Autocatalytic Delivery of Brain Tumor–Targeting,Size‐Shrinkable Nanoparticles for Treatment of Breast Cancer Brain Metastases

Breast cancer brain metastases (BCBMs) represent a major cause of morbidity and mortality among patients with breast cancer. Chemotherapy, which is widely used to treat tumors outside of the brain, is often ineffective on BCBMs due to its inability to efficiently cross the blood‐brain barrier (BBB). Although the BBB is partially disrupted in tumor lesions, it remains intact enough to prevent most therapeutics from entering the brain. Here, a nanotechnology approach is reported that can overcome the BBB through synthesis of lexiscan‐loaded, AMD3100‐conjugated, shrinkable nanoparticles (NPs), or LANPs. LANPs respond to neutrophil elastase–enriched tumor microenvironment by shrinking in size and disrupt the BBB in tumors through lexiscan‐mediated modulation. LANPs recognize tumor cells through the interaction between AMD3100 and CXCR4, which are expressed in metastatic tumor cells. The integration of tumor responsiveness, tumor targeting, and BBB penetration that enables LANPs to penetrate metastatic lesions in the brain with high efficiency is demonstrated and, when doxorubicin is encapsulated, LANPs effectively inhibit tumor growth and prolong the survival of tumor‐bearing mice. Due to their high efficiency in penetrating the BBB for BCBMs treatment, LANPs have the potential to be translated into clinical applications for improved treatment of patients with BCBMs.     

Two‐Step Targeted Hybrid Nanoconstructs Increase Brain Penetration and Efficacy of the Therapeutic Antibody Trastuzumab against Brain Metastasis of HER2‐Positive Breast Cancer

Therapeutic antibodies (e.g., trastuzumab, TRA) against human epidermal growth factor receptor 2 (HER2)‐positive breast cancers have shown benefits in controlling primary tumors, yet are ineffective against brain metastases due to their inability to cross the blood‐brain barrier (BBB). A novel hybrid nanoconstruct system is designed to deliver trastuzumab to brain metastasis of HER2‐positive breast cancer via a two‐step sequential targeting approach. Self‐assembly of a polysorbate 80 (PS 80)‐containing polymer, lipid, and polymer‐conjugated TRA forms hybrid nanoconstructs (TRA–terpolymer nanoparticles (TPN)) with high encapsulation efficiency and bioactivity. The PS 80 moiety enables the first‐step targeting and receptor‐mediated trancytosis across BBB is demonstrated in vitro with a 3D human BBB model in healthy and brain tumor‐bearing mice. The subsequent partial dissociation of the nanoconstructs exposes the encapsulated TRA for the second‐step targeting to HER2‐positive cancer cells in the brain. Intravenously injected TRA–TPN delivers 50‐fold TRA compared to free TRA to the brain metastasis of HER2‐positive breast cancer. Treatment with TRA–TPN increases tumor cell apoptosis by 4‐fold, inhibits tumor growth by 43‐fold, and prolongs median survival by >1.3‐fold compared to free TRA, without causing noticeable organ toxicity. These findings suggest the two‐step targeted nanoconstruct system is promising for shuttling therapeutic antibodies to treat central nervous system diseases.     

Biomimetic Nanocomposites Cloaked with Bioorthogonally Labeled Glioblastoma Cell Membrane for Targeted Multimodal Imaging of Brain Tumors

Brain tumor targeted delivery of diagnostic contrast agents has been an elusive goal due to the presence of the blood brain barrier (BBB) and the complex brain tumor microenvironment. Herein, an ingenious design of nanoscale contrast agents coated by bioorthogonally labeled brain tumor cell membrane for targeted diagnosis of glioblastoma through multiple complementary imaging modalities is presented. Taking advantage of bioorthogonal click reactions, an endothelial integrin receptor‐targeting peptide cRGD is decorated onto the nanocomposite surface to act in synergy with brain tumor cell membrane to offer BBB‐penetrating and homotypic targeting effect in the brain tumor microenvironment. Cellular and animal experimental results validate the superior targeting outcomes achieved by cRGD‐labeled brain tumor cell membrane coating. This study offers an example of a surface modified cell membrane as a potential theranostic strategy to overcome the delivery barriers in brain tumors.     

Multifunctional Photonics Nanoparticles for Crossing the Blood–Brain Barrier and Effecting Optically Trackable Brain Theranostics

Theranostic photonic nanoparticles (TPNs) that cross the blood–brain barrier (BBB) and efficiently deliver a therapeutic agent to treat brain diseases, simultaneously providing optical tracking of drug delivery and release, are introduced. These TPNs are constructed by physical encapsulation of visible and/or near‐infrared photonic molecules, in an ultrasmall micellar structure (<15 nm). Phytochemical curcumin is employed as a therapeutic as well as visible‐emitting photonic component. In vitro BBB model studies and animal imaging, as well as ex vivo examination, reveal that these TPNs are capable of transmigration across the BBB and subsequent accumulation near the orthotopic xenograft of glioblastoma multiforme (GBM) that is the most common and aggressive brain tumor whose vasculature retains permeability‐resistant properties. The intracranial delivery and release of curcumin can be visualized by imaging fluorescence produced by energy transfer from curcumin as the donor to the near‐infrared emitting dye, coloaded in TPN, where curcumin induced apoptosis of glioma cells. At an extremely low dose of TPN, a significant therapeutic outcome against GBM is demonstrated noninvasively by bioluminescence monitoring of time‐lapse proliferation of luciferase‐expressing U‐87 MG human GBM in the brain. This approach of TPN can be generally applied to a broad range of brain diseases.     

Theranostic USPIO‐Loaded Microbubbles for Mediating and Monitoring Blood‐Brain Barrier Permeation

Efficient and safe drug delivery across the blood‐brain barrier (BBB) remains one of the major challenges of biomedical and (nano‐) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)‐based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO‐MB are destroyed, resulting in acoustic forces inducing vessel permeability. At the same time, USPIO are released from the MB shell, they extravasate across the permeabilized BBB and they accumulate in extravascular brain tissue, thereby providing non‐invasive R ₂*‐based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R ₂* relaxometry are in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug fluorescein isothiocyanate (FITC)‐dextran into the brain. Such theranostic materials and methods are considered to be useful for mediating and monitoring drug delivery across the BBB and for enabling safe and efficient treatment of CNS disorders.     

Nanoparticles Surmounting Blood–Brain Tumor Barrier Through Both Transcellular and Paracellular Pathways to Target Brain Metastases

Brain metastases are one of the most difficult malignancies to treat owing to their location and mostly multifocal and infiltrative growth. Chemotherapy, which is often effective against tumors outside the brain, offers some hope for brain metastases. However, the efficacy of systemic drug delivery to brain metastases is extremely limited due largely to the blood–brain tumor barrier (BTB). Herein, it is reported that minoxidil‐loaded hyaluronic acid–tethered nanoparticles (M@H‐NPs) can efficiently and specially surmount the BTB through both transcellular and paracellular pathways and target brain metastases through coordination of hyaluronic acid with CD44 target. The transcellular endocytosis, paracellular claudin‐5 expression, and BTB crossing are evaluated to confirm that the developed M@H‐NPs can be endued with minoxidil's ability to boost transcytosis and downregulate tight junction protein in BTB endothelial cells at brain metastases for promoted BTB penetration. M@H‐NPs selectively deliver doxorubicin (DOX) to brain metastatic lesions, while sparing normal brain cells from harm. Treatment with M@H‐NPs/DOX significantly prolongs median survival of mice bearing brain metastases. Due to the fruitful BTB penetration and brain metastasis homing, and improved therapeutic outcome, the minoxidil‐based systemic drug delivery strategy may serve as a potential approach for clinical management of brain metastases.     

Photoacoustic Therapy for Precise Eradication of Glioblastoma with a Tumor Site Blood–Brain Barrier Permeability Upregulating Nanoparticle

Glioblastoma is an extremely difficult clinical indication with very few therapeutic choices. In this study, a nanoparticle is constructed featuring high red absorbance and selective penetration of the blood–brain barrier (BBB) at the tumor site. This nanoparticle can provide timely activation of the adenosine receptor on the BBB to allow self‐passage and accumulation in the tumor. The nanoparticle converts pulsed laser energy into a shockwave via photoacoustic (PA) cavitation to achieve localized mechanical damage and thus yields a precision antitumor effect. In addition to its therapeutic function, the nanoparticle‐mediated PA process can also generate images that provide valuable information regarding tumor depth, size, and vascular morphology to inform treatment planning and monitoring. The results show that the nanoparticles can be efficiently delivered into the glioblastoma via intravenous infusion and this PA shockwave therapy can selectively destroy glioblastoma tumors with no observable side effects on normal tissue.     

Multifunctional Shell–Core Nanoparticles for Treatment of Multidrug Resistance Hepatocellular Carcinoma

Multidrug resistance (MDR) is the main obstruction against the chemotherapy for hepatocellular carcinoma. Herein, a biodegradable multifunctional tumor‐targeted core–shell structural nanocarrier (RGD peptide functionalized nanoparticles, RGD‐NPs) is reported for treating MDR hepatocellular carcinoma, which consists of three components: pH‐triggered calcium phosphate shell, long circulation phosphatidylserine‐polyethylene glycol (PS‐PEG) core, and an active targeting ligand RGD peptide. Drug‐resistance inhibitor (verapamil, VER) and chemotherapeutic agent (mitoxantrone, MIT) are separately encapsulated into the outer shell layer and inner core layer to obtain VER and MIT loaded RGD‐NPs (VM‐RGD‐NPs). Due to the shell–core structure, the VER and MIT can release sequentially, thus synergistically weakening the efflux effect to MIT by MDR cells. Also, the calcium phosphate can trigger lysosomal escaping through the varied pH value. Together with the optimized internalization pathway in MDR tumor cells, the increased intracellular effective chemotherapeutic drug concentration can be realized, thus achieving the improved curative effect. In this system, the PEG extends the circulation time in vivo. Also, the peptide RGD distinctly increases the affinity to MDR tumors with respect to nontargeted nanoparticles. As a consequence, VM‐RGD‐NPs exhibit a significant synergistic effect toward the MDR hepatocellular carcinoma, providing a promising therapeutic approach for MDR tumor.     

A Yolk–Shell Nanoplatform for Gene‐Silencing‐Enhanced Photolytic Ablation of Cancer

Noninvasive near‐infrared (NIR) light responsive therapy is a promising cancer treatment modality; however, some inherent drawbacks of conventional phototherapy heavily restrict its application in clinic. Rather than producing heat or reactive oxygen species in conventional NIR treatment, here a multifunctional yolk–shell nanoplatform is proposed that is able to generate microbubbles to destruct cancer cells upon NIR laser irradiation. Besides, the therapeutic effect is highly improved through the coalition of small interfering RNA (siRNA), which is codelivered by the nanoplatform. In vitro experiments demonstrate that siRNA significantly inhibits expression of protective proteins and reduces the tolerance of cancer cells to bubble‐induced environmental damage. In this way, higher cytotoxicity is achieved by utilizing the yolk–shell nanoparticles than treated with the same nanoparticles missing siRNA under NIR laser irradiation. After surface modification with polyethylene glycol and transferrin, the yolk–shell nanoparticles can target tumors selectively, as demonstrated from the photoacoustic and ultrasonic imaging in vivo. The yolk–shell nanoplatform shows outstanding tumor regression with minimal side effects under NIR laser irradiation. Therefore, the multifunctional nanoparticles that combining bubble‐induced mechanical effect with RNA interference are expected to be an effective NIR light responsive oncotherapy.     

Antitumor Platelet‐Mimicking Magnetic Nanoparticles

Nanoparticles possess the potential to revolutionize cancer diagnosis and therapy. The ideal theranostic nanoplatform should own long system circulation and active cancer targeting. Additionally, it should be nontoxic and invisible to the immune system. Here, the authors fabricate an all‐in‐one nanoplatform possessed with these properties for personalized cancer theranostics. Platelet‐derived vesicles (PLT‐vesicles) along with their membrane proteins are collected from mice blood and then coated onto Fe₃O₄ magnetic nanoparticles (MNs). The resulting core–shell PLT‐MNs, which inherit the long circulation and cancer targeting capabilities from the PLT membrane shell and the magnetic and optical absorption properties from the MN core, are finally injected back into the donor mice for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Meanwhile, it is found that the PTT treatment impels PLT‐MNs targeting to the PTT sites (i.e., tumor sites), and exactly, in turn, the enhanced targeting of PLT‐MNs to tumor sites can improve the PTT effects. In addition, since the PLT membrane coating is obtained from the mice and finally injected into the same mice, PLT‐MNs exhibit stellar immune compatibility. The work presented here provides a new angle on the design of biomimetic nanoparticles for personalized diagnosis and therapy of various diseases.     

Self‐Assembled pH‐Sensitive Fluoromagnetic Nanotubes as Archetype System for Multimodal Imaging of Brain Cancer

Fluoromagnetic systems are recognized as an emerging class of materials with great potential in the biomedical field. Here, it is shown how to fabricate fluoromagnetic nanotubes that can serve as multimodal probes for the imaging and targeting of brain cancer. An ionic self‐assembly strategy is used to functionalize the surface of synthetic chrysotile nanotubes with pH‐sensitive fluorescent chromophores and ferromagnetic nanoparticles. The acquired magnetic properties permit their use as contrast agent for magnetic resonance imaging, and enable the tracking of tumor cell migration and infiltration responsible for metastatic growth and disease recurrence. Their organic component, changing its fluorescence attitude as a function of local pH, targets the cancer distinctive acidity, and allows localizing and monitoring the tumor occurrence and progression by mapping the acidic spatial distribution within biopsy tissues. The fluoromagnetic properties of nanotubes are preserved from the in vitro to the in vivo condition and they show the ability to migrate across the blood brain barrier, thus spontaneously reaching the brain tumor after injection. The simplicity of the synthesis route of these geomimetic nanomaterials combined with their demonstrated affinity with the in vivo condition strongly highlights their potential for developing effective functional materials for multimodal theranostics of brain cancer.     

Targeted Delivery of CRISPR/Cas9‐Mediated Cancer Gene Therapy via Liposome‐Templated Hydrogel Nanoparticles

Due to its simplicity, versatility, and high efficiency, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has emerged as one of the most promising approaches for treatment of a variety of genetic diseases, including human cancers. However, further translation of CRISPR/Cas9 for cancer gene therapy requires development of safe approaches for efficient, highly specific delivery of both Cas9 and single guide RNA to tumors. Here, novel core–shell nanostructure, liposome‐templated hydrogel nanoparticles (LHNPs) that are optimized for efficient codelivery of Cas9 protein and nucleic acids is reported. It is demonstrated that, when coupled with the minicircle DNA technology, LHNPs deliver CRISPR/Cas9 with efficiency greater than commercial agent Lipofectamine 2000 in cell culture and can be engineered for targeted inhibition of genes in tumors, including tumors the brain. When CRISPR/Cas9 targeting a model therapeutic gene, polo‐like kinase 1 (PLK1), is delivered, LHNPs effectively inhibit tumor growth and improve tumor‐bearing mouse survival. The results suggest LHNPs as versatile CRISPR/Cas9‐delivery tool that can be adapted for experimentally studying the biology of cancer as well as for clinically translating cancer gene therapy.     

Novel Au–SiO2–WO3 Core–Shell Composite Nanoparticles for Surface‐Enhanced Raman Spectroscopy with Potential Application in Cancer Cell Imaging

With the rapid development of nanotechnology during the last decades, the ability to detect and control individual objects at the nanoscale has enabled us to deal with complex biomedical challenges. In cancer imaging, novel nanoparticles (NPs) offer promising potential to identify single cancer cells and precisely label larger areas of cancer tissues. Herein, a new class of size tunable core–shell composite (Au–SiO₂–WO₃) nanoparticles is reported. These nanoparticles display an easily improvable ≈10³ surface‐enhanced Raman scattering (SERS) enhancement factor with a double Au shell for dried samples over Si wafers and several orders of magnitude for liquid samples. WO₃ core nanoparticles measuring 20–50 nm in diameter are sheathed by an intermediate 10–60 nm silica layer, produced by following the Stöber‐based process and Turkevich method, followed by a 5–20 nm thick Au outer shell. By attaching 4‐mercaptobenzoic acid (4‐MBA) molecules as Raman reporters to the Au, high‐resolution Raman maps that pinpoint the nanoparticles' location are obtained. The preliminary results confirm their advantageous SERS properties for single‐molecule detection, significant cell viability after 24 h and in vitro cell imaging using coherent anti‐stokes Raman scattering. The long‐term objective is to measure SERS nanoparticles in vivo using near‐infrared light.     

Molecular Probe Crossing Blood–Brain Barrier for Bimodal Imaging–Guided Photothermal/Photodynamic Therapies of Intracranial Glioblastoma

Currently, treatment of intracranial diseases still remains a great challenge because the blood–brain barrier (BBB) blocks access of most drugs to the central nervous system. Herein, a theranostic small molecular probe, iRGD‐ICG‐Lys‐DTPA@Gd (iRGD‐ILD), capable of crossing BBB is developed. Owing to the small molecular size and α_vβ₃ integrin receptor–mediated transcytosis, this tailor‐made molecular probe integrating the fluorescence and magnetic resonance imaging functions effectively passes through BBB to target tumor cells even in the early stage of glioblastoma multiforme (GBM), thereby allowing a bimodal imaging–guided therapy of GBM. The reactive oxygen species and heat generated by the ICG moiety under the 808 nm laser irradiation exert photodynamic/photothermal therapeutic effects, which results in significantly inhibited tumor growth and prolonged median survival of C6‐Luc glioma‐bearing mice. Notably, the integration of FDA‐approved clinically available agents, e.g., ICG, DTPA and Gd, into a molecular probe may ensure desirable biocompatibility and biosafety for in vivo applications. Overall, the results highlight the potential of a water‐soluble small molecule as a novel theranostic probe for highly effective GBM treatment.     

Tumor‐Microenvironment‐Adaptive Nanoparticles Codeliver Paclitaxel and siRNA to Inhibit Growth and Lung Metastasis of Breast Cancer

Prolonged circulation, specific and effective uptake by tumor cells, and rapid intracellular drug release are three main factors for the drug delivery systems to win the battle against metastatic breast cancer. In this work, a tumor microenvironment‐adaptive nanoparticle co‐loading paclitaxel (PTX) and the anti‐metastasis siRNA targeting Twist is prepared. The nanoparticle consists of a pH‐sensitive core, a cationic shell, and a matrix metalloproteinase (MMP)‐cleavable polyethylene glycol (PEG) corona conjugated via a peptide linker. PEG will be cut away by MMPs at the tumor site, which endows the nanoparticle with smaller particle size and higher positive charge, leading to more efficient cellular uptake in tumor cells and higher intra‐tumor accumulation of both PTX and siRNA in the 4T1 tumor‐bearing mice models compared to the nanoparticles with irremovable PEG. In addition, acid‐triggered drug release in endo/lysosomes is achieved through the pH‐sensitive core. As a result, the MMP/pH dual‐sensitive nanoparticles significantly inhibit tumor growth and pulmonary metastasis. Therefore, this tumor‐microenvironment‐adaptive nanoparticle can be a promising codelivery vector for effective therapy of metastatic breast cancer due to simultaneously satisfying the requirements of long circulating time, efficient tumor cell targeting, and fast intracellular drug release.     

Acid‐Responsive Transferrin Dissociation and GLUT Mediated Exocytosis for Increased Blood–Brain Barrier Transcytosis and Programmed Glioma Targeting Delivery

Receptor mediated transcytosis (RMT) is a common mechanism used for nanotherapeutics to traverse the blood–brain barrier (BBB). However, the transcytosis of ligand modified nanoparticles via RMT is likely to be trapped within brain capillary endothelial cells due to the high binding affinity of ligand with receptors, which greatly reduces the amount of nanoparticles across BBB. Here, P‐aminophenyl‐α‐D‐mannopyranoside (MAN) decorated doxorubicin‐loaded dendrigraft poly‐l‐lysine with acid‐cleavable transferrin (Tf) coating outside (DD‐MCT) is proposed. The DD‐MCT is engineered to specifically recognize the Tf receptor (TfR) on the luminal side of BBB endothelium. Then the DD‐MCT undergoes an acid‐responsive cleavage of Tf, leading to the separation of MAN‐decorated DGL‐DOX (DD‐M) from the Tf–TfR complex in endo/lysosomes. The detached DD‐M is more prone to escape from endo/lysosomes and can further be exocytosed into brain parenchyma via the mediation of glucose transporter located on the abluminal endothelial membrane. Moreover, the DD‐M in brain parenchyma can target glioma cells. Significantly, the DD‐MCT enters into brain parenchyma in greater amounts, resulting in enhanced accumulation at glioma site and thus improved antiglioma therapeutic outcome. This strategy pioneers a new path for reducing the trapping of nanotherapeutics within BBB endothelium but increasing their transcytosis into brain parenchyma.     

Rational Design of Nanoparticles with Deep Tumor Penetration for Effective Treatment of Tumor Metastasis

The limited penetration of nanoparticles in primary tumors and metastases remains a great challenge for effective treatment of tumor metastasis. This review outlines the current approaches and summarizes the rational design of nanoparticles with deep tumor penetration capacity for anti‐metastasis treatment. There are two ways to achieve better tumor penetration; through rational regulation of the physicochemical properties of nanoparticles and through remodeling of the tumor microenvironment, including the tumor vasculature and stromal environment. Moreover, biomimetic strategies that integrate the advantages of nanoparticles and metastasis‐homing molecules during cancer cell metastasis are discussed. These efforts have led to promising results in facilitating intratumoral permeation of various nanoparticles to enhance antitumor effects. The considerations and some feasible future directions for deep tumor penetration strategies are proposed to improve tumor metastasis therapies.     

Multicore Liquid Perfluorocarbon‐Loaded Multimodal Nanoparticles for Stable Ultrasound and 19F MRI Applied to In Vivo Cell Tracking

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell‐labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described. The perfluorocarbon enables monitoring the nanoparticles with quantitative ¹⁹F magnetic resonance imaging, making these particles effective multimodal imaging agents. Unlike typical core–shell perfluorocarbon‐based ultrasound contrast agents, these nanoparticles have an atypical fractal internal structure. The nonvaporizing highly hydrophobic perfluorocarbon forms multiple cores within the polymeric matrix and is, surprisingly, hydrated with water, as determined from small‐angle neutron scattering and nuclear magnetic resonance spectroscopy. Finally, the nanoparticles are used to image therapeutic dendritic cells with ultrasound in vivo, as well as with ¹⁹F MRI and fluorescence imaging, demonstrating their potential for long‐term in vivo multimodal imaging.     

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.     

Core–Shell Nanoparticle Interface and Wetting Properties

Latex colloids are among the most promising materials for broad thin film applications due to their facile surface functionalization. Yet, the effect of these colloids on chemical film and wetting properties cannot be easily evaluated. At the nanoscale, core–shell particles can deform and coalesce during thermal annealing, yielding fine‐tuned physical properties. Two different core–shell systems (soft and rigid) with identical shells but with chemically different core polymers and core sizes are investigated. The core–shell nanoparticles (NPs) are probed during thermal annealing in order to investigate their behavior as a function of nanostructure size and rigidity. X‐ray scattering allows to follow the re‐arrangement of the NPs and the structural evolution in situ during annealing. Evaluation by real‐space imaging techniques reveals a disappearance of the structural integrity and a loss of NP boundaries. The possibility to fine‐tune the wettability by tuning the core–shell NPs morphology in thin films provides a facile template methodology for repellent surfaces.