Biocompatible PEG-Chitosan@Carbon Dots Hybrid Nanogels for Two-Photon Fluorescence Imaging, Near-Infrared Light/ pH Dual-Responsive Drug Carrier, and Synergistic Therapy

Stimuli-responsive nanogels have gained signifi cant progress because of their great potential for applications in intelligent drug delivery and other biomedical fi elds. [ 1–4 ] Recently, much attention has been focused on the integration of stimuli-responsive polymer nanogels with inorganic nanoparticles (NPs) to combine the biosensing or bioimaging ability with the controlled drug delivery function. [ 5–10 ] A key attribute of such responsive hybrid nanogels as drug delivery systems is their ability to regulate the drug release under specifi c environments or stimuli, which can signifi cantly improve the therapeutic effi cacy at pathological sites but reduce the systemic side effects. [ 11 ] Both endogenous and exogenous activations can be used to regulate the drug release from their carriers. [ 12–14 ] The endogenous activation can be realized by the variation of specifi c physiochemical characteristics of the pathological microenvironment. [ 15–17 ] For example, many pathological processes in tumor tissue and intracellular endosome/lysosome decrease the local pH by 1–2.5 pH units or increase the local temperature by 1–5 °C in comparison with that of blood and normal tissues. [ 18–20 ] On the other hand, the exogenous activation that can remotely control the drug release at a desired site and time is considered crucial to boost the drug effi cacy in cancer treatment while minimizing side effects. [ 21–26 ] Among all external stimuli including light and magnetic fi eld, near-infrared (NIR) light is the most favored for controlling the drug release due to its simple operation, low energy absorption, maximum penetration, and minimum side effects for human tissue and organs. [ 27,28 ] So far, nanostructured gold (Au) has been commonly integrated into the stimuli-responsive polymer nanogels to realize simultaneous NIR light-triggered drug release and cell imaging. [ 29–34 ] However, several disadvantages are associated with the noble metal NPs for their use in biomedical areas, including the Biocompatible PEG-Chitosan@Carbon Dots Hybrid Nanogels for Two-Photon Fluorescence Imaging, Near-Infrared Light/pH Dual-Responsive Drug Carrier, and Synergistic Therapy