Hyaluronic Acid-Modified Cisplatin-Encapsulated Poly(Lactic-co-Glycolic Acid) Magnetic Nanoparticles for Dual-Targeted NIR-Responsive Chemo-Photothermal Combination Cancer Therapy

Abstract

Combination chemo-photothermal therapy with nanomaterials can reduce the dose of chemotherapeutic drugs required for effective cancer treatment by minimizing toxic side effects while improving survival times. Toward this end, we prepare hyaluronic acid (HA)-modified poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (MNP) for the CD44 receptor-mediated and magnetic field-guided dual-targeted delivery of cisplatin (CDDP). By co-encapsulating the CDDP and oleic acid-coated iron oxide MNP (IOMNP) in PLGA, the PMNPc was first prepared in a single emulsification/solvent evaporation step and successively surface modified with chitosan and HA to prepare the HA/PMNPc. Spherical HA/PMNPc nanoparticles of ~300 nm diameter can be prepared with 18 and 10% (w/w) loading content of CDDP and IOMNP and a pH-sensitive drug release to facilitate the endosomal release of the CDDP after intracellular uptake. This leads to the higher cytotoxicity of the HA/PMNPc toward the U87 glioblastoma cells than free CDDP with reduced IC50, a higher cell apoptosis rate, and the enhanced expression of cell apoptosis marker proteins. Furthermore, the nanoparticles show the hyperthermia effect toward U87 after short-term near-infrared (NIR) light exposure, which can further elevate the cell apoptosis/necrosis rate and upregulate the HSP70 protein expression due to the photothermal effects. The combined cancer therapeutic efficacy was studied in vivo using subcutaneously implanted U87 cells in nude mice. By using dual-targeted chemo-photothermal combination cancer therapy, the intravenously injected HA/PMNPc under magnetic field guidance and followed by NIR laser irradiation was demonstrated to be the most effective treatment modality by inhibiting the tumor growth and prolonging the survival time of the tumor-bearing nude mice.

An Overview of Nanotherapeutic Drug Delivery Options for the Management of Glioblastoma

“…Addition of near-infrared radiation on top of magnetic targeting shortly after tail vein injection of the nanoparticles resulted in a prolonged median survival of 42 days compared to 32 days for the control group, 35 days for the nanoparticle injection only as well as the cisplatin only groups, and 39 days for nanoparticle injection with magnetic targeting only. Overall, the addition of a magnetic field with near-infrared radiation resulted in the best treatment outcomes with regard to survival and tumor burden [125].…”

“…Magnetic nanoparticles are an ever-expanding utility within the biomedical field, finding uses as contrast agents for imaging and drug delivery vehicles and even uses for hyperthermic treatments [125]. The most commonly used magnetic nanoparticles are iron oxide magnetic nanoparticles (IOMNPs) which generally consist of a biocompatible material surrounded by an iron oxide core [126].…”

Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment

“…The study groups include the following: 1, PBS (control); 2, CPT-11 + shRNA (7.5 mg/kg CPT-11 and 2.5 mg/kg shRNA); 3, TCMLs; 4, TCML@CPT-11/shRNA (7.5 mg/kg CPT-11 and 2.5 mg/kg shRNA); and 5, TCML@CPT-11/shRNA (7.5 mg/kg CPT-11 and 2.5 mg/kg shRNA) + AMF treatment (20 mT for 5 min). In each group, magnetic guidance was created by placing a magnet (2400 Gauss) around the implanted tumor site for 30 min [39]. After administration, the tumor size and body weight were recorded continuously for four weeks.…”

Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives

“…According to literatures, [342][343][344][345] NPs with active targeting possess obvious advantages: (1) the cargo has higher delivery efficiency due to the protection and shielding of DDS; (2) the NPs are more likely to avoid the clearance of the reticuloendothelial system and prolong the blood circulation time; (3) modification by targeting ligands can endow DDS with active targeting performance and improve drug utilization; (4) construction of drug controlled release mechanism can realize precise drug release of DDS in cells. In order to construct a drug delivery system with targeting function, the researchers m researchers modified cell membrane-targeting ligands on the surface of nanocarriers, mainly including folic acid, 346 hyaluronic acid, 347,348 aptamers, 349 peptides, 350,351 etc., which actively deliver cargo to specific cells through ligandreceptor specific binding.…”