Hyperthermia and Temperature-Sensitive Nanomaterials for Spatiotemporal Drug Delivery to Solid Tumors

Abstract

Nanotechnology has great capability in formulation, reduction of side effects, and enhancing pharmacokinetics of chemotherapeutics by designing stable or long circulating nano-carriers. However, effective drug delivery at the cellular level by means of such carriers is still unsatisfactory. One promising approach is using spatiotemporal drug release by means of nanoparticles with the capacity for content release triggered by internal or external stimuli. Among different stimuli, interests for application of external heat, hyperthermia, is growing. Advanced technology, ease of application and most importantly high level of control over applied heat, and as a result triggered release, and the adjuvant effect of hyperthermia in enhancing therapeutic response of chemotherapeutics, i.e., thermochemotherapy, make hyperthermia a great stimulus for triggered drug release. Therefore, a variety of temperature sensitive nano-carriers, lipid or/and polymeric based, have been fabricated and studied. Importantly, in order to achieve an efficient therapeutic outcome, and taking the advantages of thermochemotherapy into consideration, release characteristics from nano-carriers should fit with applicable clinical thermal setting. Here we introduce and discuss the application of the three most studied temperature sensitive nanoparticles with emphasis on release behavior and its importance regarding applicability and therapeutic potentials.

Externally triggered smart drug delivery system encapsulating idarubicin shows superior kinetics and enhances tumoral drug uptake and response

“…Smart drug delivery systems (SDDS), therefore, have been developed where content release can be activated by an external trigger, enabling delivery of free drug at a high concentration to a relatively small tissue volume and in short time-frame 18 , 19 . Because of the versatile nature of lipid-based SDDS, clinical applicability, and high compatibility, thermosensitive liposomes are the most advanced 20 - 23 .…”

Caffeic Acid Phenethyl Ester-Incorporated Radio-Sensitive Nanoparticles of Phenylboronic Acid Pinacol Ester-Conjugated Hyaluronic Acid for Application in Radioprotection

“…Since CAPE itself is a lipophilic agent and is hardly dissolved in an aqueous solution, nanoparticles can solve these problems, i.e., nanoparticles enable us to dissolve CAPE in an aqueous solution [28]. Furthermore, nanoparticles can be modified to be sensitive to physicochemical stimulus such as radiation, pH, ROS, magnetic field, and light [32][33][34][35][36][37]. HAsPBPE nanoparticles can respond to ROS since the PBPE moiety and thiol group in TbEA in the polymer backbone are known to have ROS-sensitivity and these moieties are able to be decomposed in the oxidative stress [45].…”

“…Nano-dimensional vehicles such as nanoparticles, polymeric micelles, liposomes or colloidal carriers have been extensively investigated in the diverse field of biomedical science [28][29][30][31][32]. Especially, nanoparticles have been frequently considered for stimulisensitive drug delivery of bioactive agents, i.e., they can be modified to respond against the stimulus in the biological system such as acidic pH, temperature, magnetic field, oxidative stress, light, and irradiation [32][33][34][35][36][37]. For example, Choi et al reported that iron oxide-incorporated lipocomplexes respond to the magnetic field, concentrate around the tumor mass, and then specifically target cancer [32].…”

A Tri-Stimuli Responsive (Maghemite/PLGA)/Chitosan Nanostructure with Promising Applications in Lung Cancer

“…The release media were either C 6 H 8 O 7 -Na 2 HPO 4 or C 6 H 8 O 7 -NaOH buffers reproducing the pH of bloodstream (7.4 ± 0.1) or the acidic microenvironment in tumours (pH 5.0 ± 0.1) [ 80 ], respectively. These in-vitro drug release media were kept either at the normal human body-temperature (normothermia or euthermia, 37.0 ± 0.5 °C), or at the representative temperature of magnetic hyperthermia-triggered drug release experiments (45.0 ± 0.5 °C) [ 81 , 82 , 83 ]. The latter temperature is also the characteristic maximum hyperthermia temperature of magnetic colloids commonly used as magnetic hyperthermia agents for cancer treatment [ 83 , 84 ].…”