Gold Nanoframeworks with Mesopores for Raman–Photoacoustic Imaging and Photo‐Chemo Tumor Therapy in the Second Near‐Infrared Biowindow

Gold‐based nanostructures with tunable wavelength of localized surface plasmon resonance (LSPR) in the second near‐infrared (NIR‐II) biowindow receive increasing attention in phototheranostics. In view of limited progress on NIR‐II gold nanostructures, a particular liposome template‐guided route is explored to synthesize novel gold nanoframeworks (AuNFs) with large mesopores (≈40 nm) for multimodal imaging along with therapeutic robustness. The synthesized AuNFs exhibit strong absorbance in NIR‐II region, affording their capacity of NIR‐II photothermal therapy (PTT) and photoacoustic (PA) imaging for deep tumors. Functionalization of AuNFs with hyaluronic acid (HA) endows the targeting capacity for CD44‐overexpressed tumor cells while gatekeeping doxorubicin (DOX) loaded into mesopores. Conjugation of Raman reporter 4‐aminothiophenol (4‐ATP) onto AuNFs yields a surface‐enhanced Raman scattering (SERS) fingerprint for Raman spectroscopy/imaging. In vivo evaluation of HA‐4‐ATP‐AuNFs‐DOX on tumor‐bearing xenografts demonstrates its high efficacy in eradication of solid tumors in NIR‐II under PA–Raman dual image‐guided photo‐chemotherapy. Thus, current AuNFs offer versatile capabilities for phototheranostics.     

Enhanced Antitumor Efficacy by 808 nm Laser‐Induced Synergistic Photothermal and Photodynamic Therapy Based on a Indocyanine‐Green‐Attached W18O49 Nanostructure

A novel nanoplatform based on tungsten oxide (W₁₈O₄₉, WO) and indocyanine green (ICG) for dual‐modal photothermal therapy (PTT) and photodynamic therapy (PDT) has been successfully constructed. In this design, the hierarchical unique nanorod‐bundled W₁₈O₄₉ nanostructures play roles in being not only as an efficient photothermal agent for PTT but also as a potential nanovehicle for ICG molecules via electrostatic adsorption after modified with trimethylammonium groups on their surface. It is found that the ability of ICG to produce cytotoxic reactive oxygen species for PDT is well maintained after being attached on the WO, thus the as‐obtained WO@ICG can achieve a synergistic effect of combined PTT and PDT under single 808 nm near‐infrared (NIR) laser excitation. Notably, compared with PTT or PDT alone, the enhanced HeLa cells lethality of the 808 nm laser triggered dual‐modal therapy is observed. The in vivo animal experiments have shown that WO@ICG has effective solid tumor ablation effect with 808 nm NIR light irradiation, revealing the potential of these nanocomposites as a NIR‐mediated dual‐modal therapeutic platform for cancer treatment.     

Unprecedented “All‐in‐One” Lanthanide‐Doped Mesoporous Silica Frameworks for Fluorescence/MR Imaging and Combination of NIR Light Triggered Chemo‐Photodynamic Therapy of Tumors

Designing a single multifunctional nanoparticle that can simultaneously impart both diagnostic and therapeutic functions is considered to be a long‐lasting hurdle for biomedical researchers. Conventionally, a multifunctional nanoparticle can be constructed by integrating organic dyes/magnetic nanoparticles to impart diagnostic functions and anticancer drugs/photosensitizers to achieve therapeutic outcomes. These multicomponents systems usually suffer from severe photobleaching problems and cannot be activated by near‐infrared (NIR) light. Here, it is demonstrated that all‐in‐one lanthanide‐doped mesoporous silica frameworks (EuGdOx@MSF) loaded with an anticancer drug, doxorubicin (DOX) can facilitate simultaneous bimodal magnetic resonance (MR) imaging with approximately twofold higher T₁‐MR contrast as compared to the commercial Gd(III)‐DTPA complex and fluorescence imaging with excellent photostability. Upon a very low dose (130 mW cm^?2) of NIR light (980 nm) irradiation, the EuGdOx@MSF not only can sensitize formation of singlet oxygen (¹O₂) by itself but also can phototrigger the release of the DOX payload effectively to exert combined chemo‐photodynamic therapeutic (PDT) effects and destroy solid tumors in mice completely. It is also discovered for the first time that the EuGdOx@MSF‐mediated PDT effect can suppress the level of the key drug resistant protein, i.e., p‐glycoprotein (p‐gp) and help alleviate the drug resistant problem commonly associated with many cancers.     

Ultrasmall Semiconducting Polymer Dots with Rapid Clearance for Second Near‐Infrared Photoacoustic Imaging and Photothermal Cancer Therapy

Phototheranostic agents in the second near‐infrared (NIR‐II) window (1000–1700 nm) are emerging as a promising theranostic platform for precision medicine due to enhanced penetration depth and minimized tissue exposure. The development of metabolizable NIR‐II nanoagents for imaging‐guided therapy are essential for noninvasive disease diagnosis and precise ablation of tumors. Herein, metabolizable highly absorbing NIR‐II conjugated polymer dots (Pdots) are reported for the first time for photoacoustic imaging guided photothermal therapy (PTT). The unique design of low‐bandgap D‐A π‐conjugated polymer (DPP‐BTzTD) together with modified nanoreprecipitation conditions allows to fabricate NIR‐II absorbing Pdots with ultrasmall (4 nm) particle size. Extensive experimental tests demonstrate that the constructed Pdots exhibit good biocompatibility, excellent photostability, bright photoacoustic signals, and high photothermal conversion efficiency (53%). In addition, upon tail‐vein intravenous injection of tumor‐bearing mice, Pdots also show high‐efficient tumor ablation capability with rapid excretion from the body. In particular, both in vitro and in vivo assays indicate that the Pdots possess remarkable PTT performance under irradiation with a 1064 nm laser with 0.5 W cm^?2, which is much lower than its maximum permissible exposure limit of 1 W cm^?2. This pilot study thus paves a novel avenue for the development of organic semiconducting nanoagents for future clinical translation.     

An Acceptor–Donor–Acceptor Structured Small Molecule for Effective NIR Triggered Dual Phototherapy of Cancer

Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is regarded as a more effective method for cancer treatment than single PDT or PTT. However, development of single component and near‐infrared (NIR) triggered agents for efficient dual phototherapy remains a challenge. Herein, a simple strategy to develop dual‐functional small‐molecules‐based photosensitizers for combined PDT and PTT treatment is proposed through: 1) finely modulating HOMO–LUMO energy levels to regulate the intersystem crossing (ISC) process for effective singlet oxygen (¹O₂) generation for PDT; 2) effectively inhibiting fluorescence via strong intramolecular charge transfer (ICT) to maximize the conversion of photo energy to heat for PTT or ISC process for PDT. An acceptor–donor–acceptor (A‐D‐A) structured small molecule (CPDT) is designed and synthesized. The biocompatible nanoparticles, FA‐CNPs, prepared by encapsulating CPDT directly with a folate functionalized amphipathic copolymer, present strong NIR absorption, robust photostability, cancer cell targeting, high photothermal conversion efficiency as well as efficient ¹O₂ generation under single 808 nm laser irradiation. Furthermore, synergistic PDT and PTT effects of FA‐CNPs in vivo are demonstrated by significant inhibition of tumor growth. The proposed strategy may provide a new approach to reasonably design and develop safe and efficient photosensitizers for dual phototherapy against cancer.     

PEGylated Micelle Nanoparticles Encapsulating a Non‐Fluorescent Near‐Infrared Organic Dye as a Safe and Highly‐Effective Photothermal Agent for In Vivo Cancer Therapy

Photothermal therapy (PTT), as a minimally invasive and highly effective cancer treatment approach, has received widespread attention in recent years. Tremendous effort has been devoted to explore various types of photothermal agents with high near‐infrared (NIR) absorbance for PTT cancer treatment. Despite many exciting progresses in the area, effective yet safe photothermal agents with good biocompatibility and biodegradability are still highly desired. In this work, a new organic PTT agent based on polyethylene glycol (PEG) coated micelle nanoparticles encapsulating a heptamethine indocyanine dye IR825 is developed, showing a strong NIR absorption band and a rather low quantum yield, for in vivo photothermal treatment of cancer. It is found that the IR825–PEG nanoparticles show ultra‐high in vivo tumor uptake after intravenous injection, and appear to be an excellent PTT agent for tumor ablation under a low‐power laser irradiation, without rendering any appreciable toxicity to the treated animals. Compared with inorganic nanomaterials and conjugated polymers being explored in PTT, the NIR‐absorbing micelle nanoparticles presented here may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications.     

One‐Pot Synthesis of Dual Stimulus‐Responsive Degradable Hollow Hybrid Nanoparticles for Image‐Guided Trimodal Therapy

Exploiting exogenous and endogenous stimulus‐responsive degradable nanoparticles as drug carriers can improve drug delivery systems (DDSs). The use of hollow nanoparticles may facilitate degradation, and combination of DDS with photodynamic therapy (PDT) and photothermal therapy (PTT) may enhance the anticancer effects of treatments. Here, a one‐pot synthetic method is presented for an anticancer drug (doxorubicin [DOX]) and photosensitizer‐containing hollow hybrid nanoparticles (HNPs) with a disulfide and siloxane framework formed in response to exogenous (light) and endogenous (intracellular glutathione [GSH]) stimuli. The hollow HNPs emit fluorescence within the near‐infrared window and allow for the detection of tumors in vivo by fluorescence imaging. Furthermore, the disulfides within the HNP framework are cleaved by intracellular GSH, deforming the HNPs. Light irradiation facilitates penetration of GSH into the HNP framework and leads to the collapse of the HNPs. As a result, DOX is released from the hollow HNPs. Additionally, the hollow HNPs generate singlet oxygen (¹O₂) and heat in response to light; thus, fluorescence imaging of tumors combined with trimodal therapy consisting of DDS, PDT, and PTT is feasible, resulting in superior therapeutic efficacy. Thus, this method may have several applications in imaging and therapeutics in the future.     

Biocompatible Nanoparticles Based on Diketo‐Pyrrolo‐Pyrrole (DPP) with Aggregation‐Induced Red/NIR Emission for In Vivo Two‐Photon Fluorescence Imaging

Compared with traditional one‐photon fluorescence imaging, two‐photon fluorescence imaging techniques have shown advantages such as increased penetration depth, lower tissue autofluorescence, and reduced photo­damage, and therefore are particularly useful for imaging tissues and animals. In this work, the design and synthesis of two novel DPP ‐based compounds with large two‐photon absorption (2PA) cross‐sections (σ ≥ 8100 GM) and aggregation‐induced emission (AIE) properties are reported. The new compounds are red/NIR emissive and show large Stokes shifts (Δλ ≥ 3571 cm^?1). 1,2‐Distearoyl‐sn‐glycero‐3‐phosphoethanol amine‐N‐[maleimide(polyethylene glycol)‐2000 (DSPE‐PEG‐Mal) is used as the encapsulation matrix to encapsulate DPP‐2 , followed by surface functionalization with cell penetrating peptide (CPP) to yield DPP‐2‐CPP nanoparticles with high brightness, good water dispersibility, and excellent biocompatibility. DPP‐2 nanoparticles have been used for cell imaging and two‐photon imaging with clear visualization of blood vasculature inside mouse ear skin with a depth up to 80 μm.     

Squaraine‐Doped Functional Nanoprobes: Lipophilically Protected Near‐Infrared Fluorescence for Bioimaging

Hydrophobically stabilized near‐IR fluorescence from self‐assembled nanoprobes composed of amphiphilic poly(maleic anhydride‐alt‐octadec‐1‐ene) (PMAO) and lipophilized squaraine dopants is reported. From comparative studies with varying lipophilicity of squaraine dyes as well as of nanoparticulate polymer matrices, it is found that dual protection by simultaneous lipophilization of the dye‐polymer pair greatly improves the chemical stability of labile squaraine dyes, to produce efficient NIR fluorescence in physiological aqueous milieux. The surface properties of negatively charged PMAO nanoparticles are readily modified by coating with an amine‐rich cationic glycol chitosan with biofunctionality. Efficient cellular imaging and in vivo sentinel lymph node mapping with size and surface‐controlled nanoprobes demonstrate that lipophilic dual protection of NIR fluorescence and the underlying functional nanoprobe approach hold great potential for bioimaging applications.     

Bismuth Ferrite‐Based Nanoplatform Design: An Ablation Mechanism Study of Solid Tumor and NIR‐Triggered Photothermal/Photodynamic Combination Cancer Therapy

Although nanomaterial‐mediated phototherapy, in particular photothermal therapy (PTT) and photodynamic therapy (PDT), is extensively investigated in recent years, the ablation mechanism, evolution, and rehabilitation process of in vivo solid tumor after phototherapy are rarely explored yet and remain a terra incognita. Herein, a kind of bismuth ferrite nanoparticles (abbreviated as BFO NPs) are strategically designed and synthesized with a desirable size and bioactivity as a brand‐new phototherapeutic agent for the phototherapy, which are of strong near infrared (NIR) absorbance, excellent biocompatibility, and outstanding photophysical activity for the hyperthemia and reactive oxygen species generation. Resultantly, BFO NPs can realize simultaneous PTT/PDT synergistic therapy outcome against cancer cells and solid tumor under NIR laser irradiation. Meanwhile, for the first time, more attentions are paid to demonstrate ablation mechanism and evolution process of in vivo solid tumor after phototherapy by B‐mode ultrasonography/magnetic resonance imaging as well as histopathological analysis, all of which verify a series of physiological processes, being in order of necrosis of parenchymal cells, in situ tissue disintegration, liquefaction, and finally encapsulation process.     

Molecular Imaging in the Second Near‐Infrared Window

In the past decade, noticeable progress has been achieved regarding fluorescence imaging in the second near‐infrared (NIR‐II) window. Fluorescence imaging in the NIR‐II window demonstrates superiorities of deep tissue penetration and high spatial and temporal resolution, which are beneficial for profiling physiological processes. Meanwhile, molecular imaging has emerged as an efficient tool to decipher biological activities on the molecular and cellular level. Extending molecular imaging into the NIR‐II window would enhance the imaging performance, providing more detailed and accurate information of the biological system. In this progress report, selected achievements made in NIR‐II molecular imaging are summarized. The organization of this report is based on strategies underlying rational designs of NIR‐II imaging probes, and their applications in molecular imaging are highlighted. This progress report may provide guidance and reference for further development of functional NIR‐II probes designed for high‐performance molecular imaging.     

Conjugated Polymer Based Nanoparticles as Dual‐Modal Probes for Targeted In Vivo Fluorescence and Magnetic Resonance Imaging

A facile strategy is developed to synthesize dual‐modal fluorescent‐magnetic nanoparticles (NPs) with surface folic acid by co‐encapsulation of a far‐red/near‐infrared (FR/NIR)‐emissive conjugated polymer (PFVBT) and lipid‐coated iron oxides (IOs) into a mixture of poly(lactic‐co‐glycolic‐acid)‐poly(ethylene glycol)‐folate (PLGA‐PEG‐FOL) and PLGA. The obtained NPs exhibit superparamagnetic properties and high fluorescence, which indicates that the lipid coated on IOs is effective at separating the conjugated polymer from IOs to minimize fluorescence quenching. These NPs are spherical in shape with an average diameter of ≈180 nm in water, as determined by laser light scattering. In vitro studies reveal that these dual‐modal NPs can serve as an effective fluorescent probe to achieve targeted imaging of MCF‐7 breast cancer cells without obvious cytotoxicity. In vivo fluorescence and magnetic resonance imaging results suggest that the NPs are able to preferentially accumulate in tumor tissues to allow dual‐modal detection of tumors in a living body. This demonstrates the potential of conjugated polymer based dual‐modal nanoprobes for versatile in vitro and in vivo applications in future.     

Mesoporous Silica Coated Single‐Walled Carbon Nanotubes as a Multifunctional Light‐Responsive Platform for Cancer Combination Therapy

The development of cancer combination therapies, many of which rely on nanoscale theranostic agents, has received increasing attention in recent years. In this work, polyethylene glycol (PEG) modified mesoporous silica (MS) coated single‐walled carbon nanotubes (SWNTs) are fabricated and utilized as a multifunctional platform for imaging guided combination therapy of cancer. A model chemotherapy drug, doxorubicin (DOX), could be loaded into the mesoporous structure of the obtained SWNT@MS‐PEG nano‐carriers with high efficiency. Upon stimulation under near‐infrared (NIR) light, photothermally triggered drug release from DOX loaded SWNT@MS‐PEG is observed inside cells, resulting in a synergistic cancer cell killing effect. As revealed by both photoacoustic (PA) and magnetic resonance (MR) imaging, we further uncover efficient tumor accumulation of SWNT@MS‐PEG/DOX after intravenous injection into mice. In vivo combination therapy using this agent is further demonstrated in a mouse tumor model, achieving a remarkable synergistic anti‐tumor effect superior to that obtained by mono‐therapy. Our work presents a new type of theranostic nano‐platform, which could load therapeutic molecules with high efficiency, be responsive to external NIR stimulation, and at the same time serve as a diagnostic imaging agent.     

A Near‐Infrared Light‐Triggered Nanocarrier with Reversible DNA Valves for Intracellular Controlled Release

A near‐infrared (NIR) light‐triggered nanocarrier is developed for intracellular controlled release with good stability, high nuclease resistance, and good biocompatibility. The nanocarrier consists of a gold nanorod core and mesoporous silica shell, capped with reversible single‐stranded DNA valves, which are manipulated by switching between the laser on/off states. Upon laser irradiation, the valves of the nanocarrier open and the cargo molecules can be released from the mesopores. When the NIR laser is turned off, the valves close and the nanocarrier stops releasing the cargo molecules. The release amount of the cargo molecules can be controlled precisely by adjusting the irradiation time and the laser on‐off cycles. Confocal fluorescence imaging shows that the nanocarrier can be triggered by the laser irradiation and the controlled release can be accomplished in living cells. Moreover, the therapeutic effect toward cancer cells can also be regulated when the chemotherapeutic drug doxorubicin is loaded into the nanocarrier. This novel approach provides an ideal platform for drug delivery by a NIR light‐activated mechanism with precise control of area, time, and especially dosage.     

An Integrated Multifunctional Nanoplatform for Deep‐Tissue Dual‐Mode Imaging

The combination of biocompatible superparamagnetic and photoluminescent nanoparticles (NPs) is intensively studied as highly promising multifunctional (magnetic confinement and targeting, imaging, etc.) tools in biomedical applications. However, most of these hybrid NPs exhibit low signal contrast and shallow tissue penetration for optical imaging due to tissue‐induced optical extinction and autofluorescence, since in many cases, their photoluminescent components emit in the visible spectral range. Yet, the search for multifunctional NPs suitable for high photoluminescence signal‐to‐noise ratio, deep‐tissue imaging is still ongoing. Herein, a biocompatible core/shell/shell sandwich structured Fe₃O₄@SiO₂@NaYF₄:Nd³⁺ nanoplatform possessing excellent superparamagnetic and near‐infrared (excitation) to near‐infrared (emission), i.e., NIR‐to‐NIR photoluminescence properties is developed. They can be rapidly magnetically confined, allowing the NIR photoluminescence signal to be detected through a tissue as thick as 13 mm, accompanied by high T₂ relaxivity in magnetic resonance imaging. The fact that both the excitation and emission wavelengths of these NPs are in the optically transparent biological windows, along with excellent photostability, fast magnetic response, significant T₂‐contrast enhancement, and negligible cytotoxicity, makes them extremely promising for use in high‐resolution, deep‐tissue dual‐mode (optical and magnetic resonance) in vivo imaging and magnetic‐driven applications.     

Semiconducting Nanocomposite with AIEgen‐Triggered Enhanced Photoluminescence and Photodegradation for Dual‐Modality Tumor Imaging and Therapy

Semiconducting polymer nanoparticles (SPNs) have potential in biological applications. While some SPNs have significant photothermal conversion efficiencies (PCEs) as photothermal and photoacoustic agents, other SPNs offer high fluorescence yields as photoluminescent agents. However, the energy balance distribution in SPNs inhibits their successful applications in photoluminescence/photoacoustic (PL/PA) dual‐modality imaging. Additionally, the ultrastability of SPNs in vivo may cause damage to organisms. This work reports nanocomposite semiconducting polymer and tetraphenylethene nanoparticles (STNPs) constructed by semiconducting polymers (SPs) and tetraphenylethene aggregation‐induced emission luminogens (TPE AIEgens). The SP SPC10 endows good photothermal conversion ability, and the AIEgen TPBM supports enhanced photoluminescence of the STNPs. The results show that the STNPs can act as PL/PA dual‐modality imaging agents. The signal‐to‐noise (S/N) ratio in the PL modality reaches 8.7, and the imaging depth in the PA modality is 5.8 mm. The SPC10 in the STNPs can be decomposed under 90 mW cm^?2 white light irradiation in 6 h without any other additional agents. Furthermore, the STNPs are sufficient for the treatment of xenograft 4T1 tumor‐bearing mice based on photothermal therapy. The nanocomposite STNPs achieve optimized dual‐modality PL/PA imaging and the AIEgen‐triggered in situ photodegradation of SPNs. These properties indicate the significant potential of STNPs in clinical diagnosis and noninvasive therapy.     

Ultrastable and Biocompatible NIR‐II Quantum Dots for Functional Bioimaging

Fluorescence bioimaging in the second near‐infrared spectral region (NIR‐II, 1000–1700 nm) can provide advantages of high spatial resolution and large penetration depth, due to low light scattering. However, NIR‐II fluorophores simultaneously possessing high brightness, good stability, and biocompatibility are very rare. Hydrophobic NIR‐II emissive PbS@CdS quantum dots (QDs) are surface‐functionalized, via a silica and amphiphilic polymer (Pluronic F‐127) dual‐layer coating method. The as‐synthesized PbS@CdS@SiO₂@F‐127 nanoparticles (NPs) are aqueously dispersible and possess a quantum yield of ≈5.79%, which is much larger than those of most existing NIR‐II fluorophores. Thanks to the dual‐layer protection, PbS@CdS@SiO₂@F‐127 NPs show excellent chemical stability in a wide range of pH values. The biocompatibility of PbS@CdS@SiO₂@F‐127 NPs is studied, and the results show that the toxicity of the NPs in vivo could be minimal. PbS@CdS@SiO₂@F‐127 NPs are then utilized for in vivo and real‐time NIR‐II fluorescence microscopic imaging of mouse brain. The architecture of blood vessels is visualized and the imaging depth reaches 950 µm. Furthermore, in vivo NIR‐II fluorescence imaging of gastrointestinal tract is achieved, by perfusing PbS@CdS@SiO₂@F‐127 NPs into mice at a rather low dosage. This work illustrates the potential of ultrastable, biocompatible, and bright NIR‐II QDs in biomedical and clinical applications, which require deep tissue imaging.     

Imaging‐Guided pH‐Sensitive Photodynamic Therapy Using Charge Reversible Upconversion Nanoparticles under Near‐Infrared Light

Photodynamic therapy (PDT) based on upconversion nanoparticles (UCNPs) can effectively destroy cancer cells under tissue‐penetrating near‐infrared light (NIR) light. Herein, we synthesize manganese (Mn²⁺)‐doped UCNPs with strong red light emission at ca. 660 nm under 980 nm NIR excitation to activate Chlorin e6 (Ce6), producing singlet oxygen (¹O₂) to kill cancer cells. A layer‐by‐layer (LbL) self‐assembly strategy is employed to load multiple layers of Ce6 conjugated polymers onto UCNPs via electrostatic interactions. UCNPs with two layers of Ce6 loading (UCNP@2xCe6) are found to be optimal in terms of Ce6 loading and ¹O₂ generation. By further coating UCNP@2xCe6 with an outer layer of charge‐reversible polymer containing dimethylmaleic acid (DMMA) groups and polyethylene glycol (PEG) chains, we obtain a UCNP@2xCe6‐DMMA‐PEG nanocomplex, the surface of which is negatively charged and PEG coated under pH 7.4; this could be converted to have a positively charged naked surface at pH 6.8, significantly enhancing cell internalization of nanoparticles and increasing in vitro NIR‐induced PDT efficacy. We then utilize the intrinsic optical and paramagnetic properties of Mn²⁺‐doped UCNPs for in vivo dual modal imaging, and uncover an enhanced retention of UCNP@2xCe6‐DMMA‐PEG inside the tumor after intratumoral injection, owing to the slightly acidic tumor microenvironment. Consequently, a significantly improved in vivo PDT therapeutic effect is achieved using our charge‐reversible UCNP@2xCe6‐DMMA‐PEG nanoparticles. Finally, we further demonstrate the remarkably enhanced tumor‐homing of these pH‐responsive charge‐switchable nanoparticles in comparison to a control counterpart without pH sensitivity after systemic intravenous injection. Our results suggest that UCNPs with finely designed surface coatings could serve as smart pH‐responsive PDT agents promising in cancer theranostics.     

Design and Synthesis of “All‐in‐One” Multifunctional FeS2 Nanoparticles for Magnetic Resonance and Near‐Infrared Imaging Guided Photothermal Therapy of Tumors

The ideal theranostic nanoplatform for tumors is a single nanoparticle that has a single semiconductor or metal component and contains all multimodel imaging and therapy abilities. The design and preparation of such a nanoparticle remains a serious challenge. Here, with FeS₂ as a model of a semiconductor, the tuning of vacancy concentrations for obtaining “all‐in‐one” type FeS₂ nanoparticles is reported. FeS₂ nanoparticles with size of ≈30 nm have decreased photoabsorption intensity from the visible to near‐infrared (NIR) region, due to a low S vacancy concentration. By tuning their shape/size and then enhancing the S vacancy concentration, the photoabsorption intensity of FeS₂ nanoparticles with size of ≈350 nm (FeS₂‐350) goes up with the increase of the wavelength from 550 to 950 nm, conferring the high NIR photothermal effect for thermal imaging. Furthermore, this nanoparticle has excellent magnetic properties for T₂‐weighted magnetic resonance imaging (MRI). Subsequently, FeS₂‐350 phosphate buffer saline (PBS) dispersion is injected into the tumor‐bearing mice. Under the irradiation of 915‐nm laser, the tumor can be ablated and the metastasis lesions in liver suffer significant inhibition. Therefore, FeS₂‐350 has great potential to be used as novel “all‐in‐one” multifunctional theranostic nanoagents for MRI and NIR dual‐modal imaging guided NIR‐photothermal ablation therapy (PAT) of tumors.     

Monitoring the Real‐Time Circulatory System‐Related Physiological and Pathological Processes In Vivo Using a Multifunctional NIR‐II Probe

The dysfunction of the circulatory system leads to various pathological processes with high morbidity. Recently, fluorescence imaging in the near‐infrared II (NIR‐II) window (1000–1700 nm) has attracted immense attention in many biological processes. The rapid metabolism and low toxicity of some NIR‐II organic small molecules indicate their feasibility for use in visualizing the circulatory system. However, most of the reported NIR‐II organic small molecules presently encounter such dilemmas as complicated synthetic procedures and low quantum yields (QY). To address this challenge, a series of facilely prepared NIR‐II organic small molecule CQ‐T (CQ‐1‐4T) are designed and these compounds are loaded with biocompatible human serum albumin (HSA) to improve QY. Among them, CQL (CQ‐4T/HSA) demonstrates superior optical properties and a 6.65‐fold increase in fluorescence compared to the small molecule alone. Further work validates the efficacy and accuracy of CQL in monitoring the real‐time circulatory system‐related physiological and pathological processes in vivo, including thrombosis, peripheral arterial disease, tumor angiogenesis, and lymphatic drainage. Moreover, the excellent optical properties of CQL enable precise tumor resection and sentinel lymph node biopsy under NIR‐II navigation. In conclusion, CQL is a novel and promising NIR‐II organic probe with multifunctional imaging capability. It is highly desirable to accelerate its future translations into the clinic.