Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructured lipid carriers（NLC）. Real--time penetration of folate--or cell penetrating peptide（CPP）-modified NLC was evaluated using a multicellular tumor spheroid（MTS） established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.
Hepatocellular carcinoma （HCC） is one of the major causes of death worldwide. Targeted delivery of drugs to tumor cells can be achieved by introduction of a targeting ligand onto the nanocarrier system. Simultaneous delivery of a chemotherapeutic drug and siRNA in one nanocarrier system to the tumor is a promising strategy for cancer treatment. In this study, we prepared cationic liposomes to co-deliver docetaxel （DTX） and small interfering RNA （siRNA）. The liposomes were modified by a hepatocellular carcinoma specific homing peptide, SP94. Serum stability assay demonstrated that liposomes can significantly protect the siRNA against enzymatic degradation in serum. The SP94 modified liposomes showed increased cellular uptake and stronger anti-tumor effect compared with the unmodified liposomes on human HCC cells. The data indicated that the SP94 modified liposomes which co-deliver DTX and siRNA could be used for the targeted therapy of hepatocellular carcinoma.
The epidemiological statistics reveals the striking patterns of cancer in women and highlights the need for novel therapeutic strategies. In this work, mesoporous silica nanoparticles（MSNs） as representative of inorganic nanoparticles were prepared for loading si RNA that plays a role of gene silencing to treat breast carcinoma（MCF-7） cells. The critical processes of synthesis were optimized for the nanoparticles with desired quality attributes that have the enlarged pores for elevated loading capacity. After si RNA loading into mesoporous, crosslinked-polyethylenimine was employed as the cap to coat the enlarged MSN pores and protect the cargo from leakage. The elevated quantity of si RNA（35 μg si RNA/mg MSNs） were loaded in the MSNs. The as-synthesized MSNs were further evaluated on MCF-7 cells in vitro and shown negligible cytotoxicity. As expected, the si RNA loaded in the as-synthesized MSNs was readily internalized into MCF-7 cells and displayed 420 times higher intake than that of naked si RNA. The MSNs may be exploited to become an effective si RNA cell delivery strategy and further studied for the anti-tumor efficacy.
Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanoparticles have been reported, but the underlying mechanism remains largely unknown. In our study, we aim to understand the safety of paclitaxel （PTX） loaded bovine albumin nanoparticles （BNPs） and active targeted PTX loaded BNPs to normal vital organ or tissue in vivo. The anti-human epidermal growth factor receptor 2 （HER2/neu） peptide mimetic （AHNP） was covalent bound to surface of BNPs （AHNP-BNPs） to exert selected delivery to HER2＋ cells. In HER2＋ tumor xenographs, saline （control）, PTX traditional formula （medium of Cremophor EL-ethanol）, BNPs, and AHNP-BNPs were administrated to evaluate the toxicity. There is no severe neutropenia or anemia with treatment of BNPs and AHNP-BNPs compared with traditional PTX injection. We also evaluated their damage on normal organs, including liver, kidney, spleen, lung and heart to fully estimate the safety of AHNP-BNPs and BNPs delivery systems. We observed similar toxicity in liver and lung in mice treated with BNPs or PTX injection, but decreased liver damage in mice treated with AHNP-BNPs. Further studies are rcouired to confirm our conclusion.
Drug delivery by nanocarriers requires characterizations of suitable particle size, high drug loading and safety. In this work, we prepared an amphiphilic dendrimer modified PEG-PLA mixed nanoparticles（NPs） by a double emulsion-solvent evaporation（DESE） method. The particle size and drug encapsulation efficacy（EE） were compared to evaluate and optimize the preparation parameters. The mixed NPs had average size ranging from（102±1） nm to（137±5） nm, and the zeta potential turned to positive with incorporation of the amphiphilic dendrimer. The NPs showed different EE of docetaxel（DTX） and paclitaxel（PTX） with higher affinity to more lipophilic PTX. The blank mixed NPs showed little cytotoxicity, and the DTX-loaded NPs could effectively facilitate the antiproliferation activity on PC-3 cells. The NPs could be used as an effective drug delivery system, and its anti-tumor effect is worthy of further study.
It is a promising treatment strategy to use a nanoparticle-based drug delivery system for cancer patients, which can simultaneously deliver multiple drugs or genes in combination with therapy to induce synergistic effects and suppress drug resistance to the tumor. In this study, cationic nanostructured lipid carriers（cNLC） for co-loading anionic small-interfering RNAs（siRNA） and chemotherapeutic docetaxel（DTX） were prepared from different cationic lipids based on particle distribution and loading efficiency. In order to increase the cNLC＇s positive targeting capacity, a novel peptide SP94 was bound to the surface of cNLC（SP94-cNLC）. The cNLC showed good efficiency in loading siRNA and DTX. The SP94-cNLC revealed a better cytotoxicity compared with cNLC and Taxotere？, indicating that SP94 could successfully enhance the internalization capacity of nanoparticles to the liver cancer cells. This new type of cNLC is a potential vehicle when using in co-delivery of chemotherapeutics and siRNAs. The curcumin（CUR）/DTX co-delivery NLC could load both CUR and DTX in high efficiency and showed a sensibilization to DTX chemotherapy. The sensibilization was more obvious when it was used in the aggressive and resistant cancer cells. This CUR/DTX co-delivery system had good potential in treating cancer cells when chemotherapy drug showed little effect alone.
