-liquid interface culture was performed for 7, 14, and 21 days. The complex constructed above was taken for histological examination. RESULTS: Human gingival epithelia could proliferate well on the surface of ADM, and form multilayer structure. But the superficial epithelium was partially keratinized. CONCLUSION: Tissue engineered gingiva may be constructed with human gingival epithelia and ADM in vitro.