Multifunctional particles for melanoma-targeted drug delivery

Abstract

New magnetic-based core-shell particles (MBCSP) were developed to target skin cancer cells while delivering chemotherapeutic drugs in a controlled fashion. MBCSP consist of a thermo-responsive shell of poly(N-isopropylacrylamide-acrylamide-allylamine) and a core of poly(lactic-co-glycolic acid) (PLGA) embedded with magnetite nanoparticles. To target melanoma cancer cells, MBCSP were conjugated with Gly-Arg-Gly-Asp-Ser (GRGDS) peptides that specifically bind to the α5β3+ receptor of melanoma cell. MBCSP consist of unique multifunctional and controlled drug delivery characteristics. Specially, they can provide dual drug release mechanisms (a sustained release of drugs through degradation of PLGA core and a controlled release in response to changes in temperature via thermo-responsive polymer shell), and dual targeting mechanisms (magnetic localization and receptor-mediated targeting). Results from in vitro studies indicate that GRGDS-conjugated MBCSP has an average diameter of 296 nm and exhibit no cytotoxicity towards human dermal fibroblasts up to 500 μg ml−1. Further, a sustained release of curcumin from the core and a temperature-dependent release of doxorubicin from the shell of MBCSP were observed. The particles also produced a dark contrast signal in magnetic resonance imaging. Finally, the particles were accumulated at the tumor site in a B16F10 melanoma orthotopic mouse model, especially in presence of a magnet. Results indicate great potential of MBCSP as a platform technology to target, treat, and monitor melanoma for targeted drug delivery to reduce side effects of chemotherapeutic reagents.

Curcumin loaded PLGA–poloxamer blend nanoparticles induce cell cycle arrest in mesothelioma cells

“…Moreover, CD-CURC 78 complexation enhances CURC anti-inflammatory and antiprolifera-79 tive effect and also led to a promoted delivery to specific cancer 80 cell populations [11,12]. CURC encapsulation in biodegradable 81 nanoparticles (NPs), based on poly(lactic-co-glycolic acid) (PLGA), 82 allows to increase its circulation times/half life, cell permeability 83 and resistance to metabolic degradation, and also promotes con- 84 trolled release and targeting [13][14][15][16][17]. It must be underlined that 85 size, surface charge and hydrophilicity of NPs in which the drug http …”

Development and Characterization of Stimulus-Sensitive Nano/Microparticles for Medical Applications

“…Our lab has previously synthesized multilayered NPs consisting of iron oxideembedded polylactic-co-glycolic acid (PLGA) polymer core and PNIPAM-based shell for dual-drug release to treat melanoma. DOX was encapsulated in the shell made of PNIPAM which was modified using acrylamide (AAm) and allylamine (AH) to increase the LCST to 41 C [19]. An alternating magnetic field could be used to produce heat in the iron oxide particles at the site of interest so that LCST can be achieved.…”

Optical tweezers based measurement of PLGA-NP interaction with prostate cancer cells

“…The PLGA-NPs were synthesized using a standard single (oil-in-water, o/w) emulsion technique, as previously described [14][15][16]. Briefly, the oil/organic phase consisting of PLGA (Lakeshore Biomaterials, Birmingham, AL), bare iron oxide nanoparticles (Meliorum technologies, Rochester, NY) and coumarin-6 was prepared in dichloromethane (DCM) and sonicated at 20W for 8 minutes.…”

“…The nanoparticles were then washed and collected via ultracentrifugation and lyophilization [14]. For the conjugation of targeting ligands such as Folic acid and R11on the surface of the nanoparticles, carbodiimide chemistry was implemented as described previously [16][17]. The NP solution was ultrasonicated and sufficiently diluted (10 ng/ml) so that only few NPs were present in the petridish containing prostate cancer cells.…”