Marine and freshwater mussels secrete proteinaceous adhesive materials for adherence to the substrates upon which they reside. It is well known that 3,4-dihydroxyphenylalanine (DOPA) is the key to understanding these mussel adhesive proteins (MAPs). In order to gain a better understanding of their complex formation and quick recovery upon rupturing, novel water soluble copolymers of N-isopropylacrylamide and dopamine methacrylate were synthesized in such a way that they have 1, 2.5, and 5 mole percent dopamine monomer with respect to the NIPAM monomer on average. The statistical distribution of DOPA-functionalities along the chain makes the material a close synthetic equivalent of the byssal thread proteins of mytili. At acidic pH, the aqueous copolymer solution behaves like an unentangled copolymer solution, but at basic pH, these catechol functionalities form a dicomplex with H₃BO₃, thereby crosslinking two chains, proven by ¹¹B-NMR and gelation. The polymer solution is thermosensitive with a pH-dependent lower critical solution temperature (LCST) between 21 and 33 °C, depending on the DOPA-content. If 2 or more functionalities per chain are present, a gel is formed that is self-healing with very quick recovery from sustained damage. The moduli of the gels depend on the concentration of functionalities. Hence, triple stimuli responsive copolymers were obtained.

This study reports on an intelligent composite hydrogel with both pH-dependent drug release in a cancer environment and heat generation based on NIR laser exposure, for the combined application of photothermal therapy (PTT) and multidrug chemotherapy. For the first time in the literature, Dopamine nanoparticle (DP) was incorporated as a highly effective photothermal agent as well as anticancer drug, bortezomib (BTZ) carrier inside a stimuli responsive pNIPAAm-co-pAAm hydrogel. When light is applied to the composite hydrogel, DP nanoparticle absorbs the light, which is dissipated locally as heat to impact cancer cells via hyperthermia. On the other hand, facile release of the anticancer drug BTZ from the surface of DP encapsulated hydrogel could be achieved due to the dissociation between catechol groups of DP and the boronic acid functionality of BTZ in typical acidic cancer environment. In order to increase the synergistic effect by dual drug delivery, Doxorubicin (DOXO) were also loaded to pNIPAAm-co-pAAm/DP-BTZ hydrogel and the effect of monotherapy as well as combined therapy were detailed by a complete characterization. Our results suggest that these mussel inspired nanocomposite with excellent heating property and controllable multidrug release can be considered as a potential material for cancer therapy.

Continuous measurement of proteins in vivo is important for real-time disease management and prevention. Implantable sensors for monitoring small molecules such as glucose have been available for more than a decade. However, analysis of proteins remains an unmet need because the lower physiological levels require that sensors have high affinities, which are linked to long complexation half-lives ( t _1/2 ~20 hours) and slow equilibration when concentrations decrease. We report active-reset sensors by use of high-frequency oscillations to accelerate dissociation, which enables regeneration of the unbound form of the sensor within 1 minute. When implemented within implanted devices, these sensors allow for real-time, in vivo monitoring of proteins within interstitial fluid. Active-reset protein sensors track biomarker levels on a physiological timescale for inflammation monitoring in living animals.