Star-Shaped Amphiphilic Hyperbranched Polyglycerol Conjugated with Dendritic Poly(l-lysine) for the Codelivery of Docetaxel and MMP-9 siRNA in Cancer Therapy

Abstract

The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.

Nano‐Star‐Shaped Polymers for Drug Delivery Applications

“…[28,29] It is especially useful in delivering hydrophobic drugs in aqueous environments. [30] www.advancedsciencenews.com www.mrc-journal.de formation, allowing greater control over the exact arm structure required, ideal for synthesizing miktoarm stars. This method also avoids the complication of low molecular weight cores that is further explained in the "core-first" approach later.…”

“…Star‐shaped polymers, with their functionalizable branch arms can be chemically modified to control the biodegradation rates inside the body, incorporated stimuli‐responsive moieties to allow spatial and temporal control for drug delivery, or synthesized with specific biomarkers to target the delivery of these star‐shaped drug delivery polymers to the desired physiological environments such as cancer cells . It is especially useful in delivering hydrophobic drugs in aqueous environments …”

Biodegradable Gene Carriers Containing Rigid Aromatic Linkage with Enhanced DNA Binding and Cell Uptake

“…Compared to viral vectors, cationic polymers exhibit several advantages including inherent low immunogenicity, convenient production, as well as tunable surface and structure [7,8,9]. Various of polycation carriers like poly- l -lysine (PLL), polyethylenimine (PEI), poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA), and polyamidoamine (PAMAM) dendrimers have been explored [8,10,11,12]. However, the high cytotoxicity came from their polycationic characters and relatively low transfection efficiency when compared to viral vectors largely limited their clinical application.…”

Synthesis and functionalization of hyperbranched polymers for targeted drug delivery

“…Like dendrimers, HBPs form cavities that can be used to encapsulate cargos of different sizes [118] including small chemotherapeutic drugs such as DOX, [119,120] camptothecin (CPT), [121,122] cisplatin, [123][124][125] [127][128][129][130] and siRNA [131][132][133] form complexes with unimolecular HBPs such as branched poly(ethylene imine) (PEI) [134] by electrostatic interactions. Tuning the structure of HBPs permits to control the strength of the interaction between gene and carrier by modulating the charge density at its surface, adjusting its molecular weight, and preparing different molecular structures.…”