Triggering Mechanisms of Thermosensitive Nanoparticles Under Hyperthermia Condition

doi:10.1002/jps.24536

Journal of Pharmaceutical Sciences

Volume 104, Issue 8, August 2015, Pages 2414-2428

https://doi.org/10.1002/jps.24536 Get rights and content

Abstract

Nanoparticle-based hyperthermia is an effective therapeutic approach that allows time- and site-specific treatment with minimized off-site effects. The recent advances in materials science have led to design a diversity of thermosensitive nanostructures that exhibit different mechanisms of thermal response to the external stimuli. This article aims to provide an extensive review of the various triggering mechanisms in the nanostructures used as adjuvants to hyperthermia modalities. Understanding the differences between various mechanisms of thermal response in these nanostructures could help researchers in the selection of appropriate materials for each experimental and clinical condition as well as to address the current shortcomings of these mechanisms with improved material design.

Section snippets

INTRODUCTION

Nanoparticle-based drug delivery is an innovative method that has been employed to achieve reduced systemic toxicity, improved drug retention in circulation, and increased intratumoral drug accumulation via the enhanced permeability and retention effect.¹ However, the structure heterogeneity of tumor vasculature inflicts an irregular drug extravasation within the infected region.2., 3. Moreover, because of the complexity of interstitial tumor matrix as well as the limited interstitial fluid

COIL–GLOBULE PHASE TRANSITION

Coil–globule phase transition of the thermosensitive polymers has recently found increasing interest for effective release of therapeutics under hyperthermia condition. The unique characteristic of thermosensitive polymers is their discontinuous water-solubility change at a specific temperature referred to as the critical solution temperature (CST). In the concentration–temperature phase diagrams, CST is a temperature where both coil-shaped soluble polymer chains and insoluble polymer globules

MEMBRANE DISRUPTION

Drug release by dissociation of the nanocarriers at hyperthermia temperature range is a triggering mechanism that is mostly observed in thermosensitive liposomes (TSLs). Liposomes are spherical vesicles consisted of aqueous interior cores surrounded by lipid bilayer shells (Fig. 3a) that form by self-assembly of amphiphilic lipids in aqueous solutions.⁵⁷

The enhanced delivery of anticancer drugs into tumor tissue using TSLs and hyperthermia was firstly reported in 1978.⁵⁸ Afterwards, various

MICELLIZATION

Aqueous solutions of some amphiphilic polymers exhibit thermal-triggered micellization by hydrophobic effect at temperatures and concentrations higher than their critical micellar temperature (CMT) and critical micellar concentration (CMC), respectively. In general, the hydrogels composed of polymer chains without covalent cross-links may exhibit micellization behavior rather than coil–globule transition. Moreover, the content of hydrophilic moieties may favor the micellization behavior. For

SUPERPARAMAGNETIC BEHAVIOR

Magnetic hyperthermia is a treatment modality that employs external AMF with appropriate frequency and strength to heat a magnetic nanofluid dispersed within the target tissue. The produced thermal energy is further transferred to the surrounding region, whereby maintaining the temperature within the therapeutic threshold (40°C–42°C) for above 30 min could induce apoptosis and effectively killing of the tumor.138., 139. This technique shows the potential to overcome the limitations of other

PHOTO ABSORBANCE

Photothermal cancer therapy is an innovative modality in which the incident light beam is absorbed by chromophoric molecules within the tumor and converted to thermal energy.151., 152. This technique often employs the light beams with wavelengths in the near-infrared (NIR) window (650–900 nm) where the maximum tissue penetration is gained because of a moderate tissue transparency at this wavelength range.¹⁵³ Scattering is the dominant light–tissue interaction in the NIR window that result in a

DISCUSSION AND CONCLUSION

The present work aimed to review the triggering mechanisms of thermosensitive nanoparticles that have been specifically used as adjuvants in hyperthermia and thermal therapy treatments. In addition to general properties such as biocompatibility, biodegradability, facile production, reproducibility, and mechanical stability in physiological environment, the substantial influential features in clinical success of these actuation mechanisms are zero-order function in physiological temperature, as

AKNOWLEDGMENTS

This research was supported by the High Impact Research, Ministry of Higher Education (MOHE) Malaysia (grant no. UM.C/HIR/MOHE/DENT/14).

The authors do not report any conflict of interests.

REFERENCES (192)

L. Li et al.
Improved intratumoral nanoparticle extravasation and penetration by mild hyperthermia
J Control Release
(2013)
R.D. Issels
Hyperthermia adds to chemotherapy
Eur J Cancer
(2008)
J. Li et al.
Possibility of active targeting to tumor by local hyperthermia with temperature-sensitive nanoparticles
Med Hypotheses
(2008)
Y. Qiu et al.
Environment-sensitive hydrogels for drug delivery
Adv Drug Deliv Rev
(2001)
T. Ta et al.
Thermosensitive liposomes for localized delivery and triggered release of chemotherapy
J Control Release
(2013)
U. Kedar et al.
Advances in polymeric micelles for drug delivery and tumor targeting
Nanomed Nanotechnol Biol Med
(2010)
P. Cherukuri et al.
Targeted hyperthermia using metal nanoparticles
Adv Drug Deliv Rev
(2010)
C.S.S.R. Kumar et al.
Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery
Adv Drug Deliv Rev
(2011)
I. Sharifi et al.
Ferrite-based magnetic nanofluids used in hyperthermia applications
J Magn Magn Mater
(2012)
R. Singh et al.
Carbon nanotubes in hyperthermia therapy
Adv Drug Deliv Rev
(2013)

D. Schmaljohann

Thermo-and pH-responsive polymers in drug delivery

Adv Drug Deliv Rev

(2006)

C. Scherzinger et al.

Cononsolvency of poly- N-isopropyl acryl amide (PNIPAM): Microgels versus linear chains and macrogels

Curr Opin Colloid Interface Sci

(2014)

P. Li et al.

Thermosensitive poly (N-isopropylacrylamide-co-glycidyl methacrylate) microgels for controlled drug release

Colloids Surf B Biointerfaces

(2013)

H. Katono et al.

Thermo-responsive swelling and drug release switching of interpenetrating polymer networks composed of poly (acrylamide-co-butyl methacrylate) and poly (acrylic acid)

J Control Release

(1991)

R. Xie et al.

Preparation of thermo-responsive gating membranes with controllable response temperature

J Membr Sci

(2007)

J. Zhang et al.

Dual thermo-and pH-sensitive poly (N- isopropylacrylamide-co-acrylic acid) hydrogels with rapid response behaviors

Polymer

(2007)

D. Needham et al.

The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors

Adv Drug Deliv Rev

(2001)

L.M. Hays et al.

Factors affecting leakage of trapped solutes from phospholipid vesicles during thermotropic phase transitions

Cryobiology

(2001)

Y. Nibu et al.

Effect of headgroup type on the miscibility of homologous phospholipids with different acyl chain lengths in hydrated bilayer

Biophys Chem

(1995)

L. Li et al.

Triggered content release from optimized stealth thermosensitive liposomes using mild hyperthermia

J Control Release

(2010)

L. Li et al.

Mild hyperthermia triggered doxorubicin release from optimized stealth thermosensitive liposomes improves intratumoral drug delivery and efficacy

J Control Release

(2013)

H. Wang et al.

Folate-PEG coated cationic modified chitosan–cholesterol liposomes for tumor-targeted drug delivery

Biomaterials

(2010)

S. Zalipsky et al.

Evaluation of blood clearance rates and biodistribution of poly(2-oxazoline)-grafted liposomes

J Pharm Sci

(1996)

A. Yamazaki et al.

Modification of liposomes with N-substituted polyacrylamides: Identification of proteins adsorbed from plasma

Biochim Biophys Acta Biomembr

(1999)

B. Romberg et al.

Pharmacokinetics of poly (hydroxyethyl-l-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration

Biochim Biophys Acta Biomembr

(2007)

B. Romberg et al.

Enzyme-induced shedding of a poly (amino acid)-coating triggers contents release from dioleoyl phosphatidylethanolamine liposomes

Int J Pharm

(2008)

M. de Smet et al.

Magnetic resonance imaging of high intensity focused ultrasound mediated drug delivery from temperature-sensitive liposomes: An in vivo proof-of-concept study

J Control Release

(2011)

J.K. Mills et al.

Lysolipid incorporation in dipalmitoylphosphatidylcholine bilayer membranes enhances the ion permeability and drug release rates at the membrane phase transition

Biochim Biophys Acta Biomembr

(2005)

K. Kono

Thermosensitive polymer-modified liposomes

Adv Drug Deliv Rev

(2001)

W. Zhou et al.

Characteristics, phase behavior and control release for copolymer–liposome with both pH and temperature sensitivities

Colloids Surf Physicochem Eng Aspects

(2012)

K. Kono et al.

Effect of poly (ethylene glycol) grafts on temperature- sensitivity of thermosensitive polymer-modified liposomes

J Control Release

(2002)

H.D. Han et al.

Hyperthermia-induced antitumor activity of thermosensitive polymer modified temperature-sensitive liposomes

J Pharm Sci

(2006)

K. Kono et al.

Temperature-sensitive liposomes: Liposomes bearing poly (N-isopropylacrylamide)

J Control Release

(1994)

L. Pradhan et al.

pH- and thermosensitive thin lipid layer coated mesoporous magnetic nanoassemblies as a dual drug delivery system towards thermochemotherapy of cancer

Acta Biomater

(2014)

M.R. Faria et al.

Synthesis and characterization of magnetoliposomes for MRI contrast enhancement

Int J Pharm

(2013)

R.K. Jain et al.

Delivering nanomedicine to solid tumors

Nat Rev Clinl Oncol

(2010)

P.W. Vaupel et al.

Pathophysiological and vascular characteristics of tumours and their importance for hyperthermia: Heterogeneity is the key issue

Int J Hyperthermia

(2010)

A. Chrastina et al.

Overcoming in vivo barriers to targeted nanodelivery

Wiley Interdiscip Rev Nanomed Nanobiotechnol

(2011)

A. Hervault et al.

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer

Nanoscale

(2014)

J.P. May et al.

Hyperthermia-induced drug targeting

Expert Opin Drug Deliv

(2013)

S. Mura et al.

Stimuli-responsive nanocarriers for drug delivery

Nat Mater

(2013)

M.A. Ward et al.

Thermoresponsive polymers for biomedical applications

Polymers

(2011)

C. Gong et al.

Thermosensitive polymeric hydrogels as drug delivery systems

Curr Med Chem

(2013)

B. Kneidl et al.

Thermosensitive liposomal drug delivery systems: State of the art review

Int J Nanomedicine

(2014)

B.M. Dicheva et al.

Targeted thermosensitive liposomes: An attractive novel approach for increased drug delivery to solid tumors

Expert Opin Drug Deliv

(2014)

S. Croy et al.

Polymeric micelles for drug delivery

Curr Pharm Des

(2006)

M. Talelli et al.

Thermosensitive polymeric micelles for targeted drug delivery

Nanomedicine

(2011)

T.B. Huff et al.

Hyperthermic effects of gold nanorods on tumor cells

Nanomedicine

(2007)

J.-H. Lee et al.

Exchange-coupled magnetic nanoparticles for efficient heat induction

Nat Nanotechnol

(2011)

R. Klingeler et al.

Carbon nanotube based biomedical agents for heating, temperature sensoring and drug delivery

Int J Hyperthermia

(2008)

Cited by (18)

Thermosensitive poly(N-isopropylacrylamide) hydrogel/highly internal phase emulsion porous polymer tube tip solid-phase extraction for the determination of methylimidazoles in beverage
2023, Journal of Chromatography A
Poly(N-isopropylacrylamide) thermosensitive hydrogel tube tip solid-phase extraction/ultra-high liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for analysis of methylimidazoles in beverages. Thermosensitive poly(N-isopropylacrylamide) (PNIPA) hydrogel solid-phase extraction (SPE) medium was prepared on the surface of highly internal phase emulsion (HIPE) porous polymer by thermally initiated polymerization in a tube tip. The temperature sensitive SPE medium has the characteristics of high porosity and high specific surface area. When the temperature is higher than 30.0℃, it can well adsorb polar molecular, and could quickly desorb polar molecular when the temperature was less than 20.0℃. The tube tip SPE coupled with UPLC-MS/MS method was established for the determination of three polar molecules including 1-methylimidazole, 4-methylimidazole and 2-methylimidazole, with linear ranges of 2.50 – 240 μg/L, and detection limits of 1.20, 1.20 and 0.65 μg/L, respectively. The method was applied to the determination of three methylimidazoles in beverages with the spiked recoveries of 81.5%-115.5% and the RSD of 0.6%-5.0%, and the relative errors of the results with the national standard UPLC-MS/MS method were in the range of -8.5%-8.9%.
Advances in anti-breast cancer drugs and the application of nano-drug delivery systems in breast cancer therapy
2020, Journal of Drug Delivery Science and Technology
Citation Excerpt :
In 1978, Yatvin and coworkers [90] proposed a thermosensitive liposomal formulation of dipalmitoyl phosphatidylcholine (DPPC) and distearoyl phosphatidylcholine (DSPC) at a molar ratio of 3:1, and this was the first thermosensitive liposomal preparation. The heat source that triggers the rupture of the thermosensitive liposomes is usually generated by superparamagnetic materials or substances that can absorb light [91]. It has been found that thermosensitive liposomes allow image-guided drug delivery, in which the drugs delivered to the target tissue can be identified by medical imaging.
Breast cancer is one of the most common malignant tumors among women. Although the traditional breast cancer therapies are effective, there have numerous shortcomings, including low bioavailability and significant side effects. Nano-drug delivery systems have numerous advantages, including proper tumor targeting, high bioavailability, reduced side effects, controlled drug release, and increased drug solubility. The delivery of anti-breast cancer drugs via nano-drug delivery systems has become a research hotspot in the recent years. By performing a literature survey and summarizing the relevant studies by authors within and outside China, this article reviews the progress of current research on anti-breast cancer drugs and the application of nano-drug delivery systems in breast cancer therapy. The review aims to provide novel concepts for the design of nanocarriers for the delivery of anti-breast cancer drugs.
Investigation of nanoscale zerovalent iron-based magnetic and thermal dual-responsive composite materials for the removal and detection of phenols
2018, Chemosphere
Citation Excerpt :
During the swell-shrink process, the controlled release of some target substances could be conducted (Li and Guan, 2011). Therefore, PNIPAM and similar copolymers have gained popularity from researchers for application in targeted drug delivery, detection of proteins, and so on in the biomedical field (Dabbagh et al., 2015; Razmjou et al., 2013). Yin et al. researched the application of PNIPAM in indium tin oxide film for the release of incorporated hemoglobin (Yin et al., 2014b).
In this study, well-defined magnetic and thermal dual-responsive nanomaterials were synthesized, which contained ultrafine core-shell Fe@SiO₂ nanoparticles as magnetic core and poly(N-isopropylacrylamide) (PNIPAM) as thermosensitive outer shell. The fabricated nanoparticles were characterized and investigated for the adsorption of four phenolic compounds, including bisphenol A (BPA), tetrabromobisphenol A (TBBPA), 4-tert-octylphenol (4-OP) and 4-n-nonylphenol (4-NP). The experimental results demonstrated that the excellent adsorption rates were attributed to hydrophobic effect, hydrogen-bonding interaction, and electrostatic attraction. The adsorption process followed pseudo-second-order kinetics model and nonlinear isotherms, indicating heterogeneous adsorption process. The adsorption efficiency of 4-NP using Fe@SiO₂@PNIPAM was more than 90% under optimized condition within 2 h. The determined maximum adsorption amounts of BPA, TBBPA, 4-OP and 4-NP were 2.43, 6.83, 24.75, and 49.34 mg g⁻¹, respectively. Meanwhile, a magnetic solid phase extraction (MSPE) method with Fe@SiO₂@PNIPAM was established to determine these four compounds simultaneously. Under the optimal conditions, the linearity ranges were in the range of 2–200, 2–300, 2–100 and 2–100 μg L⁻¹ for BPA, 4-OP, TBBPA, and 4-NP, respectively, and the detection limits were in the range of 0.58–0.76 μg L⁻¹, respectively. The applicability of the proposed method was evaluated by analyzing three fresh water samples, and satisfactory spiked recoveries in the range 70.9–119.9% were achieved. It was proved that these adsorbents could be easily collected and recycled owing to the appropriate magnetism. The results also demonstrated that the as-prepared adsorbents had promising potential in the enrichment and analysis of detrimental organic pollutants from water.
Vesicle-based drug carriers
2018, Design and Development of New Nanocarriers
Phospholipids, block copolymers and surfactants are surface-active molecules that assemble into bilayer structures in aqueous solutions, forming nanoscale vesicles: phospholipid-based liposomes, polymer-based polymersomes, or surfactant-based niosomes. These vesicles are highly versatile and can be used for the delivery of pharmaceutical agents—enabling targeted and controlled release while shielding the encapsulated drugs from environmental degradation agents and the immune system. The performance of vesicle-based drug carriers has been shown to depend on both their constituent chemistry (e.g., surface moieties) and their physical properties (size, shape). This review examines the characteristics of vesicle-based formulations and their application to biomedical applications ranging from cancer therapies to delivery across the blood–brain barrier (BBB).
Smart chemistry-based nanosized drug delivery systems for systemic applications: A comprehensive review
2017, Journal of Controlled Release
Citation Excerpt :
The ability of PNIPAM to precipitate at body temperature, which is above its lower critical solution temperature (LCST), makes it suitable for systemic applications. However, one of the main drawbacks of PNIPAM is its limited biodegradability under in vivo conditions [285]. There are numerous other polymers that exhibit similar gelling behavior, such as pluronic (PEG-PPG-PEG), hyper-branched polyether, hyper-branched poly(amine ester), and elastin-like polypeptides (ELPs) [286–288].
This review focuses on the smart chemistry that has been utilized in developing polymer-based drug delivery systems over the past 10 years. We provide a comprehensive overview of the different functional moieties and reducible linkages exploited in these systems, and outline their design, synthesis, and application from a therapeutic efficacy viewpoint. Furthermore, we highlight the next generation nanomedicine strategies based on this novel chemistry.
Drug releasing nanoplatforms activated by alternating magnetic fields
2017, Biochimica et Biophysica Acta - General Subjects
The use of an alternating magnetic field (AMF) to generate non-invasively and spatially a localized heating from a magnetic nano-mediator has become very popular these last years to develop magnetic hyperthermia (MH) as a promising therapeutic modality already used in the clinics. AMF has become highly attractive this last decade over others radiations, as AMF allows a deeper penetration in the body and a less harmful ionizing effect. In addition to pure MH which induces tumor cell death through local T elevation, this AMF-generated magneto-thermal effect can also be exploited as a relevant external stimulus to trigger a drug release from drug-loaded magnetic nanocarriers, temporally and spatially. This review article is focused especially on this concept of AMF induced drug release, possibly combined with MH. The design of such magnetically responsive drug delivery nanoplatforms requires two key and complementary components: a magnetic mediator which collects and turns the magnetic energy into local heat, and a thermoresponsive carrier ensuring thermo-induced drug release, as a consequence of magnetic stimulus. A wide panel of magnetic nanomaterials/chemistries and processes are currently developed to achieve such nanoplatforms. This review article presents a broad overview about the fundamental concepts of drug releasing nanoplatforms activated by AMF, their formulations, and their efficiency in vitro and in vivo. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editors: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

View all citing articles on Scopus

View full text

ReviewTriggering Mechanisms of Thermosensitive Nanoparticles Under Hyperthermia Condition

Abstract

Section snippets

INTRODUCTION

COIL–GLOBULE PHASE TRANSITION

MEMBRANE DISRUPTION

MICELLIZATION

SUPERPARAMAGNETIC BEHAVIOR

PHOTO ABSORBANCE

DISCUSSION AND CONCLUSION

AKNOWLEDGMENTS

J Control Release

Eur J Cancer

Med Hypotheses

Adv Drug Deliv Rev

J Control Release

Nanomed Nanotechnol Biol Med

Adv Drug Deliv Rev

Adv Drug Deliv Rev

J Magn Magn Mater

Adv Drug Deliv Rev

Adv Drug Deliv Rev

Curr Opin Colloid Interface Sci

Colloids Surf B Biointerfaces

J Control Release

J Membr Sci

Polymer

Adv Drug Deliv Rev

Cryobiology

Biophys Chem

J Control Release

J Control Release

Biomaterials

J Pharm Sci

Biochim Biophys Acta Biomembr

Biochim Biophys Acta Biomembr

Int J Pharm

J Control Release

Biochim Biophys Acta Biomembr

Adv Drug Deliv Rev

Colloids Surf Physicochem Eng Aspects

J Control Release

J Pharm Sci

J Control Release

Acta Biomater

Int J Pharm

Delivering nanomedicine to solid tumors

Nat Rev Clinl Oncol

Pathophysiological and vascular characteristics of tumours and their importance for hyperthermia: Heterogeneity is the key issue

Int J Hyperthermia

Overcoming in vivo barriers to targeted nanodelivery

Wiley Interdiscip Rev Nanomed Nanobiotechnol

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer

Nanoscale

Hyperthermia-induced drug targeting

Expert Opin Drug Deliv

Stimuli-responsive nanocarriers for drug delivery

Nat Mater

Thermoresponsive polymers for biomedical applications

Polymers

Thermosensitive polymeric hydrogels as drug delivery systems

Curr Med Chem

Thermosensitive liposomal drug delivery systems: State of the art review

Int J Nanomedicine

Targeted thermosensitive liposomes: An attractive novel approach for increased drug delivery to solid tumors

Expert Opin Drug Deliv

Polymeric micelles for drug delivery

Curr Pharm Des

Thermosensitive polymeric micelles for targeted drug delivery

Nanomedicine

Hyperthermic effects of gold nanorods on tumor cells

Nanomedicine

Exchange-coupled magnetic nanoparticles for efficient heat induction

Nat Nanotechnol

Carbon nanotube based biomedical agents for heating, temperature sensoring and drug delivery

Int J Hyperthermia

Review
Triggering Mechanisms of Thermosensitive Nanoparticles Under Hyperthermia Condition