Dual Active Targeting Research Articles

Comparison Direct Synthesis of Hyaluronic Acid-Based Carbon Nanodots as Dual Active Targeting and Imaging of HeLa Cancer Cells.

The present study explores the potential of carbon nanodots (CDs) synthesized from hyaluronic acid using microwave-assisted and furnace-assisted methods as bioimaging agents for cancer cells. The investigation on the effect of microwave-assisted and furnace-assisted times (2 min and 2 h) on determining CD character is dominantly discussed. Various CDs, such as HA-P1 and HA-P2 were, respectively, synthesized through the furnace-assisted method at 270 °C for 2 min and 2 h, whereas HA-M1 and HA-M2 were synthesized with the microwave-assisted method for 2 min and 2 h, respectively. Overall, various CDs were produced with an average diameter, with the maximum absorption of HA-P1, HA-P2, HA-M1, and HA-M2 at 234, 238, 221, and 217 nm, respectively. The photoluminescence spectra of these CDs showed particular emissions at 320 nm and excitation wavelengths from 340 to 400 nm. Several characterizations such as X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy reveal the CD properties such as amorphous structures, existence of D bands and G bands, and hydrophilic property supported with hydroxyl and carboxyl groups. The quantum yields of HA-M1, HA-M2, HA-P1, and HA-P2 were 12, 7, 9, and 23%, respectively. The cytotoxicity and in vitro activity were verified by a cell counting kit-8 assay and confocal laser scanning microscopy, which show a low toxicity with the percentage of living cells above 80%.

Environmentally Responsive Dual-Targeting Nanoparticles: Improving Drug Accumulation in Cancer Cells as a Way of Preventing Anticancer Drug Efflux

Drug targeting and stimuli-responsive drug release are 2 active areas of cancer research and hold tremendous potential in the management of cancer drug resistance. In this study, I addressed this issue and focused on the synthesis and characterization of pH-responsive Fe3O4@SiO2(FITC)-BTN/folic acid/DOX multifunctional nanoparticles aiming to increase drug accumulation in malignancies with both dual active targeting and endosomal drug release properties. Dye-doped silica magnetic-fluorescent composite was constructed by a simple coprecipitation of Fe+2/Fe+3 salts followed by sol-gel formation and dual-targeting function was obtained by conjugating folate and biotin moieties on the silica surface of nanoparticles via an esterification reaction. Doxorubicin was then successfully attached on the amine-functionalized nanoparticles using a pH-sensitive Schiff-base formation. The physicochemical characterization of the structure was performed by dynamic light scattering, zeta potential measurement, X-ray diffraction, Fourier transform infrared spectroscopy, electron microscopy techniques, and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated an enhanced intracellular delivery and reduction of cancer cell viability in the cervical carcinoma HeLa cell line. Furthermore, proapoptotic studies showed that the nanoparticles increased the apoptotic rates within the same cancer cells. The preliminary cell tests confirm the potential of these multifunctional nanoparticles against the development of drug resistance in cancer cells.

Further Evolution of Multifunctional Niosomes Based on Pluronic Surfactant: Dual Active Targeting and Drug Combination Properties.

The loading of chemotherapics into smart nanocarriers that simultaneously possess more than one useful property for specifically targeting a tumor site improves their therapeutic effectiveness, reducing their side effects. Hence, we proposed a combined approach for the treatment of human breast cancer (BC) consisting of the co-encapsulation of doxorubicin and curcumin or doxorubicin and quercetin into multifunctional niosomes, which results in prolonged blood circulation and an ability to spontaneously accumulate at the tumor site (passive target) and to recognize and bind the tumor cells through dual ligand-receptor interactions (active target). The drug-loaded vesicles showed high stability and good capability of loading doxorubicin and antioxidants alone or in combination. Their diameter was around 400 nm. The drugs released from the vesicles were found to be controlled and sustained for over 24 h, with a strong dependence on the co-presence of the loaded molecules. Transferrin and/or folic acid were conjugated on the external surface of the niosomes as ligands, considerably improving the cellular uptake into MCF-7 and MDA-MB-231 malignant cells when compared with the uptake of nonconjugated samples. In vitro evaluation of anticancer activity demonstrated the strong potential of niosomes loaded with a doxorubicin/curcumin combination as useful devices in breast tumor treatment. These features hold great promise for the development of multifunctional devices that combine several advantages such as biocompatibility, stealth properties, loading capability, and active targeting, moving toward the development of more specific and efficient carriers for personalized tumoral therapy.

Anti-tumor activity of paclitaxel through dual-targeting lipoprotein-mimicking nanocarrier

In the present study, we devised a strategy that paclitaxel (PTX) with lipid and octadecylamine were prepared to lipid nanoparticle (PTX-LNP) with positive charge, folic acid-modified bovine serum albumin (FB)-coated surface of PTX-LNP through electrostatic attraction and generated the lipoprotein-mimicking nanocomplex (FB-PTX-LNP) for dual-targeting therapy. Bovine serum albumin (BSA) was used as the protein model due to its specific targeting to tumor by increased transendothelial gp60-mediated transport and increased intratumoral accumulation as a result of the secreted protein, acidic and rich in cysteine (SPARC)–albumin interaction. The further conjugating folic acid to BSA achieved the dual active targeting. In vitro cytotoxicity tests suggested FB-PTX-LNP and BSA-PTX-LNP exhibited significantly higher cytotoxic activity against MCF-7 and HepG2 cells compared to PTX-LNP. The cellular uptake experiments indicated that FB-coumarin-6-LNP modified with dual-targeting had a faster and greater cellular uptake when compared to BSA-coumarin-6-LNP and coumarin-6-LNP by MCF-7 cells. Thus, both BSA and FA did play roles in in vitro cytotoxicity and cellular uptake. Furthermore, the targeting ability and therapeutic efficacy of FB-PTX-LNP were assessed in vivo. FB-PTX-LNP produced very marked targeting ability and anti-tumor activity in MDA-MB-231 tumor-bearing mice. These results indicate the protein–lipid nanocomplex FB-PTX-LNP is a potential nanocarrier for Paclitaxel dual-targeting to tumor.