The exogenous-triggered smart materials make it possible to prepare the DDS with real-time modulation of drug levels and can be complementary with the endogenous-triggered smart materials. Therefore, it is difficult for endogenous-triggered smart materials to develop drug delivery system (DDS) with predictable release kinetics and artificially controlled release after administration. And features of patients might vary from each other. 14 The pathophysiological features can be highly heterogeneous. And the main drug release mechanism of the formed bioresponsive nanocarriers or prodrugs can be summarized as endogenous-triggered carrier solubility change, endogenous-triggered carrier cleavage, or endogenous-triggered prodrug linker cleavage.Ĭomparing with endogenous-triggered smart materials, exogenous-triggered smart materials have their advantages of being stimulated at a desired time, location, and/or dose. These smart polymers can be further conducted into nanocarriers or prodrugs via appropriate fabrication methodologies. Generally, endogenous-triggered smart materials for drug delivery are always synthetic bioresponsive polymers that can be deconstructed into functional motifs with biological sensitivities and assistant structures such as polyethylene glycol (PEG) shell, targeting moieties and hydrophobic units. 11, 12 These smart materials with biocompatibility and degradability would show dramatic conformational changes when they response to mild physical/chemical. Typical stimulators applied to smart materials for cancer drug delivery include endogenous stimulators such as pH, reactive oxygen species (ROS), glutathione (GSH), hypoxia and enzyme, or exogenous stimulators such as temperature ( T), light, ultrasound (US), radiation, and magnetic field. 6, 7 Thus, the stimuli-sensitive nanocarriers possess desired and controlled cargo delivery, release, and activation in specific regions, facilitating powerful antitumor activities without harmful side effects on normal sites. Because the endogenous/exogenous responsive smart materials-based nanocarriers under rational design and implementation with tumor-specific drug delivery ability can surmount their barriers during circulation or in tumors, avoiding protein corona, enzymatic degradation, cargos leakage or burst release in undesired healthy tissues, prolonging blood circulation, as well as increasing tumor accumulation, etc. These smart materials are inspired to meet the demands of the booming nanocarriers that act as promising drug delivery vehicles to tumors. 2- 5 A major research focus is smart materials for cancer drug delivery. 1 More recently, the smart materials for stimuli-responsive applications of drug delivery, diagnostics, theranostics, tumor imaging, and biomedical devices have obtained growing development. The engineered materials used for spatially and/or temporally controlled drug release were first carried out in the 1970s.
It is hope that this timely and overall review would provide some helpful information for researchers in this field. The current situation and remaining challenges of stimuli-sensitive materials-based nanocarriers for clinical translation are discussed rationally at the end. We primarily focus on the studies in the past few years (2017-2020). In this review, significant research achievements of smart materials responsive to different triggers including their synthesis and formulation mechanism, responsive mechanism, applications, multiple functions are summarized and discussed separately.
Smart materials have attracted considerable attention because they provide likelihood strategy for individualized and comprehensive therapy. As footstone of stimuli-responsive nanocarriers, endogenous/exogenous responsive smart materials possess many properties, such as responding ability to specific triggers, controlled drug release, long blood circulation, increased tumor accumulation, “ON-OFF” switch activities, enhanced diagnostic accuracy, and therapeutic efficacy. Until now, enormous smart materials have been engineered with endogenous stimulators such as pH, reactive oxygen species, glutathione, hypoxia and enzyme, or exogenous stimulators such as temperature, light, ultrasound, radiation, and magnetic field in drug delivery.
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