Poly(aspartic acid)-based Degradable Assemblies for Highly Efficient Gene Delivery

Abstract

Due to its good properties such as low cytotoxicity, degradability, and biocompatibility, poly(aspartic acid) (PAsp) is a good candidate for the development of new drug delivery systems. In this work, a series of new PAsp-based degradable supramolecular assemblies were prepared for effective gene therapy via the host-guest interactions between the cyclodextrin (CD)-cored PAsp-based polycations and the pendant benzene group-containing PAsp backbones. Such supramolecular assemblies exhibited good degradability, enhanced pDNA condensation ability, and low cytotoxicity. More importantly, the gene transfection efficiencies of supramolecular assemblies were much higher than those of CD-cored PAsp-based counterparts at various N/P ratios. In addition, the effective antitumor ability of assemblies was demonstrated with a suicide gene therapy system. The present study would provide a new means to produce degradable supramolecular drug delivery systems.

Covalent nano delivery systems for selective imaging and treatment of brain tumors

“…(2) Poly(aspartic acid) segments have been shown to bind to hydroxyapatite (HA) and could be applied for the targeting of nanoparticles to bone tissue [77]. (3) Because of its biocompatibility including biodegradability and negligible immunogenicity, the potency of PAA to form different covalent combinations with polycations and cyclodextrin to form nucleic acid complexes for gene delivery have been recognized and developed into biodegradable nucleic acid delivery assemblies [78, 79]. In these studies, PAA was employed as the platform for covalent attachment of several kinds of nucleic acid interactive molecules, such as ethylamine derivatives to form polycation-like structures, benzyl alcohol esterification of pendant carboxyl groups to introduce hydrophobicity, and cyclodextrin for engaging host-guest nucleic acid interactions.…”

Recent progress in gene therapy to deliver nucleic acids with multivalent cationic vectors

“…(ii) multivalent cationic lipids [67,78,139,178,181], derivated oligoamines [182] and tripeptide multivalent lipids [122]; (iii) cationic polymers derivatives from PEI [124,127,183,184], PAMAM [132,140], PDMAEMA [123,133,185], PAA [103,131,186,187], chitosan [188], polyphosphoramidates [189], polyhydroxyalkanoate [92], polyamines [107], polyaminoacids [127,190] or diblock copolymers [191]; (iv) polycations from calixarene [40,136,165,192] or cyclodextrin [134,135,142,164,193] derivatives; (v) lipopolymers from lysine derivatives [170]; (vi) pendant polymercationic cyclodextrins [129,130,163]; and (vii) cationic polymer-cyclodextrin polyrotaxanes [89]. The picture that results from these transfection studies is that many of the polyplexes show efficacies comparable to that reported by the Lipo2000 positive control and also by most of the commercial or synthezised univalent CLs, but its efficacy as transfecting agents of DNA is still below than that reported by most of t...…”

“…In addition to the previous TE and KE biological studies, microscopic methods have been frequently used to visualize the level of % GFP expression inside the cells after MVCLs containing dendritic headgroups [72,121] or cyclen-based [120] lipids; (c) cationic polymers based on PEI and PAA derivatives [124,183], phospholipid-polymer [203], aminoacid-based [126,127,190], chitosan [204], PDMAEMA [133], dendrimers as PAMAM derivatives [132,201], others cationic polymer-type [107,164] or PEG-PPG-PEG/cyclodextrin polyrotaxanes [89]; and (d) polycations based on calixarenes [166,205] or cyclodextrins [106,136,142]. With respect to gene silencing/knockdown siRNA studies, micrographs and/or images have been reported for systems where the following gene vectors have been used: (a) MVCLs based on dendritic lipids [104]; and (b) cationic polymers based on dendrimers [199], diblock copolymers [105] or POEAA [144], last one in vivo studies.…”

“…22 polycation derivatives from calixarene [40,192] or cyclodextrin [106,134,142,164,193]; (v) pendant polymer-cationic cyclodextrins [129,167]; and (vi) cationic polymercyclodexdtrin polyrotaxanes [88,89,168]. These studies have reported that: a) GCLs and MVCLs offer a better cell viability than the positive controls (Lipo2000 or PEI)…”

“…For all these reasons, cryo-TEM, where the sample is fastly vitrified at very low temperature and directly deposited on the grid, is considered as the best microscopy method. AFM studies have been reported to characterize (size and shape) of complexes formed by: (a) pDNA with gemini cationic lipids[59,91,137,159,160], cationic polymers[65,124,129,130,[161][162][163][164],…”