An O2 Self‐Supplementing and Reactive‐Oxygen‐Species‐Circulating Amplified Nanoplatform via H2O/H2O2 Splitting for Tumor Imaging and Photodynamic Therapy

Conventional photodynamic therapy (PDT) has limited applications in clinical cancer therapy due to the insufficient O₂ supply, inefficient reactive oxygen species (ROS) generation, and low penetration depth of light. In this work, a multifunctional nanoplatform, upconversion nanoparticles (UCNPs)@TiO₂@MnO₂ core/shell/sheet nanocomposites (UTMs), is designed and constructed to overcome these drawbacks by generating O₂ in situ, amplifying the content of singlet oxygen (¹O₂) and hydroxyl radical (?OH) via water‐splitting, and utilizing 980 nm near‐infrared (NIR) light to increase penetration depth. Once UTMs are accumulated at tumor site, intracellular H₂O₂ is catalyzed by MnO₂ nanosheets to generate O₂ for improving oxygen‐dependent PDT. Simultaneously, with the decomposition of MnO₂ nanosheets and 980 nm NIR irradiation, UCNPs can efficiently convert NIR to ultraviolet light to activate TiO₂ and generate toxic ROS for deep tumor therapy. In addition, UCNPs and decomposed Mn²⁺ can be used for further upconversion luminescence and magnetic resonance imaging in tumor site. Both in vitro and in vivo experiments demonstrate that this nanoplatform can significantly improve PDT efficiency with tumor imaging capability, which will find great potential in the fight against tumor.     

Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso‐Tetraphenyl porphine (TPP) for Photodynamic Therapy

The utilization of upconverting nanophosphors (UCNP) for photodynamic therapy (PDT) has gained significant interests due to its ability to convert deep‐penetrating near‐infra red (NIR) light (i.e., 978 nm) to visible light. Previous attempts to co‐localize UCNPs with photosensitizers suffer from low photo­sensitizer loading and problems with nanoparticle aggregation. Here, the preparation of a novel composite nanoparticle formulation comprising 100 nm β?NaYF₄:Yb³⁺,Er³⁺ UCNPs, and meso‐tetraphenyl porphine (TPP) photo­sensitizer, stabilized by biocompatible poly(ethylene glycol‐block‐(dl )lactic acid) block copolymers (PEG‐b‐PLA) is presented. A photosensitizer loading of 10 wt% with respect to UCNP crystal was achieved via the Flash NanoPrecipitation (FNP) process. A sterically stabilizing PEG layer on the composite nanoparticle surface prevents nanoparticle aggregation and ensures nanoparticle stability in water, PBS buffer, and culture medium containing serum proteins, resulting in nanoparticle suitable for in vivo applications. Based on in vitro studies utilizing HeLa cervical cancer cell lines, the composite nanoparticles are shown to exhibit low dark toxicity and efficient cancer cell‐killing activity upon NIR excitation. Exposure with 134 W cm^?2 of 978 nm light for 45 min resulted in 75% HeLa cell death. This is the first quantification of the cell‐killing capabilities of the UCNP/TPP composite nanoparticles formulated for photodynamic therapy.     

Remarkable NIR Enhancement of Multifunctional Nanoprobes for In Vivo Trimodal Bioimaging and Upconversion Optical/T2‐Weighted MRI‐Guided Small Tumor Diagnosis

Effective nanoprobes and contrast agents are urgently sought for early‐stage cancer diagnosis. Upconversion nanoparticles (UCNPs) are considerable alternatives for bioimaging, cancer diagnosis, and therapy. Yb³⁺/Tm³⁺ co‐doping brings both emission and excitation wavelengths into the near‐infrared (NIR) region, which is known as “optical transmission window” and ideally suitable for bioimaging. Here, NIR emission intensity is remarkably enhanced by 113 times with the increase of Yb³⁺ concentration from 20% to 98% in polyethylene glycol (PEG) modified NaYF₄:Yb³⁺/Tm³⁺ UCNPs. PEG‐UCNPs‐5 (98% Yb³⁺) can act as excellent nanoprobes and contrast agents for trimodal upconversion (UC) optical/CT/T₂‐weighted magnetic resonance imaging (MRI). In addition, the enhanced detection of lung in vivo long‐lasting tracking, as well as possible clearance mechanism and excretion routes of PEG‐UCNPs‐5 have been demonstrated. More significantly, a small tumor down to 4 mm is detected in vivo via intravenous injection of these nanoprobes under both UC optical and T₂‐weighted MRI modalities. PEG‐UCNPs‐5 can emerge as bioprobes for multi‐modal bioimaging, disease diagnosis, and therapy, especially the early‐stage tumor diagnosis.     

Neuroendocrine Tumor‐Targeted Upconversion Nanoparticle‐Based Micelles for Simultaneous NIR‐Controlled Combination Chemotherapy and Photodynamic Therapy,and Fluorescence Imaging

Although neuroendocrine tumors (NETs) are slow growing, they are frequently metastatic at the time of discovery and no longer amenable to curative surgery, emphasizing the need for the development of other treatments. In this study, multifunctional upconversion nanoparticle (UCNP)‐based theranostic micelles are developed for NET‐targeted and near‐infrared (NIR)‐controlled combination chemotherapy and photodynamic therapy (PDT), and bioimaging. The theranostic micelle is formed by individual UCNP functionalized with light‐sensitive amphiphilic block copolymers poly(4,5‐dimethoxy‐2‐nitrobenzyl methacrylate)‐polyethylene glycol (PNBMA‐PEG) and Rose Bengal (RB) photosensitizers. A hydrophobic anticancer drug, AB3, is loaded into the micelles. The NIR‐activated UCNPs emit multiple luminescence bands, including UV, 540 nm, and 650 nm. The UV peaks overlap with the absorption peak of photocleavable hydrophobic PNBMA segments, triggering a rapid drug release due to the NIR‐induced hydrophobic‐to‐hydrophilic transition of the micelle core and thus enabling NIR‐controlled chemotherapy. RB molecules are activated via luminescence resonance energy transfer to generate ¹O₂ for NIR‐induced PDT. Meanwhile, the 650 nm emission allows for efficient fluorescence imaging. KE108, a true pansomatostatin nonapeptide, as an NET‐targeting ligand, drastically increases the tumoral uptake of the micelles. Intravenously injected AB3‐loaded UCNP‐based micelles conjugated with RB and KE108—enabling NET‐targeted combination chemotherapy and PDT—induce the best antitumor efficacy.     

A Novel Theranostic Nanoplatform Based on Pd@Pt‐PEG‐Ce6 for Enhanced Photodynamic Therapy by Modulating Tumor Hypoxia Microenvironment

Photodynamic therapy (PDT), which utilizes reactive oxygen species to kill cancer cells, has found wide applications in cancer treatment. However, the hypoxic nature of most solid tumors can severely restrict the efficiency of PDT. Meanwhile, the hydrophobicity and limited tumor selectivity of some photosensitizers also reduce their PDT efficacy. Herein, a photosensitizer‐Pd@Pt nanosystem (Pd@Pt‐PEG‐Ce6) is designed for highly efficient PDT by overcoming these limitations. In the nanofabrication, Pd@Pt nanoplates, exhibiting catalase‐like activity to decompose H₂O₂ to generate oxygen, are first modified with bifunctional PEG (SH‐PEG‐NH₂). Then the Pd@Pt‐PEG is further covalently conjugated with the photosensitizer chlorin e6 (Ce6) to get Pd@Pt‐PEG‐Ce6 nanocomposite. The Pd@Pt‐PEG‐Ce6 exhibits good biocompatibility, long blood circulation half‐life, efficient tumor accumulation, and outstanding imaging properties. Both in vitro and in vivo experimental results clearly indicate that Pd@Pt‐PEG‐Ce6 effectively delivers photosensitizers to cancer cells/tumor sites and triggers the decomposition of endogenous H₂O₂ to produce oxygen, resulting in a remarkably enhanced PDT efficacy. Moreover, the moderate photothermal effect of Pd@Pt nanoplates also strengthen the PDT of Pd@Pt‐PEG‐Ce6. Therefore, by integrating the merits of high tumor‐specific accumulation, hypoxia modulation function, and mild photothermal effect into a single nanoagent, Pd@Pt‐PEG‐Ce6 readily acts as an ideal nanotherapeutic platform for enhanced cancer PDT.     

Tumor Microenvironment‐Responsive Mesoporous MnO2‐Coated Upconversion Nanoplatform for Self‐Enhanced Tumor Theranostics

The insufficient blood flow and oxygen supply in solid tumor cause hypoxia, which leads to low sensitivity of tumorous cells and thus causing poor treatment outcome. Here, mesoporous manganese dioxide (mMnO₂) with ultrasensitive biodegradability in a tumor microenvironment (TME) is grown on upconversion photodynamic nanoparticles for not only TME‐enhanced bioimaging and drug release, but also for relieving tumor hypoxia, thereby markedly improving photodynamic therapy (PDT). In this nanoplatform, mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO₂) with covalently loaded chlorin e6 are obtained as near‐infrared light mediated PDT agents, and then a mMnO₂ shell is grown via a facile ultrasonic way. Because of its unique mesoporous structure, the obtained nanoplatform postmodified with polyethylene glycol can load the chemotherapeutic drug of doxorubicin (DOX). When used for antitumor application, the mMnO₂ degrades rapidly within the TME, releasing Mn²⁺ ions, which couple with trimodal (upconversion luminescence, computed tomography (CT), and magnetic resonance imaging) imaging of UCNPs to perform a self‐enhanced imaging. Significantly, the degradation of mMnO₂ shell brings an efficient DOX release, and relieve tumor hypoxia by simultaneously inducing decomposition of tumor endogenous H₂O₂ and reduction of glutathione, thus achieving a highly potent chemo‐photodynamic therapy.     

A New Single 808 nm NIR Light‐Induced Imaging‐Guided Multifunctional Cancer Therapy Platform

The NIR light‐induced imaging‐guided cancer therapy is a promising route in the targeting cancer therapy field. However, up to now, the existing single‐modality light‐induced imaging effects are not enough to meet the higher diagnosis requirement. Thus, the multifunctional cancer therapy platform with multimode light‐induced imaging effects is highly desirable. In this work, captopril stabilized‐Au nanoclusters Au₂₅(Capt)₁₈?(Au₂₅) are assembled into the mesoporous silica shell coating outside of Nd³⁺‐sensitized upconversion nanoparticles (UCNPs) for the first time. The newly formed Au₂₅ shell exhibits considerable photothermal effects, bringing about the photothermal imaging and photoacoustic imaging properties, which couple with the upconversion luminescence imaging. More importantly, the three light‐induced imaging effects can be simultaneously achieved by exciting with a single NIR light (808 nm), which is also the triggering factor for the photothermal and photodynamic cancer therapy. Besides, the nanoparticles can also present the magnetic resonance and computer tomography imaging effects due to the Gd³⁺ and Yb³⁺ ions in the UCNPs. Furthermore, due to the photodynamic and the photothermal effects, the nanoparticles possess efficient in vivo tumor growth inhibition under the single irradiation of 808 nm light. The multifunctional cancer therapy platform with multimode imaging effects realizes a true sense of light‐induced imaging‐guided cancer therapy.     

Highly Emissive Nd3+‐Sensitized Multilayered Upconversion Nanoparticles for Efficient 795 nm Operated Photodynamic Therapy

Photodynamic therapy (PDT) is a noninvasive and site‐specific therapeutic technique for the clinical treatment of various of superficial diseases. In order to tuning the operation wavelength and improve the tissue penetration of PDT, rare‐earth doped upconversion nanoparticles (UCNPs) with strong anti‐stokes emission are introduced in PDT recently. However, the conventional Yb³⁺‐sensitized UCNPs are excited at 980 nm which is overlapped with the absorption of water, thus resulting in strong overheating effect. Herein, a convenient but effective design to obtain highly emissive 795 nm excited Nd³⁺‐sensitized UCNPs (NaYF₄:Yb,Er@NaYF₄:Yb_0.1Nd_0.4@NaYF₄) is reported, which provides about six times enhanced upconversion luminescence, comparing with traditional UCNPs (NaYF₄:Yb,Er@NaYF₄). A colloidal stable and non‐leaking PDT nanoplatform is fabricated later through a highly PEGylated mesoporous silica layer with covalently linked photosensitizer (Rose Bengal derivative). With as‐prepared Nd³⁺‐sensitized UCNPs, the nanoplatform can produce singlet oxygen more effective than traditional UCNPs. Significant higher penetration depth and lower overheating are demonstrated as well. All these features make as‐prepared nanocomposites excellent platform for PDT treatment. In addition, the nanoplatform with uniform size, high surface area, and excellent colloidal stability can be extended for other biomedical applications, such as imaging probes, biosensors, and drug delivery vehicles.     

Modulation of Hypoxia in Solid Tumor Microenvironment with MnO2 Nanoparticles to Enhance Photodynamic Therapy

Hypoxia not only promotes tumor metastasis but also strengthens tumor resistance to therapies that demand the involvement of oxygen, such as radiation therapy and photodynamic therapy (PDT). Herein, taking advantage of the high reactivity of manganese dioxide (MnO₂) nanoparticles toward endogenous hydrogen peroxide (H₂O₂) within the tumor microenvironment to generate O₂, multifunctional chlorine e6 (Ce6) loaded MnO₂ nanoparticles with surface polyethylene glycol (PEG) modification (Ce6@MnO₂‐PEG) are formulated to achieve enhanced tumor‐specific PDT. In vitro studies under an oxygen‐deficient atmosphere uncover that Ce6@MnO₂‐PEG nanoparticles could effectively enhance the efficacy of light‐induced PDT due to the increased intracellular O₂ level benefited from the reaction between MnO₂ and H₂O₂, the latter of which is produced by cancer cells under the hypoxic condition. Owing to the efficient tumor homing of Ce6@MnO₂‐PEG nanoparticles upon intravenous injection as revealed by T1‐weighted magnetic resonance imaging, the intratumoral hypoxia is alleviated to a great extent. Thus, in vivo PDT with Ce6@MnO₂‐PEG nanoparticles even at a largely reduced dose offers remarkably improved therapeutic efficacy in inhibiting tumor growth compared to free Ce6. The results highlight the promise of modulating unfavorable tumor microenvironment with nanotechnology to overcome current limitations of cancer therapies.     

Glutathione‐Activatable and O2/Mn2+‐Evolving Nanocomposite for Highly Efficient and Selective Photodynamic and Gene‐Silencing Dual Therapy

Photodynamic therapy (PDT) has been applied in cancer treatment by converting O₂ into reactive singlet oxygen (¹O₂) to kill cancer cells. However, the effectiveness of PDT is limited by the fact that tumor hypoxia causes an inadequate O₂ supply, and the overexpressed glutathione (GSH) in cancer cells consumes reactive oxygen species. Herein, a multifunctional hybrid system is developed for selective and highly efficient PDT as well as gene‐silencing therapy using a novel GSH‐activatable and O₂/Mn²⁺‐evolving nanocomposite (GAOME NC). This system consists of honeycomb MnO₂ (hMnO₂) nanocarrier loaded with catalase, Ce6, and DNAzyme with folate label, which can specifically deliver payloads into cancer cells. Once endocytosed, hMnO₂ carriers are reduced by the overexpressed GSH to Mn²⁺ ions, resulting in the reduction of GSH level and disintegration of GAOME NC. The released catalases then trigger the breakdown of endogenous H₂O₂ to generate O₂, which is converted by the excited Ce6 into ¹O₂. The self‐sufficiency of O₂ and consumption of GSH effectively enhance the PDT efficacy. Moreover, DNAzyme is freed for gene silencing in the presence of self‐generated Mn²⁺ ions as cofactors. The rational synergy of enhanced PDT and gene‐silencing therapy remarkably improve the in vitro and in vivo therapeutic efficacy of cancers.     

NIR‐II Light Activated Photosensitizer with Aggregation‐Induced Emission for Precise and Efficient Two‐Photon Photodynamic Cancer Cell Ablation

Near infrared (NIR) light excitable photosensitizers are highly desirable for photodynamic therapy with deep penetration. Herein, a NIR‐II light (1200 nm) activated photosensitizer TQ‐BTPE is designed with aggregation‐induced singlet oxygen (¹O₂) generation for two‐photon photodynamic cancer cell ablation. TQ‐BTPE shows good two‐photon absorption and bright aggregation‐induced NIR‐I emission upon NIR‐II laser excitation. The ¹O₂ produced by TQ‐BTPE in an aqueous medium is much more efficient than that of commercial photosensitizer Ce6 under white light irradiation. Upon NIR‐II excitation, the two‐photon photosensitization of TQ‐BTPE is sevenfold higher than that of Ce6. The TQ‐BTPE molecules internalized by HeLa cells are mostly located in lysosomes as small aggregate dots with homogeneous distribution inside the cells, which favors efficient photodynamic cell ablation. The two‐photon photosensitization of TQ‐BTPE upon NIR‐I and NIR‐II excitation shows higher ¹O₂ generation efficiency than under NIR‐I excitation owing to the larger two‐photon absorption cross section at 920 nm. However, NIR‐II light exhibits better biological tissue penetration capability after passing through a fresh pork tissue, which facilitates stronger two‐photon photosensitization and better cancer cell ablation performance. This work highlights the promise of NIR‐II light excitable photosensitizers for deep‐tissue photodynamic therapy.     

Solution‐Processable Near‐Infrared–Responsive Composite of Perovskite Nanowires and Photon‐Upconversion Nanoparticles

Organolead halide perovskites (OHPs) have shown unprecedented potentials in optoelectronics. However, the inherent large bandgap has restrained its working wavelength within 280–800 nm, while light at other regions, e.g., near‐infrared (NIR), may cause drastic thermal heating effect that goes against the duration of OHP devices, if not properly exploited. Herein, a solution processable and large‐scale synthesis of multifunctional OHP composites containing lanthanide‐doped upconversion nanoparticles (UCNPs) is reported. Upon NIR illumination, the upconverted photons from UCNPs at 520–550 nm can be efficiently absorbed by closely surrounded OHP nanowires (NWs) and photocurrent is subsequently generated. The narrow full width at half maximum of the absorption of rare earth ions (Yb³⁺ and Er³⁺) has ensured high‐selective NIR response. Lifetime characterizations have suggested that Förster resonance energy transfer with an efficiency of 28.5% should be responsible for the direct energy transfer from UCNPs to OHP NWs. The fabricated proof‐of‐concept device has showcased perfect response to NIR light at 980 and 1532 nm, which has paved new avenues for applications of such composites in remote control, distance measurement, and stealth materials.     

Electrochromic Switch Devices Mixing Small‐ and Large‐Sized Upconverting Nanocrystals

The hasty progress in smart, portable, flexible, and transparent integrated electronics and optoelectronics is currently one of the driving forces in nanoscience and nanotechnology. A promising approach is the combination of transparent conducting electrode materials (e.g., silver nanowires, AgNWs) and upconverting nanoparticles (UCNPs). Here, electrochromic devices based on transparent nanocomposite films of poly(methyl methacrylate) and AgNWs covered by UCNPs of different sizes and compositions are developed. By combining the electrical control of the heat dissipation in AgNW networks with size‐dependent thermal properties of UCNPs, tunable electrochromic transparent devices covering a broad range of the chromatic diagrams are fabricated. As illustrative examples, devices mixing large‐sized (>70 nm) β‐NaYF₄:Yb,Ln and small‐sized (<15 nm) NaGdF₄:Yb,Ln@NaYF₄ core@shell UCNPs (Ln = Tm, Er, Ce/Ho) are presented, permitting to monitor the temperature‐dependent emission of the particles by the intensity ratio of the Er^{3+ 2}H_11/2 and ⁴S_3/2 → ⁴I_15/2 emission lines, while externally controlling the current flow in the AgNW network. Moreover, by defining a new thermometric parameter involving the intensity ratio of transitions of large‐ and small‐sized UCNPs, a relative thermal sensitivity of 5.88% K^?1 (at 339 K) is obtained, a sixfold improvement over the values reported so far.     

Fluorinated Polyethylenimine to Enable Transmucosal Delivery of Photosensitizer‐Conjugated Catalase for Photodynamic Therapy of Orthotopic Bladder Tumors Postintravesical Instillation

Photodynamic therapy (PDT) by insertion of an optical fiber into the bladder cavity has been applied in the clinic for noninvasive treatment of bladder tumors. To avoid systemic phototoxicity, bladder intravesical instillation of a photosensitizer may be an ideal approach for PDT treatment of bladder cancer, in comparison to conventional intravenous injection. However, the instillation‐based PDT for bladder cancer treatment remains to be less effective due to the poor urothelial uptake of photosensitizer, as well as the tumor hypoxia‐associated PDT resistance. Herein, it is uncovered that fluorinated polyethylenimine (F‐PEI) achieved by mixing with Chorin‐e6‐conjugated catalase (CAT‐Ce6) is able to form self‐assembled CAT‐Ce6/F‐PEI nanoparticles, which show greatly improved cross‐membrane, transmucosal, and intratumoral penetration capacities compared with CAT‐Ce6 alone or nonfluorinated CAT‐Ce6/PEI nanoparticles. Owing to the decomposition of tumor endogenous H₂O₂ by CAT‐Ce6/F‐PEI nanoparticles penetrating into bladder tumors, the tumor hypoxia would be effectively relieved to further favor PDT. Therefore, bladder intravesical instillation with CAT‐Ce6/F‐PEI nanoparticles could offer remarkably improved photodynamic therapeutic effect to destruct orthotopic bladder tumors with reduced systemic toxicity compared to hematoporphyrin, the first‐line photosensitizer used for bladder cancer PDT in clinic. This work presents a unique photosensitizer nanomedicine formulation, promising for clinical translation in instillation‐based PDT to treat bladder tumors.     

Photostable Iodinated Silica/Porphyrin Hybrid Nanoparticles with Heavy‐Atom Effect for Wide‐Field Photodynamic/Photothermal Therapy Using Single Light Source

Physical therapies including photodynamic therapy (PDT) and photothermal therapy (PTT) can be effective against diseases that are resistant to chemotherapy and remain as incurable malignancies (for example, multiple myeloma). In this study, to enhance the treatment efficacy for multiple myeloma using the synergetic effect brought about by combining PDT and PTT, iodinated silica/porphyrin hybrid nanoparticles (ISP HNPs) with high photostability are developed. They can generate both ¹O₂ and heat with irradiation from a light‐emitting diode (LED), acting as photosensitizers for PDT/PTT combination treatment. ISP HNPs exhibit the external heavy atom effect, which significantly improves both the quantum yield for ¹O₂ generation and the light‐to‐heat conversion efficiency. The in vivo fluorescence imaging demonstrates that ISP HNPs, modified with folic acid and polyethylene glycol (FA‐PEG‐ISP HNPs), locally accumulate in the tumor after 18 h of their intravenous injection into tumor‐bearing mice. The LED irradiation on the tumor area of the mice injected with FA‐PEG‐ISP HNPs causes necrosis of the tumor tissues, resulting in the inhibition of tumor growth and an improvement in the survival rate.     

Effectively Utilizing NIR Light Using Direct Electron Injection from Up‐Conversion Nanoparticles to the TiO2 Photoanode in Dye‐Sensitized Solar Cells

TiO₂/NaYF₄:Yb³⁺,Er³⁺ nano‐heterostructures are prepared in situ on the TiO₂ photoanode of dye‐sensitized solar cells (DSCs). Transmission electron microscopy (TEM) and high‐resolution (HR)‐TEM confirm the formation of TiO₂/NaYF₄:Yb³⁺,Er³⁺ nano‐heterostructures. The up‐converted fluorescence spectrum of the photoanode containing the nano‐heterostructure confirms electron injection from NaYF₄:Yb³⁺,Er³⁺ to the condution band (CB) of TiO₂. When using a photoanode containing the nano‐heterostructure in a DSC, the overall efficiency (η) of the device is 17% higher than that of a device without the up‐conversion nanoparticles (UCNPs) and 13% higher than that of a device containing mixed TiO₂ and UCNPs. Nano‐heterostructures of TiO₂/NaYF₄:Yb³⁺,Tm³⁺ and TiO₂/NaYF₄:Yb³⁺,Ho³⁺ can also be prepared in situ on TiO₂ photoanodes. The overall efficiency of the device containing TiO₂/NaYF₄:Yb³⁺,Ho³⁺ nano‐heterostructures is 15% higher than the control device without UCNPs. When nano‐heterostructures of TiO₂/NaYF₄:Yb³⁺,Tm³⁺ are used, the open‐circuit voltage (V_oc) and the short‐circuit current density (J_sc) are all slightly decreased. The effect of the different UCNPs results from the different energy levels of Er³⁺, Tm³⁺, and Ho³⁺. These results demonstrate that utilizing the UCNPs with the apporpriate energy levels can lead to effective electron injection from the UCNPs to the CB of TiO₂, effectively improving the photocurrent and overall efficiency of DSCs while using NIR light.     

Linear Chimeric Triblock Molecules Self‐Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo‐Photodynamic Therapy of Breast Cancer

Although nanoparticles are expected to revolutionize cancer treatment, their low efficacy remains the greatest limiting factor. Recent investigations found that nanoparticles' golden principle, the enhanced permeability and retention (EPR) effect, is limited by the complicated tumor microenvironment. Herein, novel transformable nanomaterials are designed to utilize the EPR effect more effectively. By tandem conjugation of the hydrophobic head (chlorin e6 (Ce6) or bilirubin (BR)), peptide to form hydrogen bond (Phe‐Phe‐Val‐Leu‐Lys (FFVLK)), and hydrophilic tail (polyethylene glycol (PEG)), chimeric molecules that can form micelles (Ce6/BR‐FFVLK‐PEG) in aqueous solution are synthesized. Notably, the spherical micelles retain shape transformability. After circulation and distribution, they respond to 650 nm laser irradiation, and morphologically change into nanofibers so as to facilitate their retention markedly inside the tumor. Upon loading a reactive oxygen species‐responsive paclitaxel dimer with thioketal linker (PTX₂‐TK), the resultant PTX₂‐TK@Ce6/BR‐FFVLK‐PEG nanomedicine serves as a potent chemo‐photodynamic therapeutic for cancer treatment. Evaluations at both cell level and animal level reveal that PTX₂‐TK@Ce6/BR‐FFVLK‐PEG exhibits superior biocompatibility and biodistribution, and suppresses 82.6% of in vitro cell growth and 61.8% of in vivo tumor growth at a common dose of intravenous injection (10 mg kg^?1 PTX and 3.3 mg kg^?1 Ce6), becoming a novel nanomedicine with extraordinary potential in cancer therapy.     

Poly(Acrylic Acid) Modification of Nd3+‐Sensitized Upconversion Nanophosphors for Highly Efficient UCL Imaging and pH‐Responsive Drug Delivery

In this work, a simple method is demonstrated for the synthesis of multifunctional core–shell nanoparticles NaYF₄:Yb,Er@NaYF₄:Yb@NaNdF₄:Yb@NaYF₄:Yb@PAA (labeled as Er@Y@Nd@Y@PAA or UCNP@PAA), which contain a highly effective 808‐nm‐to‐visible UCNP core and a thin shell of poly(acrylic acid) (PAA) to achieve upconversion bioimaging and pH‐sensitive anticancer chemotherapy simultaneously. The core–shell Nd³⁺‐sensitized UCNPs are optimized by varying the shell number, core size, and host lattices. The final optimized Er@Y@Nd@Y nanoparticle composition shows a significantly improved upconversion luminescence intensity, that is, 12.8 times higher than Er@Y@Nd nanoparticles. After coating the nanocomposites with a thin layer of PAA, the resulting UCNP@PAA nanocomposite perform well as a pH‐responsive nanocarrier and show clear advantages over UCNP@mSiO₂, which are evidenced by in vitro/in vivo experiments. Histological analysis also reveals that no pathological changes or inflammatory responses occur in the heart, lungs, kidneys, liver, and spleen. In summary, this study presents a major step forward towards a new therapeutic and diagnostic treatment of tumors by using 808‐nm excited UCNPs to replace the traditional 980‐nm excitation.     

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.     

Precise Molecular Engineering of Photosensitizers with Aggregation‐Induced Emission over 800 nm for Photodynamic Therapy

Owing to efficient singlet oxygen (¹O₂) generation in aggregate state, photosensitizers (PSs) with aggregation‐induced emission (AIE) have attracted much research interests in photodynamic therapy (PDT). In addition to high ¹O₂ generation efficiency, strong molar absorption in long‐wavelength range and near‐infrared (NIR) emission are also highly desirable, but difficult to achieve for AIE PSs since the twisted structures in AIE moieties usually lead to absorption and emission in short‐wavelength range. In this contribution, through acceptor engineering, a new AIE PS of TBT is designed to show aggregation‐induced NIR emission centered at 810 nm, broad absorption in the range between 300 and 700 nm with a large molar absorption coefficient and a high ¹O₂ generation efficiency under white light irradiation. Further, donor engineering by attaching two branched flexible chains to TBT yielded TBTC8 , which circumvented the strong intermolecular interactions of TBT in nanoparticles (NPs), yielding TBTC8 NPs with optimized overall performance in ¹O₂ generation, absorption, and emission. Subsequent PDT results in both in vitro and in vivo studies indicate that TBTC8 NPs are promising candidates in practical application.