Hydrogel-nanoparticle composites for optically modulated cancer therapeutic delivery

Abstract

A poly(N-isopropylacrylamide-co-acrylamide) (NIPAAm-co-AAm) hydrogel with near-infrared (NIR) absorbing silica-gold nanoshells was designed as a platform for pulsatile delivery of cancer therapeutics. This hydrogel was designed to have a lower critical solution temperature (LCST) above physiologic temperature, such that the material will transition from a hydrated state to a collapsed state above ~40 °C. Additionally, the silica-gold nanoshells used were designed to have a peak extinction coefficient in the NIR, where penetration of light through tissue is maximal. This heat-triggered material phase transition of the composite was found to follow exposure of NIR light, indicating the ability of the NIR absorption by the nanoshells to sufficiently drive this transition. The composite material was loaded with either doxorubicin or a DNA duplex (a model nucleic acid therapeutic), two cancer therapeutics with differing physical and chemical properties. Release of both therapeutics was dramatically enhanced by NIR light exposure, causing 2-5x increase in drug release. Drug delivery profiles were influenced by both the molecular size of the drug as well as its chemical properties. The DNA therapeutic showed slower rates of nonspecific delivery by passive diffusion due to its larger size. Additionally, only 70% of the more hydrophobic doxorubicin was released from the material, whereas the more hydrophillic DNA showed over 90% release. Further, hydrogel composites were used to deliver the doxorubicin to CT.26-WT colon carcinoma cells, eliciting a therapeutic response. This work validates the potential application for this material in site-specific cancer therapeutic delivery.

Carbohydrate polymer based pH-sensitive IPN microgels: Synthesis, characterization and drug release characteristics

“…Over the past decades, different polymeric therapeutics have begun to make a vital contribution for tumor targeting in cancer therapy. In cancer drug delivery, different polymer based hydrogels have been designed and demonstrated as drug carrier systems [4] [5] [6,7] [8]. Among the several polymeric systems developed, systems containing biodegradable polymers have been used for localized drug delivery to control therapeutic drug level over a period of months, since the degradation of polymer is slow [9].…”

Photo-triggerable hydrogel–nanoparticle hybrid scaffolds for remotely controlled drug delivery

“…Such depot formulations have recently gained attention for modulating drug release. 25, 26 However, compared to previous reports, we employed a robust synthetic strategy to stably link chemotherapeutic drugs to the nanoparticle surface, while simultaneously allowing for controlled drug release from the hydrogel upon photo-irradiation. The combination of these discrete components in a single hybrid system provided a number of advantages compared to conventional approaches, including chemical control over drug loading and release, negligible release in the absence of photo-irradiation, ease in adjusting drug release kinetics and high stability for long-term studies.…”

Novel Nanomaterials Enable Biomimetic Models of the Tumor Microenvironment

“…For example, one group synthesized a poly(N-isopropylacrylamide)-(pNIPAAm-) based hydrogel with lower critical solution temperature (LCST) above physiologic temperature, and thus, the gel swells when in the body. Gold nanoshells are incorporated within the hydrogel, along with doxorubicin (DOX), such that near-infrared (NIR) irradiation heats up the gel past the LCST, collapsing it and releasing the DOX [46]. is strategy has been used with other styles of gold nanoparticles to the same end [47].…”