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

Abstract

Diverse gases (NO, CO, H2S, H2, etc.) have been widely applied in the medical intervention of various diseases, including cancer, cardiovascular disease, ischemia‐reperfusion injury, bacterial infection, etc., attributing to their inherent biomedical activities. Although many gases have many biomedical activities, their clinical use is still limited due to the rapid and free diffusion behavior of these gases molecules, which may cause potential side effects and/or ineffective treatment. Gas‐generating nanoplatforms (GGNs) are effective strategies to address the aforementioned challenges of gas therapy by preventing gas production or release at nonspecific sites, enhancing GGNs accumulation at targeted sites, and controlling gas release in response to exogenous (UV, NIR, US, etc.) or endogenous (H2O2, GSH, pH, etc.) stimuli at the lesion site, further maintaining gas concentration within the effective range and achieving the purpose of disease treatment. This review comprehensively summarizes the advancements of “state‐of‐the‐art” GGNs in the recent three years, with emphasis on the composition, structure, preparation process, and gas release mechanism of the nanocarriers. Furthermore, the therapeutic effects and limitations of GGNs in preclinical studies using cell/animal models are discussed. Overall, this review enlightens the further development of this field and promotes the clinical transformation of gas therapy.

Ultrasound nanomedicine and materdicine

“…Gas molecules such as nitric oxide (NO), hydrogen (H 2 ), carbon monoxide (CO), oxygen, hydrogen sulfide (H 2 S) and sulfur dioxide (SO 2 ) are capable of regulating various physiological functions, including nervous system, cardiovascular system and immune system, which play an important role in the normal operation of human physiological processes and active regulation of pathological processes. 119,120 In addition, the adjustment of gas concentration in TME can affect the Wahlberg effect, thereby inhibiting the proliferation process and accelerating the cell apoptosis, while the activity and physiological function of normal cells are not affected. 121 Therefore, gas therapy has been developed as a safe and effective ''green'' cancer treatment.…”

Rapidly Blocking the Calcium Overload/ROS Production Feedback Loop to Alleviate Acute Kidney Injury via Microenvironment‐Responsive BAPTA‐AM/BAC Co‐Delivery Nanosystem

“…[13] However, due to the fact the solubility of H 2 in the biological environment is typically low (≈0.8 mm, RT), the amount of H 2 absorbed by the body via inhalation routes is insufficient to eliminate the excess ROS produced under pathological conditions. [11,14] More targeted nanocarriers have been designed and applied in recent years to deliver H 2 or H 2 -producing prodrugs to injured cells, rapidly releasing high concentrations of H 2 that diffuse throughout multiple organelle regions of the cell, assuring efficient scavenging of excess ROS. [15] Despite the fact that ROS scavenging can successfully prevent oxidative stress injury, intracellular Ca 2+ overload will continue to stimulate mitochondrial ROS production and exacerbate Ca 2+ inward flow.…”

“…As a ROS depleting agent, hydrogen (H 2 ) has many unique advantages, including: (1) easily penetrating biological membranes and rapidly diffusing into the cytoplasm, mitochondria, and nucleus; [ 11 ] (2) selective reduction of hydroxyl radicals (·OH), which effectively protects cells without interfering with metabolic redox reactions or disrupting other ROS involved in cell signaling; [ 12 ] and (3) H 2 is a safe gas with no significant adverse effects on humans. [ 13 ] However, due to the fact the solubility of H 2 in the biological environment is typically low (≈0.8 m m , RT), the amount of H 2 absorbed by the body via inhalation routes is insufficient to eliminate the excess ROS produced under pathological conditions.…”

Tumor-penetrating nanoplatform with ultrasound “unlocking” for cascade synergistic therapy and visual feedback under hypoxia

“…In brief, the design of an optimized nanoplatform to achieve the full delivery of O 2 and enhanced relevant therapeutic effects should include (i) nanoplatforms for excellent tumor penetration depth and endocytosis, (ii) a controlled O 2 -supplying nanoplatform-vehicle and visually monitored system, and (iii) a nanoplatform-based cascade therapeutic strategy, providing a significant therapeutic effect on hypoxic tumors. Nanoultrasonic biomedicines, including low-diffusion liquid perfluorocarbon (PFC)-based nanodroplets, have been designed for US-activated specific drug release, molecular imaging, SDT, etc [18][19][20][21][22]. Moreover, after US activation, the nanodroplets reach a certain threshold; thus, a large amount of liquid PFC is converted into a gaseous state, and a final rupture occurs due to vibration and expansion, resulting in an ultrasonic cavitation effect, which is also known as acoustic droplet vaporization (ADV), to achieve highly selective drug release and responsive imaging in a pathological tissue [23,24].…”