Hyaluronic Acid-Targeted Niosomes for Effective Breast Cancer Chemostarvation Therapy.

Chemotherapy is widely used for cancer therapy; however, its efficacy is limited due to poor targeting specificity and severe side effects. Currently, the next generations of delivery systems with multitasking potential have attracted significant attention for cancer therapy. This study reports on the design and synthesis of a multifunctional nanoplatform based on niosomes (NIO) coloaded with paclitaxel (PTX), a chemotherapeutic drug commonly used to treat breast cancer, and sodium oxamate (SO), a glycolytic inhibitor to enhance the cytotoxicity of anticancer drug, along with quantum dots (QD) as bioimaging agents, and hyaluronic acid (HA) coating for active targeting. HN@QPS nanoparticles with a size of ∼150 nm and a surface charge of -39.9 mV with more than 90% EE for PTX were synthesized. Codelivery of SO with PTX remarkably boosted the anticancer effects of PTX, achieving IC50 values of 1-5 and >0.5 ppm for HN@QP and HN@QPS, respectively. Further, HN@QPS treatment enhanced the apoptosis rate by more than 70% in MCF-7 breast cancer cells without significant cytotoxicity on HHF-2 normal cells. Also, quantification of mitochondrial fluorescence showed efficient toxicity against MCF-7 cells. Moreover, the cellular uptake evaluation demonstrated an improved uptake of HN@Q in MCF-7 cells. Taken together, this preliminary research indicated the potential of HN@QPS as an efficient targeted-dual drug delivery nanotheranostic against breast cancer cells.

MUC-1 aptamer conjugated InP/ZnS quantum dots/nanohydrogel fluorescent composite for mitochondria-mediated apoptosis in MCF-7 cells.

The combined use of nanohydrogels (NHGs) and quantum dots (QDs) has resulted in the development of a nanoscaled drug delivery system (DDS) with fluorescence imaging potential. NHG-QDs composite loaded with anti-cancer drugs could be applied as an effective theranostics for simultaneous diagnosis and therapy of cancer cells. Here, we report on the synthesis of NHG-QDs nanosystem (NS) conjugated with an amino-modified MUC-1 aptamer (Ap) and loaded with hydrophobic paclitaxel (PTX). To effectively target and eradicate breast cancer MCF-7 cells, the nanocomposite was further loaded with the inhibitor of lactate dehydrogenase (LDH), sodium oxamate (SO) (Ap-NHG-QDs-PTX-SO) to inhibit the conversion of pyruvate to lactate via LDH and disrupting glycolysis. Results obtained from in vitro analysis (MTT assay, apoptosis/necrosis assessment, evaluation of mitochondria targeting, and gene expression profiling) revealed that Ap-NHG-QDs-PTX-SO NS could significantly target and inhibit MCF-7 cells and also induce mitochondria-mediated apoptosis. Collectively, the Ap-NHG-QDs-PTX-SO NS is proposed to serve as a robust theranostics for simultaneous imaging and therapy of breast cancer and other types of solid tumors.

Doxorubicin-conjugated D-glucosamine- and folate- bi-functionalised InP/ZnS quantum dots for cancer cells imaging and therapy.

Nanoscaled quantum dots (QDs), with unique optical properties have been used for the development of theranostics. Here, InP/ZnS QDs were synthesised and functionalised with folate (QD-FA), D-glucosamine (QD-GA) or both (QD-FA-GA). The bi-functionalised QDs were further conjugated with doxorubicin (QD-FA-GA-DOX). Optimum Indium to fatty acid (In:MA) ratio was 1:3.5. Transmission electron microscopy (TEM) micrographs revealed spherical morphology for the QDs (11 nm). Energy-dispersive spectroscopy (EDS) spectrum confirmed the chemical composition of the QDs. MTT analysis in the OVCAR-3 cells treated with bare QDs, QD-FA, QD-GA, QD-FA-GA and QD-FA-GA-DOX (0.2 mg/mL of QDs) after 24 h indicated low toxicity for the bare QDs and functionalised QDs (about 80-90% cell viability). QD-FA-GA-DOX nanoparticles elicited toxicity in the cells. Cellular uptake of the engineered QDs were investigated in both folate receptor (FR)-positive OVCAR-3 cells and FR-negative A549 cells using fluorescence microscopy and FACS flow cytometry. The FA-functionalised QDs showed significantly higher uptake in the FR-positive OVCAR-3 cells, nonetheless the GA-functionalised QDs resulted in an indiscriminate uptake in both cell lines. In conclusion, our findings indicated that DOX-conjugated FA-armed QDs can be used as theranostics for simultaneous imaging and therapy of cancer.