| There are diverse clinical indications such as cancers,central nervous diseases,diabetes,and skeletal diseases that require a long-term performance of therapeutics.An ideal drug treatment to manage these diseases is to maintain the drugs locally for a long period and to control the drug release in an on-demand fashion.Hydrogels,mostly composed of hydrophilic polymers to form a three-dimensional network,have been well used as a matrix scaffold for local drug delivery.Stimuli-responsive hydrogels not only provide a spatial control of the release of therapeutics but also offer a temporal management of the release of drugs in response to different stimuli.Recent development of stimuli-responsive nanoscale systems,which are able to control the drug release in response to either exogenous stimuli such as light,magnetic field,and ultrasound or endogenous ones including pH,enzymes,and redox potential,provides materials and principles for the fabrication of stimuli-responsive hydtogels for drug delivery.Poly(ethylene glycol)(PEG)has been widely used as a polymer basis to fabricate hydrogels due to its unique properties including great biocompatibility,no adhesiveness to proteins and cells,and excellent hydrophilic nature.PEG based hydrogels have been used to deliver diverse therapeutic agents such as chemical drugs,proteins,oligonucleotides,and polysaccharides.Although PEG hydrogels arepromising for clinical applications,they still have some problems that need to be addressed.The first problem involves hydrogel fabrication.Cross-linking agents used to cross-link the PEG chains and the related chemical reactions might cause unexpected toxicity,resulting in reduced safety of the PEG hydrogels.The second issue is related to the control of drug release.Therapeutic agents are commonly physically entrapped in the network of PEG hydrogels,which complicates regulation of drug release with highly temporal resolution and is characterized by burst release at the beginning and slow leakage during the long time of implantation in the body.A third problem is that many PEG hydrogels are generally nondegradable.Although PEG is highly biocompatible,a permanent retention of PEG hydrogels in the body even after the complete release of drugs or the cure of diseases increases the risk of foreign-body reactions and other unexpected adverse effects.Therefore,additional research efforts are in demand to address these problems for the clinical translation of PEG hydrogels.Nanocomposite hydrogels that incorporate nanoparticles in their network via chemical or physical interactions might provide a new opportunity for the performance improvement of PEG hydrogels.Polydopamine(PDA),a major component of melanin,possesses excellent biocompatibility and is biodegradable in the body.Polydopamine nanoparticles(PDANPs)were reported to have high drug loading capability and photothermal effect.Additionally,chemicals with thiol or amine groups can be feasibly conjugated on the surface of PDANPs.In this study,we used PDANPs as a cross-linking agent to cross-link a thiol-terminated four-arm PEG(4-arm PEG-SH)to form a PDA/PEG hydrogel.The hydrogel was injectable and could be fabricated into different shapes.It also exhibited excellent biocompatibility and did not induce any foreign-body reaction over a 4-month implantation.Owing to the existence of PDANPs,the hydrogel could load anticancer drugs such as 7-ethyl-10-hydroxycamptothecin(SN38)and maintain the drug in the gel network for a long period,and further controlled the drug release in an on-demand manner upon near-infrared(NIK)irradiation.PDANPs also endowed the hydrogel excellent photothermal effect.A combined chemo-photothermal therapy mediated by the prepared hydrogel was conducted to ablate solid tumors. |
PDF Full Text Request