Acylsulfonamide‐Functionalized Zwitterionic Gold Nanoparticles for Enhanced Cellular Uptake at Tumor pH

Abstract

We report here a nanoparticle design featuring pH-responsive alkoxyphenyl acylsulfonamide ligands. Due to ligand structure, this nanoparticle is neutral at pH 7.4, becoming positively charged at tumor pH (< 6.5). The particle uptake and cytotoxicity increases over this pH range. This pH-controlled uptake and toxicity makes this particle a promising tool for cancer therapeutics.Keywords pH responsive; zwitterionic; gold nanoparticles; acylsulfonamide; cellular uptakeThe pH difference between normal tissue (pH 7.2-7.4) and tumor tissue (pH 6.0-6.8) 1 provides an attractive strategy for selective accumulation of nanoparticles (NPs) into tumor tissues for cancer treatment and/or imaging. To supply high tumor selectivity, a pHresponsive bio-interactive surface must be generated with appropriate responses at normal and tumor pH. 2 The most common strategy is the use of a non-interactive functional group bearing an acid-cleavable unit; however, difficulty in controlling the acid sensitivity can result in the cleavage reaction taking place even at neutral pH, 3 or requiring quite low pH (≈ 5.0) for activation. 4 The use of reversible protonation/deprotonation systems provides an alternate strategy that features high tunablity. 5 Recent reports employing polymers such as poly-histidine and polyamines as a pH-responsive moieties provided high tumor pH sensitivity. 6 Solubility can be a challenge, however, with these neutral-to-cationic systems, requiring the use of additional functional group such as poly(ethylene)glycol chains at neutral pH.Zwitterionic surfaces have recently received considerable attention as non-interacting chemical surfaces. 7 NPs with zwitterionic surfaces exhibit a long circulatory half-life, 8 low

Size‐Dependent Cellular Uptake of DNA Functionalized Gold Nanoparticles

“…The extent and efficiency of cellular uptake is dependent in part on the physicochemical characteristics of the nanoparticle system, including particle size, shape,[4a,5] surface charge, and surface chemistry . Significant interplay between these factors is frequently observed, making identification of the effect of individual components complex.…”

How Does the Study MD of pH-Dependent Exposure of Nanoparticles Affect Cellular Uptake of Anticancer Drugs?

“…Our density curve shows that the parameters of our MD force field fit our problem well. However, in the case of the stomach, the pH model is destabilized during MD simulations because it is a highly acidic medium, as observed in this study [ 32 ]. The selection of the POPC membrane model is based on previous studies [ 35 ] on the role of anticancer drugs in the presence of cholesterol within the POPC membrane.…”

“…In our case, we observed the APL for two models of MTX-SS-PGA with pH values of 7.0 and 6.4 to be 63.94 Å 2 and 63.89 Å 2 at 313.15 K, respectively, as shown in Table 2 and Figure S1 (Supplementary Information) . The third model, with a pH of 2.0, destabilizes [ 32 ] the system due to the high acidic pH of the medium during the MD production run, indicating that the drug delivery process has started; we could not determine the area per lipid for this model. In addition, the electron density for each lipid layer (POPC) refers to the electron-rich phosphorus group in the head group region present at the maxima of the peaks on both sides of the membrane, defined by the D HH as the distance between the head-to-head maxima of the peaks.…”

Targeted dose enhancement in radiotherapy for breast cancer using gold nanoparticles, part 2: A treatment planning study

“…Tumor control probability and normal tissue complication probability have been evaluated as a function of GNP uptake selectivity in a breast cancer treatment planning investigation. Because of the increasing efforts to conjugate GNPs to targeting agents, [34][35][36][37] the model can provide a predictive framework for labeled GNP radiosensitization.…”