Stimuli-Responsive Small-on-Large Nanoradiosensitizer for Enhanced Tumor Penetration and Radiotherapy Sensitization

A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.

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Hierarchically stimuli-responsive nanovectors for improved tumor penetration and programed tumor therapy

Nanoscale ◽

10.1039/c8nr02971g ◽

2018 ◽

Vol 10 (28) ◽

pp. 13737-13750 ◽

Cited By ~ 14

Author(s):

Junjie Liu ◽

Xingming Guo ◽

Zhong Luo ◽

Jixi Zhang ◽

Menghuan Li ◽

...

Keyword(s):

Drug Delivery ◽

Solid Tumors ◽

Tumor Therapy ◽

Stimuli Responsive ◽

Antitumor Therapy ◽

Tumor Penetration

Poor drug delivery to solid tumors remains a great challenge for effective antitumor therapy.

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Stimuli-Sheddable Nanomedicine Overcoming Pathophysiological Barriers for Potentiating Immunotherapy of Cancer

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3134 ◽

2021 ◽

Vol 17 (8) ◽

pp. 1486-1509

Author(s):

Jiaxin Wang ◽

Mengxue Zhou ◽

Fangmin Chen ◽

Xiao Liu ◽

Jin Gao ◽

...

Keyword(s):

Immune Checkpoints ◽

Stimuli Responsive ◽

Tumor Penetration ◽

Cancer Management ◽

Formidable Challenge ◽

Critical Issues ◽

Immunotherapy Of Cancer ◽

Kynurenine Metabolism ◽

Endogenous Activity ◽

External Stimuli

Immunotherapy displays potent potential for clinical cancer management by activating the protective immune response; however, the microenvironment of the immunosuppressive tumor restricts the efficiency of immunotherapies. Along with the complex pathophysiological barrier of the solid tumors, successful immunotherapeutic delivery remains a formidable challenge for conventional nanomedicine. Stimuli-sheddable nano vectors may facilitate the delivery of cargoes to tumors with minimal premature cargo leakage in blood circulation while enhancing the tumor penetration of nanomedicines by deshielding the polyethylene glycol (PEG) corona upon endogenous activity such as acidity, enzymes and glutathione, or external stimuli, such as laser irradiation. Throughout this study, researchers overviewed the recent advances of nanomedicine-based cancer immunotherapy using the stimuli-responsive deshielding nano vectors, which allowed researchers to integrate multiple therapeutic regimens for inducing immunogenic cell death. This aided in blocking the immune checkpoints, repolarizing the macrophages, and regulating the kynurenine metabolism. Furthermore, researchers discussed the critical issues in the development of stimuli-sheddable nanoimmunodulators, primarily aimed at speeding up their clinical translation. Finally, researchers provided novel perspectives for improving cancer management with the stimuli-sheddable nanomedicine.

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Bio-stimuli-responsive multi-scale hyaluronic acid nanoparticles for deepened tumor penetration and enhanced therapy

Carbohydrate Polymers ◽

10.1016/j.carbpol.2017.05.017 ◽

2017 ◽

Vol 171 ◽

pp. 173-182 ◽

Cited By ~ 21

Author(s):

Mengmeng Huo ◽

Wenyan Li ◽

Arka Sen Chaudhuri ◽

Yuchao Fan ◽

Xiu Han ◽

...

Keyword(s):

Hyaluronic Acid ◽

Stimuli Responsive ◽

Tumor Penetration ◽

Multi Scale

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Amino-functional polyethers: versatile, stimuli-responsive polymers

Polymer Chemistry ◽

10.1039/d0py00466a ◽

2020 ◽

Vol 11 (24) ◽

pp. 3940-3950 ◽

Cited By ~ 2

Author(s):

Patrick Verkoyen ◽

Holger Frey

Keyword(s):

Ring Opening ◽

Review Article ◽

Stimuli Responsive ◽

New Class ◽

Stimuli Responsive Polymers ◽

Responsive Polymers

Amino-functional polyethers have emerged as a new class of “smart”, i.e. pH- and thermoresponsive materials. This review article summarizes the synthesis and applications of these materials, obtained from ring-opening of suitable epoxide monomers.

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4D printing technology, modern era: A short review

International Journal of Energy Technology ◽

10.32438//ijet.203015 ◽

2020 ◽

pp. 92-111

Author(s):

Khodadad Mostakim ◽

Nahid Imtiaz Masuk ◽

Md. Rakib Hasan ◽

Md. Shafikul Islam

Keyword(s):

Smart Materials ◽

Computer Aided Design ◽

Short Review ◽

Stimuli Responsive ◽

4D Printing ◽

Space Applications ◽

Printing Technology ◽

Practical Applications ◽

Biomedical Technologies ◽

Novel Material

The advancement in 3D printing has led to the rapid growth of 4D printing technology. Adding time, as the fourth dimension, this technology ushered the potential of a massive evolution in fields of biomedical technologies, space applications, deployable structures, manufacturing industries, and so forth. This technology performs ingenious design, using smart materials to create advanced forms of the 3-D printed specimen. Improvements in Computer-aided design, additive manufacturing process, and material science engineering have ultimately favored the growth of 4-D printing innovation and revealed an effective method to gather complex 3-D structures. Contrast to all these developments, novel material is still a challenging sector. However, this short review illustrates the basic of 4D printing, summarizes the stimuli responsive materials properties, which have prominent role in the field of 4D technology. In addition, the practical applications are depicted and the potential prospect of this technology is put forward.

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Synthesis of Smart Mesoporous Materials

MRS Proceedings ◽

10.1557/proc-775-p7.8 ◽

2003 ◽

Vol 775 ◽

Author(s):

G.V.Rama Rao ◽

Qiang Fu ◽

Linnea K. Ista ◽

Huifang Xu ◽

S. Balamurugan ◽

...

Keyword(s):

Mesoporous Silica ◽

Mesoporous Materials ◽

Fluorescent Dyes ◽

Thermo Gravimetric Analysis ◽

Molecular Transport ◽

Solute Diffusion ◽

Gravimetric Analysis ◽

Stimuli Responsive ◽

Porous Network ◽

Hybrid Mesoporous Materials

AbstractThis study details development of hybrid mesoporous materials in which molecular transport through mesopores can be precisely controlled and reversibly modulated. Mesoporous silica materials formed by surfactant templating were modified by surface initiated atom transfer radical polymerization of poly(N-isopropyl acrylamide) (PNIPAAm) a stimuli responsive polymer (SRP) within the porous network. Thermo gravimetric analysis and FTIR spectroscopy were used to confirm the presence of PNIPAAm on the silica surface. Nitrogen porosimetry, transmission electron microscopy and X-ray diffraction analyses confirmed that polymerization occurred uniformly within the porous network. Uptake and release of fluorescent dyes from the particles was monitored by spectrofluorimetry and scanning laser confocal microscopy. Results suggest that the presence of PNIPAAm, a SRP, in the porous network can be used to modulate the transport of aqueous solutes. At low temperature, (e.g., room temperature) the PNIPAAm is hydrated and extended and inhibits transport of analytes; at higher temperatures (e.g., 50°C) it is hydrophobic and is collapsed within the pore network, thus allowing solute diffusion into or out of the mesoporous silica. The transition form hydrophilic to hydrophobic state on polymer grafted mesoporous membranes was determined by contact angle measurements. This work has implications for the development of materials for the selective control of transport of molecular solutes in a variety of applications.

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Smart Polymers and their Applications: A Review

International Journal of Current Pharmaceutical Review and Research ◽

10.25258/ijcprr.v8i03.9220 ◽

2017 ◽

Vol 8 (03) ◽

Author(s):

Gore S. A. ◽

Gholve S. B. ◽

Savalsure S. M. ◽

Ghodake K. B. ◽

Bhusnure O. G. ◽

...

Keyword(s):

Oil Recovery ◽

Water Soluble ◽

Solution Temperature ◽

Smart Polymers ◽

Stimuli Responsive ◽

Responsive Materials ◽

Water Soluble Polymers ◽

Commercial Applications ◽

Stimuli Sensitive ◽

External Stimuli

Smart polymers are materials that respond to small external stimuli. These are also referred as stimuli responsive materials or intelligent materials. Smart polymers that can exhibit stimuli-sensitive properties are becoming important in many commercial applications. These polymers can change shape, strength and pore size based on external factors such as temperature, pH and stress. The stimuli include salt, UV irradiation, temperature, pH, magnetic or electric field, ionic factors etc. Smart polymers are very promising applicants in drug delivery, tissue engineering, cell culture, gene carriers, textile engineering, oil recovery, radioactive wastage and protein purification. The study is focused on the entire features of smart polymers and their most recent and relevant applications. Water soluble polymers with tunable lower critical solution temperature (LCST) are of increasing interest for biological applications such as cell patterning, smart drug release, DNA sequencing etc.

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Revisiting the High-Pressure Properties of the Metal-Organic Frameworks ZIF-8 and ZIF-67

10.26434/chemrxiv.13146278.v1 ◽

2020 ◽

Author(s):

Pia Vervoorts ◽

Stefan Burger ◽

Karina Hemmer ◽

Gregor Kieslich

Keyword(s):

High Pressure ◽

State Of The Art ◽

Energy Landscape ◽

Structural Flexibility ◽

Zeolitic Imidazolate Frameworks ◽

Stimuli Responsive ◽

X Ray Diffraction ◽

X Ray ◽

Open Questions ◽

Metal Organic

The zeolitic imidazolate frameworks ZIF-8 and ZIF-67 harbour a series of fascinating stimuli responsive properties. Looking at their responsitivity to hydrostatic pressure as stimulus, open questions exist regarding the isotropic compression with non-penetrating pressure transmitting media. By applying a state-of-the-art high-pressure powder X-ray diffraction setup, we revisit the high-pressure behaviour of ZIF-8 and ZIF-67 up to p = 0.4 GPa in small pressure increments. We observe a drastic, reversible change of high-pressure powder X-ray diffraction data at p = 0.3 GPa, discovering large volume structural flexibility in ZIF-8 and ZIF-67. Our results imply a shallow underlying energy landscape in ZIF-8 and ZIF-67, an observation that might point at rich polymorphism of ZIF-8 and ZIF-67, similar to ZIF-4(Zn).

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