Nanomaterials: Versatile Drug Carriers for Nanomedicine
279
20 Temperature-Sensitive Systems
Temperature-sensitive method relays on the intrinsic properties or the microenvironment found in diseased tissue. It was perceived that in some malignant cancers (such
as prostate, bladder, etc.) and also some other ailment conditions appear to show some
local temperature difference than that of the normal tissues [122]. This difference in
temperature at the pathological sites helped to synthesize temperature-sensitive drug
delivery systems. The two fundamental types of thermo-sensitive materials based on
its potentiality to swell and de-swell to depend on the temperature, are—
1. Positive temperature-sensitive hydrogels—They are swollen as well as hydrated
at higher temperatures, and when cooled at upper critical solution temperature
(UCST), they contract.
2. Negative temperature-sensitive hydrogels—They swell at lower temperatures,
and as they are heated above the lower critical solution temperature (LCST),
they contract.
The nano-carriers made up of UCST/LCST polymers can respond to the changes
in temperature present in their microenvironment where the nano-systems alter
their characteristics such as solubility, conformation, and hydrophobic/hydrophilic
balance to deliver the therapeutic agents at the targeted sites [123]. Thermosensitive
liposomes are made up of DPPC/DSPC, the most common lipids. A temperaturedependent fusion of liposomes can be accomplished with the right composition of
lipids at a mild hyperthermia region (39–42 °C), which helps to enhance levels of
drug release at the infectious site [124]. In early in vivo work done in various tumor
models, including sarcomas, carcinomas, and lymph nodes metastasis, with a range
of drugs such as methotrexate, bleomycin, cisplatin, and adriamycin exhibited positive results of temperature-sensitive liposomes with mild hyperthermia [125, 126].
With an extensive study done, this gives a wide variety so as choose the design of
nano-carriers of desired architecture.
21 Targeting Hypoxia
Hypoxia is a condition when the concentration of oxygen is low. This plays a crucial
role in numerous tumors, which contributes to radio-resistance, chemoresistance,
vasculogenesis, angiogenesis, reluctant to cell death, invasiveness, genomic instability, and altered metabolism. In solid tumors, hypoxia lies in surrounding areas of
necrosis. A transcriptional factor, hypoxia-inducible factor (HIF), acts as a hypoxia
sensor in a cell. Overexpression of the regulatory subunit, HIF-α is a measure of escalated severity of tumor grade, vascular density, collapsing of conventional treatment,
and prognosis. Therefore, the use of HIF as a direct or indirect therapeutic agent has
become attractive over the years [127]. Thambi et al. reported hypoxia-responsive
self-assembled nanoparticles, which under hypoxia conditions release hydrophobic
279
20 Temperature-Sensitive Systems
Temperature-sensitive method relays on the intrinsic properties or the microenvironment found in diseased tissue. It was perceived that in some malignant cancers (such
as prostate, bladder, etc.) and also some other ailment conditions appear to show some
local temperature difference than that of the normal tissues [122]. This difference in
temperature at the pathological sites helped to synthesize temperature-sensitive drug
delivery systems. The two fundamental types of thermo-sensitive materials based on
its potentiality to swell and de-swell to depend on the temperature, are—
1. Positive temperature-sensitive hydrogels—They are swollen as well as hydrated
at higher temperatures, and when cooled at upper critical solution temperature
(UCST), they contract.
2. Negative temperature-sensitive hydrogels—They swell at lower temperatures,
and as they are heated above the lower critical solution temperature (LCST),
they contract.
The nano-carriers made up of UCST/LCST polymers can respond to the changes
in temperature present in their microenvironment where the nano-systems alter
their characteristics such as solubility, conformation, and hydrophobic/hydrophilic
balance to deliver the therapeutic agents at the targeted sites [123]. Thermosensitive
liposomes are made up of DPPC/DSPC, the most common lipids. A temperaturedependent fusion of liposomes can be accomplished with the right composition of
lipids at a mild hyperthermia region (39–42 °C), which helps to enhance levels of
drug release at the infectious site [124]. In early in vivo work done in various tumor
models, including sarcomas, carcinomas, and lymph nodes metastasis, with a range
of drugs such as methotrexate, bleomycin, cisplatin, and adriamycin exhibited positive results of temperature-sensitive liposomes with mild hyperthermia [125, 126].
With an extensive study done, this gives a wide variety so as choose the design of
nano-carriers of desired architecture.
21 Targeting Hypoxia
Hypoxia is a condition when the concentration of oxygen is low. This plays a crucial
role in numerous tumors, which contributes to radio-resistance, chemoresistance,
vasculogenesis, angiogenesis, reluctant to cell death, invasiveness, genomic instability, and altered metabolism. In solid tumors, hypoxia lies in surrounding areas of
necrosis. A transcriptional factor, hypoxia-inducible factor (HIF), acts as a hypoxia
sensor in a cell. Overexpression of the regulatory subunit, HIF-α is a measure of escalated severity of tumor grade, vascular density, collapsing of conventional treatment,
and prognosis. Therefore, the use of HIF as a direct or indirect therapeutic agent has
become attractive over the years [127]. Thambi et al. reported hypoxia-responsive
self-assembled nanoparticles, which under hypoxia conditions release hydrophobic