Well‐Defined Degradable Cationic Polylactide as Nanocarrier for the Delivery of siRNA to Silence Angiogenesis in Prostate Cancer

Abstract

Well-defined tertiary amine-functionalized cationic polylactides (CPLAs) are synthesized by thiol-ene click functionalization of an allyl-functionalized polylactide, and utilized here for the delivery of interleukin-8 (IL-8) siRNA via CPLA-IL-8 siRNA nanoplexes. The CPLAs possess remarkable hydrolytic degradability, and their cytotoxicity is relatively low. The CPLA-IL-8 siRNA nanoplexes can be readily taken up by prostate cancer cells, resulting in significant IL-8 gene silencing. It is found that the degradability and cytotoxicity of CPLAs, as well as the transfection efficiency of the CPLA-IL-8 siRNA nanoplexes, positively correlate with the amine mol% of CPLAs.

Poly(ethylene glycol)-block-cationic polylactide nanocomplexes of differing charge density for gene delivery

“…GPC analysis showed that their elution peak positions at 17.5e17.6 mL and PDI values of 1.06 were very close to those of precursor 2 (Fig. 3a), indicating that the side group functionalization did not considerably affect hydrodynamic volume of the polymer and that side reactions in click functionalization were successful suppressed [37]. The high degree of molecular homogeneity exhibited by PEG-b-CPLAs is beneficial for screening optimal cationic polymer:gene nanocomplex formulations because concerns of artifacts attributed to broad molecular weight distributions can be excluded.…”

“…mPEG-OH was dried as follows prior to use: mPEG-OH was dissolved in 1 mL dried DCM, followed by complete solvent removal, and the cycle was repeated five times; toluene was used as solvent to treat mPEG-OH for another five cycles. Allyl-functionalized LA monomer 1 was prepared through the method we reported previously [37]. All other chemicals were used without further purification.…”

“…Recently, we synthesized biodegradable cationic polylactides (CPLAs) through ring-opening polymerization (ROP) and thiol-ene functionalization, and further utilized them for delivery of siRNA to prostate cancer cells and pDNA to macrophage and fibroblast cells [37,38]. As compared with commercial gene delivery vectors (Fugene 6), CPLAs provided enhanced transfection efficiencies due in part to high complexation ability and degradability at physiological conditions.…”

Lipidoid Tail Structure Strongly Influences siRNA Delivery Activity

“…2,14,15,20,21 Although our group and others have come to appreciate the importance of tertiary amines within intracellular delivery materials, structure function understanding generally has been limited to the alkyl-amines that are one of the two precursors to lipidoids. 5,21,28,29 The structural importance of the second precursor, the alkyl tail, has not yet been thoroughly investigated.…”

Shell Cleavable Dendritic Polyglycerol Sulfates Show High Anti‐Inflammatory Properties by Inhibiting L‐Selectin Binding and Complement Activation

“…dPG-pentenoate ( 8 ) was obtained in 92% yield with a dF = 84%, as determined by 1 H-NMR. Subsequent radical thiol-ene reaction of 8 with thioglycerol was performed under UV-radiation for 90 min at room temperature with 2,2-dimethoxy-2-phenylacetophenone (DMPA) as the photoinitiator following a modifi ed procedure from Chen et al [ 26 ] dPG-thioglyceryl pentanoate (dPG-TP, 9 ) was obtained in 77% yield with complete conversion as determined by …”