Highly Efficient Intracellular Drug Delivery with a Negatively Charged Hyperbranched Polysulfonamine

Abstract

Efficient intracellular translocation is achieved using an easily prepared hyperbranched polysulfonamine that remains negatively charged at physiological pH. Investigations on the cellular uptake mechanism and the subcellular distribution of PSA are reported. The in vitro cytotoxicity of PSA is found to be low. Using doxorubicin as a model drug, a PSA/drug complex is prepared by electrostatic interaction with a high drug payload that exhibits a controlled release in response to pH. Efficient intracellular drug delivery, strong growth inhibition of tumor cells, and low cytotoxicity to normal cells are observed. The results suggest a possible way to utilize anionic polymers for intracellular delivery of therapeutic moieties or drugs. magnified image

Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval

“…Endosomes and the tumor microenvironment where the local pH is slightly acidic are the targeted spaces for such pHsensitive polymers. Several pH-sensitive polymers have been employed in polymeric micelle formulations including polycations such as poly(histidine) [131], poly(4-vinylpyridine) [132], poly(N,N-dimethylaminoethylmethacrylate) [133], poly(β-amino ester) (PBAE) [134], and polyanions, such as poly(acrylic acid) [135], poly(methacrylic acid) (PMAA) [136], and poly(sulfonamides) [137].…”

Hyperbranched Macromolecules: From Synthesis to Applications

“…In the bio-imaging field, HM-probe-conjugates with good water solubility and available functional groups are good solutions to problems associated with low quantum yield and poor specificity. Zhu and Yan grafted fluorescein isothiocyanate on peripheral hyperbranched polysulfonamine (HPSA) through the reaction of isothiocyanate and a primary amino group [ 128 , 129 ]. With low cytotoxicity and good serum compatibility, the HPSA-probe conjugate can be used for bio-imaging or for tracking cells [ 125 ].…”

Host–guest binding motifs based on hyperbranched polymers

“…Doxorubicin (DOX) is one of the most widely used guests among these hydrophobic drugs. Various HBPs including HPAMAM, 22 hyperbranched polyacetals (HBPAs), 21 hyperbranched polyester, 15,[18][19][20][111][112][113] selenium-containing hyperbranched polymers, 76,114 hyperbranched poly(amine-ester)s, 115 hyperbranched polyphosphates, [116][117][118] hyperbranched polysulfonamine, 119 backbone redox-responsive HBPs 120 have been used to construct diverse core-shell structures loaded with DOX. These DOX loaded core-shell structures can improve the solubility of DOX with a prolonged circulation time.…”