Temperature difference of the environment may have an effect on the CMC. The most common polymer is poly(N-isopropylacrylamide), which transforms to a hydrophobic insoluble polymer from hydrophilic polymer around 32°C. Soga et al. have developed another thermosensitive polymeric micelles [74—77].
A few studies indicate that hydrophobicity and hydrophilicity of nanomicelles can be shifted under light exposure. Briefly, nanomicelles can be disrupted or reversed by light. This property can be utilized to trigger drug release and delivery [78,79]. Andrew et al. have reported that the micellar system is very sensitive to infrared light causing release of fluorescence probe such as Nile red .
Ultrasound can generate a frequency around 20 kHz or more, which can be utilized to enhance tumor drug uptake. Ultrasound has enhanced drug delivery by inducing (1) deeper tissue penetration, (2) perturbation of normal and tumor cell membrane, and
(3) drug release from nanomicelle [81—85]. Marin et al. have studied the release and intracellular uptake of doxorubicin (Dox) from pluronic micelles, the most common ultrasound-sensitive nanomicelles. Higher Dox release from pluronic micelles was observed under high-frequency ultrasound .
Other stimuli-responsive nanomicelle systems have been studied including enzyme- and redox-responsive systems. Enzymes are known to overexpresses in tumor cells. The oxidative and reductive enzyme expressions vary between intracellular and extracellular environments. Those differences are utilized in developing nanomicelle carrier to deliver drugs to the target.
Multifunctional Nanomicelle Carrier
Multifunctional nanomicelle comprises at least two ligands. Multifunctional micelles could enhance the hydrophobic drug delivery to specific target. Moreover, it can carry imaging agents that enable nanomicelle tracking released by pH-sensitive polymer or ultrasound exposure. Li et al. have developed acid-sensitive nanomicelle for both targeted drug delivery and MRI in liver cancer cells . Doxorubicin and superparamagnetic iron oxide nanoparticles (imaging agents) were encapsulated inside poly(ethylene glycol)-b-poly(N-(N0,N0-diisopropylaminoethyl) glutamine) (PEG-P(GA-DIP)) and surface modified with folate acid for targeting. This multifunctional nanomicelle facilitated specific tumor targeting and enhanced therapeutic effect as well as MRI diagnosis.