Biodegradable zwitterionic sulfobetaine polymer and its conjugate with paclitaxel for sustained drug delivery

Abstract

A fully biodegradable zwitterionic polymer and the corresponding conjugate with paclitaxel (PTX) were synthesized as promising biomaterials. Allyl-functionalized polylactide (PLA) was employed as the precursor of polymer backbones. UV-induced thiol-ene reaction was conducted to conjugate thiol-functionalized sulfobetaine (SB) with the PLA-based backbone. The resulting zwitterionic polymer did not exhibit considerable cytotoxicity. A polymer-drug conjugate was also obtained by thiol-ene reaction of both thiol-functionalized SB and PTX with allyl-functionalized PLA. The conjugate could readily form narrowly-dispersed nanoparticles in aqueous solutions with a volume-average hydrodynamic diameter (Dh,V) of 19.3 ± 0.2 nm. Such a polymer-drug conjugate-based drug delivery system showed full degradability, well-suppressed non-specific interaction with biomolecules, and sustained drug release. In vitro assessments also confirmed the significant anti-cancer efficacy of the conjugate. After 72 h incubation with PLA-SB/PTX containing 10 μg/mL of PTX, the cell viabilities of A549, MCF7, and PaCa-2 cells were as low as 20.0 ± 2.5 %, 1.7 ± 1.7 %, and 14.8 ± 0.9 %, respectively. Both flow cytometry and confocal microscopy suggested that the conjugates could be easily uptaken by A549 cells before the major release of PTX moieties. Overall, this work elucidates promising potentials of biodegradable zwitterionic polymer-based materials in biomedical applications.

Zwitterionic Polymer-Gated Au@TiO2 Core-Shell Nanoparticles for Imaging-Guided Combined Cancer Therapy

“…Herein, we loaded doxorubicin (DOX) into the Au@TiO 2 core-shell, then grafted the zwitterionic polymer onto the NP for combined cancer therapy. As the cancer cells' metabolism and the immune response contribute to an acidity tumor microenvironment 33, 34, the zwitterionic polymers convert to a cationic state when in proximity of the tumor tissues. The cationic nature of the polymer, not only enhances cellular uptake due to the strengthened NP-cellular membrane interactions, but also inhibits the cell growth.…”

Polyethyleneimine-Oleic Acid Micelles-Stabilized Palladium Nanoparticles as Highly Efficient Catalyst to Treat Pollutants with Enhanced Performance

“…These hydrodynamic diameters of the prepared PO-PdNPs were smaller than that of the PEI-oleic acid micelles, which should be attributed to PdNPs located in the PEI-oleic acid micelles’ shell. The measured hydrodynamic diameters of the prepared PO-PdNPs was larger than the TEM particle size measured in the dry state [ 23 , 24 ]. Figure 4 b showed that the zeta potential of PO-PdNPs n was 21.5, 25.55, and 31.1 mV at a molar ratio of [N]:[Pd] = 75, 100, and 150, respectively.…”

Galactosamine-Conjugating Zwitterionic Block Copolymer for Reduction-Responsive Release and Active Targeted Delivery of Doxorubicin to Hepatic Carcinoma Cells

“…Moreover, without detectable immune response and avoiding ABC phenomenon, zwitterionic polymers have been also identified as better biointerface material alternative PEG [11,12]. Recently, a variety of zwitterionic therapeutic nanoparticles, such as polymer-drug conjugates [13], nanogels [14], and polymeric micelles [15] have been developed. However, overcoming their less efficient tumor cell uptake is still a challenge [16].…”