A nanoparticle formula for delivering siRNA or miRNAs to tumor cells in cell culture and in vivo

Abstract

To improve RNA delivery, we present a protocol to produce an RNA carrier based on a Zn(II)-dipicolylamine (Zn-DPA) analog, which is an artificial receptor for phosphate anion derivatives. We further functionalized this Zn-DPA analog to hyaluronic acid (HA)-based self-assembled nanoparticles (HA-NPS) with a hydrodynamic diameter of 100 nm by conjugating amine-functionalized Zn-DPA molecules onto the HA-NPS through amide formation, resulting in efficient tumor-targeted delivery of RNAs (siRNAs, miRNA or other short oligoribonucleotides) and small-molecule drugs. The functional group of Zn-DPA can be converted into other groups such as a carboxylic or thiol group, and the DPA analog can be covalently attached to a variety of existing and novel platforms or formulations for the development of multifunctional materials via standard bioconjugation techniques. protocols for RNA formulation and delivery into tumor tissues and tumor cells are also described. our design strategy offers a versatile and practical method for delivering both RNA and chemotherapeutics to tumor cells and expands existing nanomaterial capabilities to further the field of drug and gene delivery.

Preparation and Characterization of Hyaluronic Acid-Polycaprolactone Copolymer Micelles for the Drug Delivery of Radioactive Iodine-131 Labeled Lipiodol

“…After the 12-hour dialysis, 131 I-lipiodol loaded micelles were formed and suspended in ultrapure water. The protocol for lipophilic molecules was conducted according to standard procedures [27]. …”

Imaging and therapeutic applications of zinc(ii)-dipicolylamine molecular probes for anionic biomembranes

“…129 ZnDPA complexes were covalently conjugated to hyaluronic acid-based nanoparticles to enable efficient tumor-targeted delivery of RNAs and small-molecule drugs. 130 ZnDPA-coated nanoparticles were loaded with siRNA specific for a bioluminescence gene within cancer cells were and tested in a mouse colon cancer model. Bioluminescent intensities from tumors treated with RNA-delivering nanoparticles showed a substantial decrease in signal 24 h after injection, demonstrating substantial promise for drug delivery.…”

A novel paclitaxel-loaded poly(D,L-lactide-co-glycolide)-Tween 80 copolymer nanoparticle overcoming multidrug resistance for lung cancer treatment

“…However, it seems that single drugloaded NPs demonstrated some kind of efficacy against tumor growth inhibition but not so efficient. 21 It may be attributed to the tumor heterogeneity, complexity of drug resistance, and barriers of NPs circulating and crossing in vivo. 19,29,30 There are already substantial efforts to incorporate multiple functionalities and moieties within the nanoparticle design.…”

“…Apart from the application in cancer diagnosis, there has been a great interest in developing new nanomaterials for cancer treatment. 20,21 Poly (d,l-lactide-co-glycolide) (PLGA), a biodegradable and biocompatible synthetic polymer approved by the US Food and Drug Administration, is widely used in drug delivery system. [22][23][24] Various studies have reported that multiple drug resistance could be overcome by PLGA NPs codelivering anticancer drug and p-gp inhibitors, indicating that PLGA NPs may be a promising approach to overcome drug resistance.…”