The unexplored potential of gas‐responsive polymers in drug delivery: progress, challenges and outlook

Abstract

Targeted drug delivery based on polymeric nanoparticles has been a long‐standing interest in nanomedicine for its beneficial traits including controlled and localized drug release. Gas‐responsive polymers offer an advantageous platform and have been slowly gaining attention in spatially locating and displaying unique interactions of specific responsive chemical entities in polymeric chains with endogenous gaseous stimuli. In this review, we highlight recent developments in polymeric nanoformulations with stimulant chemical entities for gasotransmittors such as NO, CO, H2S, SO2, O2 and CO2 in enhancing efficacy in therapeutic interventions. We underline some challenges and limitations of exploring these systems for clinical applications, and how we can further tap into the potential of these emerging materials. © 2021 Society of Industrial Chemistry.

CO2-responsive gels

“…4 These materials find utility in a wide range of current and emerging applications [4][5][6] such as catalysis, 7 controlled drug delivery, [8][9][10] artificial muscles, 2,[11][12][13] and sensors. [14][15][16] Stimuli that have been explored include light, [17][18][19] pH, [20][21][22] redox, [23][24][25] temperature, [26][27][28] electric current, [29][30][31] magnetic field, 32 mechanical activation, [33][34][35] ultrasonication, [36][37][38] biological factors, [39][40][41] and various gases, 42,43 e.g., 1 O 2 , 44 O 2 , 45 O 2 /N 2 , 46,47 and O 2 /CO 2 . 48,49 This review focuses on...…”

Polymersomes: Soft Nanoparticles from Miktoarm Stars for Applications in Drug Delivery

“…A series of poly­(ethylene glycol)−polystyrene−poly­(2-( N , N -diethylamino)­ethyl methacrylate) (PEG−PS−PDEA) miktoarm star polymers (Figure ) with PDEA chains of varied molecular weight ( M n ) were synthesized, and their responsivity to CO 2 was examined . The gas responsivity (related to the presence of the PDEA arm) increased with an increase in M n of the PDEA arm. Interaction with dissolved CO 2 leads to protonation of PDEA, which makes it hydrophilic, and it can protrude to the surface to be in contact with the aqueous environment.…”

Single Functional Group Platform for Multistimuli Responsivities: Tertiary Amine for CO2/pH/ROS-Triggered Cargo Release in Nanocarriers

“…Polymeric nanoparticles (NPs) have advanced a viable approach in delivering poorly water-soluble drugs, reducing their undesired toxicity, and helping facilitate clinical translation. − To enhance the efficacy of drug delivery nanotechnologies, significant emphasis has been placed on exploiting pathological alterations at disease locations including low pH, elevated reactive oxygen species (ROS) concentrations, higher temperatures, and so forth by incorporating selective chemical entities into their macromolecular precursors to achieve targeted delivery. − Such nanocarriers typically respond well to specific endogenous cues to enhance drug release. , Due to insufficient biological understanding and complex double-edged behavior of biologically active gases, studies on gas-responsive polymers for drug delivery are progressing at a relatively slow pace. − As a regulator of blood pH, CO 2 exists mainly in three different forms in the body: in a hydrated state (HCO 3 – ), bound to hemoglobin (carbamate), and as dissolved CO 2 . At disease sites, especially tumor, the build-up of CO 2 (hypercapnia) tends to be associated with acidosis and hypoxia, which can confer chemoresistance in lung cancer cells, as well as aggravate pancreatic cancer. , On top of that, the overproduction of ROS, such as hydrogen peroxide (H 2 O 2 ), superoxide (O 2 – ), hydroxy radicals (•OH), and singlet oxygen ( 1 O 2 ) can cause dysfunctions that can be observed in pathologies such as cardiovascular and neurodegenerative diseases, diabetes, and aging. − As such, changes in CO 2 , pH, and ROS concentrations constitute important markers in the microenvironments at disease sites.…”