Thiophene Derivatives as Anticancer Agents and Their Delivery to Tumor Cells Using Albumin Nanoparticles

Abstract

A series of thiophene derivatives (TPs) were synthesized and evaluated for cytotoxicity in HepG2 and SMMC-7721 cell lines by MTT assay. TP 5 was identified as a potential anticancer agent based on its ability to inhibit tumor cell growth. Drawbacks of TPs, including poor solubility and high toxicity, were overcome through delivery using self-assembling HSA nanoparticles (NPs). The optimum conditions for TP 5-NPs synthesis obtained by adjusting the temperature and concentration of TP 5. The NPs had an encapsulation efficiency of 99.59% and drug-loading capacity of 3.70%. TP 5 was slowly released from TP 5-NPs in vitro over 120 h. HepG2 and SMMC-7721 cell lines were employed to study cytotoxicity of TP 5-NPs, which exhibited high potency. ROS levels were elevated and mitochondrial membrane potentials reversed when the two cell lines were treated with TP 5-NPs for 12 h. Cellular uptake of fluorescence-labeled TP 5-NPs in vitro was analyzed by flow cytometry and laser confocal scanning microscopy. Fluorescence intensity increased over time, suggesting that TP 5-NPs were efficiently taken up by tumor cells. In conclusion, TP 5-NPs showed great promise as an anticancer therapeutic agent.

Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma

“…It was noticeable that the averaged particle size of Tf-LPs was ~90 nm by TEM, which was smaller than the average size determined by DLS (128.64 nm). This was because DLS showed Tf-LPs in the hydrated state, while TEM displayed particles in the dried state [8]. Both Tf and R8 could improve the cellular uptake of Tf-LPs [11,19].…”

“…However, the uptake fluorescence intensity of Tf-LPs was similar to that of TPs, this is because the TfR in the normal cells surface is low expressed and because of the absence of the tumor-targeting effect. The only barrier for drug release is the diffusion of the drug from one side to the other of the dialysis membrane in free DOX, whereas, for LPs or Tf-LPs, there are roughly 2 stages: the release of the drug from NPs and then diffusion through the membrane [4,8]. Therefore, the drug release of Tf-LPs presented a slow release rate.…”

“…For cytotoxicity of Tf-LPs, free DOX showed a higher inhibition rate than LPs at 48 h, the main reason is that free DOX could be quickly transported into cells by passive diffusion under in vitro conditions. However, LPs prevents drug access to tumor cells due to slow-release [4,8,20,21,25]. Due to the existence of Tf, Tf-LPs possessed stronger anti-proliferation than free DOX, indicating that Tf promoted cellular uptake for DOX and increased the antitumor effect.…”

“…Nanovehicles represented an attractive strategy for the delivery of chemotherapeutic agents in glioma [8,9]. An ideal nanovehicle for the treatment of glioma should be able to cross the BBB and target tumor cells [10].…”

“…In the past few years, various nanocarriers, including polymers and liposomes, had been developed. Liposomes are considered “self” by the immune system and possess many advantages such as good biocompatibility, low toxicity, and non-immunogenicity [11], however, delivery of liposomes across the BBB remains a great challenge [8,9].…”