Nanohydrogels as A Prospective Member of The Nanomedicine Family

Abstract

modification (to escape from recognition by the reticuloendothelial system) and drug targeting by conjugation of ligand onto the surface of hydrogel nanoparticles to aim the corresponding biomarkers that are overexpressed in the cancer cell membrane. In the past decade, nanohydrogels have been under intensive investigation as a versatile tool for the delivery of advanced biological therapeutics such as proteins, peptides and carbohydrates. Even for oligonucleotides, a few attempts have been made for the delivery of siRNA [3–6]. Physical hydrogels and their biomedical applications have been intensively investigated in recent years. Fang et al. fabricated a honokiol (HK) nanoparticles loaded thermosensitive PEG-poly(e-caprolactone) (PCL)-PEG (PECE) hydrogel (HK-hydrogel), and demonstrated that such a hydrogel composite has outstanding therapeutic effects on malignant pleural effusion. Compared with the use of HK nanoparticles alone, blank hydrogel or normal saline, the HK-hydrogel system has distinct advantages in reducing the number of pleural tumor foci, prolonging survival time and inhibiting angiogenesis of pleural tumors [7]. Yang et al. also found that the thermosensitive PECE hydrogel has a notable efficacy in preventing post-surgical abdominal adhesions [8]. Additionally, Fu et al. tried to enlarge the application of PECE hydrogel in the bone tissue engineering field. Nanohydroxyapatite or acellular bone matrix were incorporated into a PECE hydrogel to form an injectable thermoresponse nano-hydroxyapatite or acellular bone matrix/PECE hydrogel composite [9]. Chemical hydrogels are commonly waterswollen networks of hydrophilic homopolymers or Molecular biomaterials, such as synthetic or natural biodegradable polymers, are the material basis of nanomedicine [1]. Among them, hydrophilic polymers, such as poly(ethylene glycol) (PEG), can be crosslinked to form a hydrogel, which is a 3D network that may absorb water in quantities from a few percent to thousands of times their dry weight. The amount of expansion is determined by the number of crosslinked molecules and the type of composite hydrophilic polymers or copolymers. Hydrogels can be either physical (reversible) gels, when the networks are held together by molecular entanglements and/or secondary forces including ionic or hydrophobic forces, or chemical (permanent) gels, when they are covalently crosslinked networks. Since the 1960s, hydrogels have had wide applications in biomedical engineering, especially in local drug delivery and tissue engineering for tissue repair and regeneration [2]. Recently, nanohydrogels, in other words hydrogel nanoparticles in the nanometer scale from tens to hundreds of nanometers, have become a member of great potential in the nanomedicine family. Among the various nanomedicine formulations, nanohydrogels have shown great advantages for delivery of hydrophilic small-molecule drugs and protein/peptide therapeutics due to their huge loading capacity of water-soluble compounds. Nanohydrogels combine the advantages of hydrogels and nanoparticles for drug formulation and delivery, which include controllable drug release, high stability in physiological media, distinct responsiveness to environmental factors such as pH and temperature, high cellular uptake due to the endocytosis mechanisms, long half-life in circulation by appropriate surface