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Biomimetic Engineering of a Scavenger‐Free Nitric Oxide‐Generating/Delivering System to Enhance Radiation Therapy
Author(s) -
Lin YuJung,
Chen ChunChieh,
Nguyen Dang,
Su HueiRou,
Lin KunJu,
Chen HsinLung,
Hu YuJung,
Lai PoLiang,
Sung HsingWen
Publication year - 2020
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202000655
Subject(s) - nitric oxide , plga , chemistry , in vivo , biophysics , aqueous solution , scavenger , pulmonary surfactant , molecule , radiosensitizer , nanotechnology , materials science , in vitro , radiation therapy , biochemistry , organic chemistry , radical , medicine , microbiology and biotechnology , biology
Nitric oxide (NO) is a potent tumor‐cell radiosensitizer but it can be readily scavenged by hemoglobin (Hb) in vivo. A biomimetic incubator that can generate and deliver NO in a scavenger (Hb)‐free environment to enhance its radiosensitizing effect to maximize its efficacy in radiotherapy is proposed. This NO incubator comprises a poly(lactic‐co‐glycolic acid) (PLGA) hollow microsphere (HM) that contains an NO donor (NONOate) and a surfactant molecule (sodium caprate, SC) in its aqueous core. In acidic tumorous environments, the PLGA shell of the HM allows the penetration of protons from the outside, activating the hydrolytic cleavage of NONOate, spontaneously generating NO bubbles, which are immediately trapped/stabilized by SC. The SC‐stabilized NO bubbles in the HM are then squeezed through the spaces of its PLGA matrices by the elevated internal pressure. Upon leaving the HM, the entrapped NO molecules may passively diffuse through their SC‐stabilized/protected layer gradually to the tumor site, having a long‐lasting radiosensitizing effect and inhibiting tumor growth. The entire process of NO generation and delivery is conducted in a scavenger (Hb)‐free environment, mimicking the development of young ovoviviparous fish inside their mothers' bodies in the absence of predators before birth.