Low-Fouling Gold Nanorod Theranostic Agents Enabled by a Sulfoxide Polymer Coating

Abstract

Gold nanorods (GNRs) are widely used in various biomedical applications such as disease imaging and therapy due to their unique plasmonic properties. To improve their bioavailability, GNRs often need to be coated with hydrophilic polymers so as to impart stealth properties. Poly(ethylene glycol) (PEG) has been long used as such a coating material for GNRs. However, there is increasing acknowledgement that the amphiphilic nature of PEG facilitates its interaction with protein molecules, leading to immune recognition and consequent side effects. This has motivated the search for new classes of low-fouling polymers with high hydrophilicity as alternative low-fouling surface coating materials for GNRs. Herein, we report the synthesis, characterization, and application of GNRs coated with highly hydrophilic sulfoxide-containing polymers. We investigated the effect of the sulfoxide polymer coating on the cellular uptake and in vivo circulation time of the GNRs and compared these properties with pegylated GNR counterparts. The photothermal effect and photoacoustic imaging of these polymer-coated GNRs were also explored, and the results show that these GNRs are promising as nanotheranostic particles for the treatment of cancer.

Stimuli-Responsive Sulfoxide Polymer–Protein Conjugates with Improved Pharmacokinetics and Tumor Delivery

“…Despite the Tf-PMSEA 4.8k conjugate being able to improve the in vivo pharmacokinetics of the protein, its performance fell slightly behind Tf-POEGA 16.2k with only a 1.4-fold increase in the t 1/2,β of the protein. This observation is consistent with the in vitro cellular results where Tf-POEGA 16.2k appeared to be more low-fouling compared to the Tf-PMSEA 4.8k conjugate having similar grafting density and chain length of conjugated polymers . Notably, the pharmacokinetic data obtained using the Cy5 signal arising from attached polymers revealed similar circulation trends to the results obtained utilizing Cy7.5 from the protein (Figure S28), suggesting that the conjugates were stable during circulation in the bloodstream.…”

“…This observation is consistent with the in vitro cellular results where Tf-POEGA 16.2k appeared to be more lowfouling compared to the Tf-PMSEA 4.8k conjugate having similar grafting density and chain length of conjugated polymers. 64 Notably, the pharmacokinetic data obtained using the Cy5 signal arising from attached polymers revealed similar circulation trends to the results obtained utilizing Cy7.5 from the protein (Figure S28), suggesting that the conjugates were stable during circulation in the bloodstream. The ex vivo biodistribution analysis performed 48 h post injection by measuring the fluorescence (Cy7.5 on Tf) of Tf and Tfpolymer conjugates in organs through IVIS optical imaging further confirmed the pharmacokinetic findings (Figure S29).…”

“…As is evident from Figure b, the uptake of the Tf-PMSEA 16.2k conjugate in both cell lines was significantly lower than that of Tf-POEGA 16.2k after a 6 h incubation time, confirming the superior low-fouling capability of PMSEA. The cellular uptake of the Tf-PMSEA 4.8k conjugate was slightly higher than that of Tf-POEGA 16.2k , likely due to the Tf-POEGA 16.2k conjugate having higher surface coverage of polymer due to the longer side chains of OEGA ( M n = 480 g/mol) compared to that of the MSEA monomer (162 g/mol), despite the chains having the same DP . On the contrary, despite the difference in the polymer chain length resulting from varying molecular weights of the monomeric units of OEGA and MSEA, both Tf-PMSEA 16.2k and Tf-POEGA 16.k exhibit comparable polymer molecular weights, ensuring sufficient surface coverage.…”

“…The cellular uptake of the Tf-PMSEA 4.8k conjugate was slightly higher than that of Tf-POEGA 16.2k , likely due to the Tf-POEGA 16.2k conjugate having higher surface coverage of polymer due to the longer side chains of OEGA (M n = 480 g/mol) compared to that of the MSEA monomer (162 g/mol), despite the chains having the same DP. 64 On the contrary, despite the difference in the polymer chain length resulting from varying molecular weights of the monomeric units of OEGA and MSEA, both Tf-PMSEA 16.2k and Tf-POEGA 16.k exhibit comparable polymer molecular weights, ensuring sufficient surface coverage. Therefore, the superior low-fouling nature of PMSEA can be predominantly attributed to its high hydrophilicity, resulting in reduced nonspecific protein adsorption compared to that of POEGA.…”

Recent Advances in Antifouling Surface Polymer Brushes

“…This highlighted the strong hydration behavior of PMSEA across a wide range of temperatures beneficial for biological applications. PMSEA has been used as a new class of hydrophilic coating material to nanoparticles and protein molecules to enable the development of advanced imaging agents and therapeutics with improved imaging capabilities, pharmacokinetics, and delivery efficiencies. − Xu et al investigated for the first time the potential of PMSEA as a new class of surface antifouling polymers. , They prepared PMSEA polymer brushes by conducting surface-initiated PET-RAFT polymerization of MSEA using glass slips as the planar substrate, and compared the hydrophilic and antifouling properties with the surfaces modified with poly­(oligo­(ethylene glycol) methyl ether acrylate) (POEGA) brushes (Figure ). Their results showed the PMSEA polymer brushes were more hydrophilic than POEGA brushes of the same chain lengths.…”