Light‐based technique, including optical imaging and photoregulation, has become one of the most important tools for both fundamental research and clinical practice, such as cell signal sensing, cancer diagnosis, tissue engineering, drug delivery, visual regulation, neuromodulation, and disease treatment. In particular, low energy near‐infrared (NIR, 700–1700 nm) light possesses lower phototoxicity and higher tissue penetration depth in living systems as compared with ultraviolet/visible light, making it a promising tool for in vivo applications. Currently, the NIR light‐based imaging and photoregulation strategies have offered a possibility to real‐time sense and/or modulate specific cellular events in deep tissues with subcellular accuracy. Herein, the recent progress with respect to NIR light for monitoring and modulating the spatiotemporal dynamics of cell functions in living systems are summarized. In particular, the applications of NIR light‐based techniques in cancer theranostics, regenerative medicine, and neuroscience research are systematically introduced and discussed. In addition, the challenges and prospects for NIR light‐based cell sensing and regulating techniques are comprehensively discussed.

neurofibrillary tangles, and neuroinflammation, which progressively cause the loss of neurons and synaptic connectivity in the brain. [1,3-6] At present, AD is still incurable and existing treatments can only moderately relieve its symptoms. Current AD therapies, including anti-Aβ, anti-tau, and immune modulation, are only effective in preventing or delaying the development of AD in patients with very early pathology, but ineffective for slowing cognitive decline in patients who already have significant impairment. [1,6,7] The failures of these therapies are partly due to their inability to regenerate the lost neurons in the brains of symptomatic patients. Recently, stem cell-based regenerative therapy has shown great potential for AD treatment, given its ability to regenerate damaged neural networks in the brain by generating functional neural cells and integrating them into the existing synaptic network. [8-12] Moreover, several clinical trials have demonstrated the safety of stem cell-based therapies, [9,13] although they still face several challenges. First, the hostile environment in the AD brain adversely affects the survival and propagation of transplanted neural stem cells (NSCs), limiting effects to the short term. [9,14,15] Second, although NSCs are able to enhance synaptic connections through regenerating neurons, they do not have a strong ability to clear Aβ and Tau, and therefore cannot effectively treat the pathologies caused by their accumulation. [16] Third, due to the adverse pathological microenvironment of AD-particularly the high concentration of toxic Aβ oligomers-the neuronal differentiation of NSCs is inhibited, reducing neural regeneration in the brain. [16,17] Therefore, numerous efforts have been made to enhance the therapeutic capabilities (Aβ clearance and immune modulation) [1,7,16] and neuronal differentiation efficiency [18-20] of stem cells. Given the high complexity of AD pathobiology, multifunctional strategies that are capable of simultaneously managing multiple AD pathologies, including Aβ clearance and neural regeneration, are urgently needed. However, the development of such multifunctional therapies has yet to be achieved. Here, we report a multifunctional NSC therapy that simultaneously improves Aβ clearance and neural regeneration in an APPswe/PS1dE9 double transgenic mouse model (Figure 1). Alzheimer's disease (AD) is a common dementia that is currently incurable. The existing treatments can only moderately relieve the symptoms of AD to slow down its progress. How to achieve effective neural regeneration to ameliorate cognitive impairments is a major challenge for current AD treatment. Here, the therapeutic potential of a nanoformulation-mediated neural stem cell (NSC) therapy capable of simultaneous Aβ clearance and neural regeneration is investigated in a murine model. Genetically engineered NSCs capable of stably and continuously expressing neprilysin (NEP) are developed to enhance Aβ degradation and NSC survival in the brain. A PBAE-PLGA-Ag 2 S-RA-siSOX9 (PPAR-siSOX9)...

Effective drug delivery in the central nervous system (CNS) needs to have long blood-circulation halflives, to pass through the blood−brain barrier (BBB), and subsequently to be taken up by target cells. Herein, a traceable CNS delivery nanoformulation (RVG-NV-NPs) is developed by encapsulating bexarotene (Bex) and AgAuSe quantum dots (QDs) within Lamp2b-RVG-overexpressed neural stem cell (NSC) membranes. The highfidelity near-infrared-II imaging by AgAuSe QDs offers a possibility of in vivo monitoring the multiscale delivery process of the nanoformulation from the whole-body to the single-cell scale. It was revealed the synergy of acetylcholine receptor-targeting of RVG and the natural brain-homing and low immunogenicity of NSC membranes prolong the blood circulation, facilitate BBB crossing and nerve cell targeting of RVG-NV-NPs. Thus, in Alzheimer's disease (AD) mice, the intravenous delivery of as low as 0.5% of oral dose Bex showed highly effective up-regulation of the apolipoprotein E expression, resulting rapid alleviation of ∼40% β-amyloid (Aβ) level in the brain interstitial fluid after a single dose administration. The pathological progression of Aβ in AD mice is completely suppressed during a 1 month treatment, thus effectively protecting neurons from Aβ-induced apoptosis and maintaining the cognitive abilities of AD mice.