Intelligent Biohybrid Materials for Therapeutic and Imaging Agent Delivery

Stayton, Patrick S.; Hoffman, Allan S.; El-Sayed, Mohamed; Kulkarni, Samarth; Shimoboji, Tsuyoshi; Murthy, Niren; Bulmuş, Volga; Lackey, Chantal A.

doi:10.1109/jproc.2005.844619

Cited by 29 publications

(10 citation statements)

References 32 publications

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“…Recently, stimuli-responsive, ''smart'' polymers have been investigated for drug and gene delivery because these polymers offer the opportunity to modulate their physicochemical properties within the tumor microenvironment (18)(19)(20)(21)(22)(23), and therefore, enhance the delivery of their therapeutic payload within a specific tumor compartment. We are interested in a class of thermally responsive macromolecules called elastin-like polypeptides (ELPs) as drug carriers because ELPs combine the passive targeting afforded by the enhanced permeability and retention effect with active thermal targeting using externally focused hyperthermia (19,24).…”

Section: Introductionmentioning

confidence: 99%

Thermal Cycling Enhances the Accumulation of a Temperature-Sensitive Biopolymer in Solid Tumors

et al. 2007

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The delivery of anticancer therapeutics to solid tumors remains a critical problem in the treatment of cancer. This study reports a new methodology to target a temperatureresponsive macromolecular drug carrier, an elastin-like polypeptide (ELP) to solid tumors. Using a dorsal skin fold window chamber model and intravital laser scanning confocal microscopy, we show that the ELP forms micron-sized aggregates that adhere to the tumor vasculature only when tumors are heated to 41.5°C. Upon return to normothermia, the vascular particles dissolve into the plasma, increasing the vascular concentration, which drives more ELPs across the tumor blood vessel and significantly increases its extravascular accumulation. These observations suggested that thermal cycling of tumors would increase the exposure of tumor cells to ELP drug carriers. We investigated this hypothesis in this study by thermally cycling an implanted tumor in nude mice from body temperature to 41.5°C thrice within 1.5 h, and showed the repeated formation of adherent microparticles of ELP in the heated tumor vasculature in each thermal cycle. These results suggest that thermal cycling of tumors can be repeated multiple times to further increase the accumulation of a thermally responsive polymeric drug carrier in solid tumors over a single heat-cool cycle. More broadly, this study shows a new approach-tumor thermal cycling-to exploit stimuli-responsive polymers in vivo to target the tumor vasculature or extravascular compartment with high specificity. [Cancer Res 2007;67(9):4418-24]

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Section: Introductionmentioning

confidence: 99%

Thermal Cycling Enhances the Accumulation of a Temperature-Sensitive Biopolymer in Solid Tumors

et al. 2007

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“…Control is achieved by tailoring the structure, size, and the specific polymeric matrix of the particles 1, 2. Additionally, polymeric particles with unique mechanical, magnetic, and optical properties can be used in the fields of physics, chemistry, and biology 3–5. Traditionally, polymeric particles have been produced by solvent extraction/evaporation, spray drying, and suspension/emulsion polymerization 6–8.…”

Section: Introductionmentioning

confidence: 99%

Polymeric particle formation through electrospraying at low atmospheric pressure

Kennedy

Clark

2008

J Biomed Mater Res

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Electrospraying is a simple and versatile technique capable of producing polymeric particles. However, most investigations carried out thus far have been performed at ambient atmospheric pressure without studying the influences of pressure on the formation of polymeric particles. Here, we report our investigation on the effects of varying the pressure and the solution concentration on the microstructures of electrosprayed polymeric particles. Pressures are varied from ambient atmospheric pressure to 380 mmHg below ambient pressure, and solution concentrations are varied over a range of 3-7 w/v %. By varying these parameters, we manipulated the rate of solvent evaporation and the solidification of the electrosprayed particles. The results show that changes to the pressure had significant effects on the microstructure and morphology of poly(epsilon-caprolactone) (PCL) particles. The average particle size became larger as the chamber pressure decreased. At a solution concentration of 5 w/v % and a pressure 150 mmHg below ambient pressure, uniform and spherical PCL particles were generated. Electrospun fibers were formed when a solution concentration of 7 w/v % was used. The developed technique can be applied to prepare polymeric drug delivery carriers though a low-pressure-assisted spray-drying method, and is particularly suitable for fabricating delivery microspheres encapsulated with temperature-sensitive drugs and biomolecules.

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“…Hoffman and Stayton pioneered the early development of responsive polymerprotein conjugates in the early 1980s 7,24 by developing covalent and non-covalent coupling methods, comparing random and site-specific attachment, and incorporating various stimuli-responsive polymers. A variety of applications were envisaged for polymer-protein conjugates, including recovery of enzymes from complex solutions, molecular sensing and controlled protein binding (vide infra) 6 .…”

Section: Synthetic Strategies For Bioconjugationmentioning

confidence: 99%

Smart hybrid materials by conjugation of responsive polymers to biomacromolecules

et al. 2014

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The chemical structure and function of biomacromolecules has evolved to fill many essential roles in biological systems. More specifically, proteins, peptides, nucleic acids and polysaccharides serve as vital structural components, and mediate chemical transformations and energy/information storage processes required to sustain life. In many cases, the properties and applications of biological macromolecules can be further expanded by attaching synthetic macromolecules. The modification of biomacromolecules by attaching a polymer that changes its properties in response to environmental variations, thus affecting the properties of the biomacromolecule, has led to the emergence of a new family of polymeric biomaterials. Here, we summarize techniques for conjugating responsive polymers to biomacromolecules and highlight applications of these bioconjugates reported so far. In doing so, we aim to show how advances in synthetic tools could lead to rapid expansion in the variety and uses of responsive bioconjugates.

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Intelligent Biohybrid Materials for Therapeutic and Imaging Agent Delivery

Cited by 29 publications

References 32 publications

Thermal Cycling Enhances the Accumulation of a Temperature-Sensitive Biopolymer in Solid Tumors

Thermal Cycling Enhances the Accumulation of a Temperature-Sensitive Biopolymer in Solid Tumors

Polymeric particle formation through electrospraying at low atmospheric pressure

Smart hybrid materials by conjugation of responsive polymers to biomacromolecules

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