Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.
MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed.
pH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug delivery systems for cancer therapy. In the present study, hepatitis B virus (HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via nitrilotriacetic acid (NTA) conjugation. The His-tags served as pH-responsive nanojoints which released DOX from VLNPs in a controlled manner. The His-tagged VLNPs conjugated non-covalently with NTA-DOX, and cross-linked with folic acid (FA) were able to specifically target and deliver the DOX into ovarian cancer cells via folate receptor (FR)-mediated endocytosis. The cytotoxicity and cellular uptake results revealed that the His-tagged VLNPs significantly increased the accumulation of DOX in the ovarian cancer cells and enhanced the uptake of DOX, which improved anti-tumour effects. This study demonstrated that NTA-DOX can be easily displayed on His-tagged VLNPs by a simple Add-and-Display step with high coupling efficiency and the drug was only released at low pH in a controlled manner. This approach facilitates specific attachment of any drug molecule on His-tagged VLNPs at the very mild conditions without changing the biological structure and native conformation of the VLNPs.
Medium-and-Long Chain Triacylglycerol (MLCT) is a type of structured lipid that is made up of medium chain, MCFA (C8-C12) and long chain, LCFA (C16-C22) fatty acid. Studies claimed that consumption of MLCT has the potential in reducing visceral fat accumulation as compared to long chain triacylglycerol, LCT. This is mainly attributed to the rapid metabolism of MCFA as compared to LCFA. Our study was designed to compare the anti-obesity effects of a enzymatically interesterified MLCT (E-MLCT) with physical blend of palm kernel and palm oil (B-PKOPO) having similar fatty acid composition and a commercial MLCT (C-MLCT) made of rapeseed/soybean oil on Diet Induced Obesity (DIO) C57BL/6J mice for a period of four months in low fat, LF (7%) and high fat, HF (30%) diet. The main aim was to determine if the anti-obesity effect of MLCT was contributed solely by its triacylglycerol structure alone or its fatty acid composition or both. Out of the three types of MLCT, mice fed with Low Fat, LF (7%) E-MLCT had significantly (P<0.05) lower body weight gain (by ~30%), body fat accumulation (by ~37%) and hormone leptin level as compared to both the LF B-PKOPO and LF C-MLCT. Histological examination further revealed that dietary intake of E-MLCT inhibited hepatic lipid accumulation. Besides, analysis of serum profile also demonstrated that consumption of E-MLCT was better in regulating blood glucose compared to B-PKOPO and C-MLCT. Nevertheless, both B-PKO-PO and E-MLCT which contained higher level of myristic acid was found to be hypercholesterolemic compared to C-MLCT. In summary, our finding showed that triacylglycerol structure, fatty acid composition and fat dosage play a pivotal role in regulating visceral fat accumulation. Consumption of E-MLCT in low fat diet led to a significantly lesser body fat accumulation. It was postulated that the MLM/MLL/LMM/MML/LLM types of triacylglycerol and C8-C12 medium chain fatty acids were the main factors that contributed to the visceral fat suppressing effect of MLCT. Despite being able to reduce body fat, the so called healthful functional oil E-MLCT when taken in high amount do resulted in fat accumulation. In summary, E-MLCT when taken in moderation can be used to manage obesity issue. However, consumption of E-MLCT may lead to higher total cholesterol and LDL level.