Dual pH- and Glutathione-Responsive CO₂-Generating Nanodrug Delivery System for Contrast-Enhanced Ultrasonography and Therapy of Prostate Cancer

Abstract

Ultrasonography (US) contrast imaging using US contrast agents has been widely applied for the diagnosis and differential diagnosis of tumors. Commercial US contrast agents have limited applications because of their large size and shorter imaging time. At the same time, the desired therapeutic purpose cannot be achieved by applying only conventional US contrast agents. The development of nanoscale US agents with US imaging and therapeutic functions has attracted increasing attention. In this study, we successfully developed DOX-loaded poly-1,6-hexanedithiolsodium bicarbonate nanoparticles

The Advancement of Gas‐Generating Nanoplatforms in Biomedical Fields: Current Frontiers and Future Perspectives

“…Based on the slightly acidic microenvironment of the tumor, Li et al synthesized dual pH-and GSH-responsive DOX@HADT-SS-NaHCO 3 NPs through water/oil/water double emulsification which comprises the disulfide-containing polymer, sodium bicarbonate (NaHCO 3 ) aqueous solution, and Chemo drug DOX (Figure 8B-i). [164] Notably, NaHCO 3 can produce CO 2 under acidic conditions and provide an echo signal. The dual pH/GSH responsive drug release enabled precise gas delivery in the tumor site with longer and stronger effects, ultimately leading to the enhanced US imaging signal and prostate cancer therapy (Figure 8B-ii).…”

“…[74][75][76]86,[97][98][99]102,104,106,111,137,145,159] N 2 and CO 2 , as inert gases, are detected through US imaging and indirectly measured by the gray value of the imaging data. [161,163,164] All the above-mentioned gas detection methods can measure the amount of gas production from nanoparticles in vitro, which provide certain guidelines for the in vivo application of GGNs. In vivo monitoring of gases mainly adopts US imaging, and US signal intensity can also provide semi-quantitative value, providing a rough guide for estimating the dosage of GGNs required for disease treatment.…”

“…These nanoplatforms could precisely deliver therapeutic gases to the lesions and release gases in response to either external (light, US, magnetic, etc.) or internal stimulation (pH, GSH, Small Methods 2022, 6, 2200139 CO 2 Ultrasonic imaging Gray value semiquantitative calculation [163,164] In vivo real-time monitoring O 2 Ultrasonic imaging Gray value semi-quantitative calculation [28,33,38,42,50] H 2 Ultrasonic imaging Gray value semiquantitative calculation [128] Needle-type H 2 sensor Direct display of gas content [128,133] SO 2 Ultrasonic imaging Gray value semiquantitative calculation [158] N 2 Ultrasonic imaging Gray value semiquantitative calculation [161] CO 2 Ultrasonic imaging Gray value semiquantitative calculation [163] H 2 O 2 , etc.) without causing obvious toxicity to normal tissues.…”

“…Silymarin-loaded KMD / / 5 mg kg −1 of KMD Acute liver failure therapy [163] DOX@HADT-SS-NaHCO 3 / 5000 ppm (25 mg mL −1 of DOX@HADT-SS-NaHCO 3 ) 10 mg kg −1 of DOX Cancer therapy [164] DOX-DiR@cerasome / / 5 mg kg −1 of DOX Cancer therapy [165] Table 1. Continued.…”

Construction of Folate-Conjugated and pH-Responsive Cell Membrane Mimetic Mixed Micelles for Desirable DOX Release and Enhanced Tumor-Cellular Target

“…Moreover, to accelerate the intracellular release of the drug from the nanocarriers, and thus improve the therapeutic efficacy and reduce unwanted side effects, numerous stimuli-responsive (pH, redox, temperature, or a combination of them) carriers have been designed and researched systematically due to the different microenvironment of tumor tissues and normal tissues. − In particular, over the past decades, pH-responsive micelles based on polymers either with acid-labile bonds (ester, hydrazone, and acetal) or with ionizable groups (amines, carboxylic acid, or sulfonate acid) have been reported. 2-(Dimethylamino)­ethyl methacrylate (DMAEMA) is a polymeric monomer with a tertiary amine group, which can be protonated in an acidic medium.…”