Near‐Infrared‐Resonant Gold/Gold Sulfide Nanoparticles as a Photothermal Cancer Therapeutic Agent

The development and optimization of near‐infrared (NIR)‐absorbing nanoparticles for use as photothermal cancer therapeutic agents has been ongoing. This work exploits the properties of gold/gold sulfide NIR‐absorbing nanoparticles (≈35–55 nm) that provide higher absorption (98% absorption and 2% scattering for gold/gold sulfide versus 70% absorption and 30% scattering for gold/silica nanoshells) as well as potentially better tumor penetration. The ability to ablate tumor cells in vitro and efficacy for photothermal cancer therapy is demonstrated, and an in vivo model shows significantly increased long‐term, tumor‐free survival. Furthermore, enhanced circulation and biodistribution is observed in vivo. This class of NIR‐absorbing nanoparticles has the potential to improve upon photothermal tumor ablation for cancer therapy.     

Cancer‐Cell‐Phenotype‐Dependent Differential Intracellular Trafficking of Unconjugated Quantum Dots

A diverse array of nanoparticles, including quantum dots (QDs), metals, polymers, liposomes, and dendrimers, are being investigated as therapeutics and imaging agents in cancer diseases. However, the role of the cancer‐cell phenotype on the uptake and intracellular fate of nanoparticles in cancer cells remains poorly understood. Reported here is that differences in cancer‐cell phenotypes can lead to significant differences in intracellular sorting, trafficking, and localization of nanoparticles. Unconjugated anionic QDs demonstrate dramatically different intracellular profiles in three closely related human‐prostate‐cancer cells used in the investigation: PC3, PC3‐flu, and PC3‐PSMA. QDs demonstrate punctated intracellular localization throughout the cytoplasm in PC3 cells. In contrast, the nanoparticles localize mainly at a single juxtanuclear location (“dot‐of‐dots”) inside the perinuclear recycling compartment in PC3‐PSMA cells, where they co‐localize with transferrin and the prostate‐specific membrane antigen. The results indicate that nanoparticle sorting and transport is influenced by changes in cancer‐cell phenotype and can have significant implications in the design and engineering of nanoscale drug delivery and imaging systems for advanced tumors.     

Humidity‐Responsive Single‐Nanoparticle‐Layer Plasmonic Films

2D materials possess many interesting properties, and have shown great application potentials. In this work, the development of humidity‐responsive, 2D plasmonic nanostructures with switchable chromogenic properties upon wetting–dewetting transitions is reported. By exploiting DNA hybridization‐directed anchoring of gold nanoparticles (AuNPs) on substrates, a series of single‐nanoparticle‐layer (SNL) plasmonic films is fabricated. Due to the collective plasmonic responses in SNL, these ultrathin 2D films display rapid and reversible red‐blue color change upon the wetting–dewetting transition, suggesting that hydration‐induced microscopic plasmonic coupling between AuNPs is replicated in the macroscopic, centimeter‐scale films. It is also found that hydration finely tunes the electric field distribution between AuNPs in the SNL film, based on which responsive surface‐enhanced Raman scattering substrates with spatially homogeneous hot spots are developed. Thus it is expected that DNA‐mediated 2D SNL structures open new avenues for designing miniaturized plasmonic nanodevices with various applications.     

A Dual‐Responsive Mesoporous Silica Nanoparticle for Tumor‐Triggered Targeting Drug Delivery

A novel pH‐ and redox‐ dual‐responsive tumor‐triggered targeting mesoporous silica nanoparticle (TTTMSN) is designed as a drug carrier. The peptide RGDFFFFC is anchored on the surface of mesoporous silica nanoparticles via disulfide bonds, which are redox‐responsive, as a gatekeeper as well as a tumor‐targeting ligand. PEGylated technology is employed to protect the anchored peptide ligands. The peptide and monomethoxypolyethylene glycol (MPEG) with benzoic‐imine bond, which is pH‐sensitive, are then connected via “click” chemistry to obtain TTTMSN. In vitro cell research demonstrates that the targeting property of TTTMSN is switched off in normal tissues with neutral pH condition, and switched on in tumor tissues with acidic pH condition after removing the MPEG segment by hydrolysis of benzoic‐imine bond under acidic conditions. After deshielding of the MPEG segment, the drug‐loaded nanoparticles are easily taken up by tumor cells due to the exposed peptide targeting ligand, and subsequently the redox signal glutathione in tumor cells induces rapid drug release intracellularly after the cleavage of disulfide bond. This novel intelligent TTTMSN drug delivery system has great potential for cancer therapy.     

Nanoassembled Peptide Biosensors for Rapid Detection of Matrilysin Cancer Biomarker

Early detection of cancer is likely to be one of the most effective means of reducing the cancer mortality rate. Hence, simple and ultra‐quick methods for noninvasive detection of early‐stage tumors are highly sought‐after. In this study, a nanobiosensing platform with a rapid response time of nearly 30 s is introduced for the detection of matrilysin—the salivary gland cancer biomarker—with a limit of detection as low as 30 nm . This sensing platform is based on matrilysin‐digestible peptides that bridge gold nanoparticle (AuNPs) cores (≈30–50 nm) and carbon quantum dot (CDs) satellites (≈9 nm). A stepwise synthesis procedure is used for self‐assembly of AuNP‐peptide‐CDs, ensuring their long‐term stability. The AuNP‐peptide‐CDs produce ideal optical signals, with noticeable fluorescence quenching effects. Upon peptide cleavage by matrilysin, CDs leave the surface of AuNPs, resulting in ultra‐fast detectable violet and visible fluorescent signals.     

Bioinspired Diselenide‐Bridged Mesoporous Silica Nanoparticles for Dual‐Responsive Protein Delivery

Controlled delivery of protein therapeutics remains a challenge. Here, the inclusion of diselenide‐bond‐containing organosilica moieties into the framework of silica to fabricate biodegradable mesoporous silica nanoparticles (MSNs) with oxidative and redox dual‐responsiveness is reported. These diselenide‐bridged MSNs can encapsulate cytotoxic RNase A into the 8–10 nm internal pores via electrostatic interaction and release the payload via a matrix‐degradation controlled mechanism upon exposure to oxidative or redox conditions. After surface cloaking with cancer‐cell‐derived membrane fragments, these bioinspired RNase A‐loaded MSNs exhibit homologous targeting and immune‐invasion characteristics inherited from the source cancer cells. The efficient in vitro and in vivo anti‐cancer performance, which includes increased blood circulation time and enhanced tumor accumulation along with low toxicity, suggests that these cell‐membrane‐coated, dual‐responsive degradable MSNs represent a promising platform for the delivery of bio‐macromolecules such as protein and nucleic acid therapeutics.     

EGaIn‐Assisted Room‐Temperature Sintering of Silver Nanoparticles for Stretchable,Inkjet‐Printed,Thin‐Film Electronics

Coating inkjet‐printed traces of silver nanoparticle (AgNP) ink with a thin layer of eutectic gallium indium (EGaIn) increases the electrical conductivity by six‐orders of magnitude and significantly improves tolerance to tensile strain. This enhancement is achieved through a room‐temperature “sintering” process in which the liquid‐phase EGaIn alloy binds the AgNP particles (≈100 nm diameter) to form a continuous conductive trace. Ultrathin and hydrographically transferrable electronics are produced by printing traces with a composition of AgNP‐Ga‐In on a 5 µm‐thick temporary tattoo paper. The printed circuit is flexible enough to remain functional when deformed and can support strains above 80% with modest electromechanical coupling (gauge factor ≈1). These mechanically robust thin‐film circuits are well suited for transfer to highly curved and nondevelopable 3D surfaces as well as skin and other soft deformable substrates. In contrast to other stretchable tattoo‐like electronics, the low‐cost processing steps introduced here eliminate the need for cleanroom fabrication and instead requires only a commercial desktop printer. Most significantly, it enables functionalities like “electronic tattoos” and 3D hydrographic transfer that have not been previously reported with EGaIn or EGaIn‐based biphasic electronics.     

NIR‐II‐Excited Intravital Two‐Photon Microscopy Distinguishes Deep Cerebral and Tumor Vasculatures with an Ultrabright NIR‐I AIE Luminogen

Intravital fluorescence imaging of vasculature morphology and dynamics in the brain and in tumors with large penetration depth and high signal‐to‐background ratio (SBR) is highly desirable for the study and theranostics of vascular‐related diseases and cancers. Herein, a highly bright fluorophore (BTPETQ) with long‐wavelength absorption and aggregation‐induced near‐infrared (NIR) emission (maximum at ≈700 nm) is designed for intravital two‐photon fluorescence (2PF) imaging of a mouse brain and tumor vasculatures under NIR‐II light (1200 nm) excitation. BTPETQ dots fabricated via nanoprecipitation show uniform size of around 42 nm and a high quantum yield of 19 ± 1% in aqueous media. The 2PF imaging of the mouse brain vasculatures labeled by BTPETQ dots reveals a 3D blood vessel network with an ultradeep depth of 924 µm. In addition, BTPETQ dots show enhanced 2PF in tumor vasculatures due to their unique leaky structures, which facilitates the differentiation of normal blood vessels from tumor vessels with high SBR in deep tumor tissues. Moreover, the extravasation and accumulation of BTPETQ dots in deep tumor (more than 900 µm) is visualized under NIR‐II excitation. This study highlights the importance of developing NIR‐II light excitable efficient NIR fluorophores for in vivo deep tissue and high contrast tumor imaging.     

Virion‐Like Membrane‐Breaking Nanoparticles with Tumor‐Activated Cell‐and‐Tissue Dual‐Penetration Conquer Impermeable Cancer

Poor drug penetration into tumor cells and tissues is a worldwide difficulty in cancer therapy. A strategy is developed for virion‐like membrane‐breaking nanoparticles (MBNs) to smoothly accomplish tumor‐activated cell‐and‐tissue dual‐penetration for surmounting impermeable drug‐resistant cancer. Tailor‐made dendritic arginine‐rich peptide prodrugs are designed to mimic viral protein transduction domains and globular protein architectures. Attractively, these protein mimics self‐assemble into virion‐like nanoparticles in aqueous solution, having highly ordered secondary structure. Tumor‐specific acidity conditions would activate the membrane‐breaking ability of these virion‐like nanoparticles to perforate artificial and natural membrane systems. As expected, MBNs achieve highly efficient drug penetration into drug‐resistant human ovarian (SKOV3/R) cancer cells. Most importantly, the well‐organized MBNs can pass through endothelial/tumor cells and spread from one cell to another one. Intravenous injection of MBNs into nude mice bearing impermeable SKOV3/R tumors suggests that the MBNs can recognize the tumor tissue after prolonged blood circulation, evoke the membrane‐breaking function for robust transvascular extravasation, and penetrate into the deep tumor tissue. This work provides the first demonstration of sophisticated molecular and supramolecular engineering of virion‐like MBNs to realize the long‐awaited cell‐and‐tissue dual‐penetration, contributing to the development of a brand‐new avenue for dealing with incurable cancers.     

Development of Dual‐Pore Coexisting Branched Silica Nanoparticles for Efficient Gene–Chemo Cancer Therapy

Various strategies for combination therapy to overcome current limitations in cancer therapy have been actively investigated. Among them, simultaneous delivery of multiple drugs is a subject of high interest due to anticipated synergistic effect, but there have been difficulties in designing and developing effective nanomaterials for this purpose. In this work, dual‐pore coexisting hybrid porous silica nanoparticles are developed through Volmer–Weber growth pathway for efficient co‐delivery of gene and anticancer drug. Based on the different pore sizes (2–3 and 40–45 nm) and surface modifications of the core and branch domains, loading and controlled release of gene and drug are achieved by appropriate strategies for each environment. With excellent loading capacity and low cytotoxicity of the present platform, the combinational cancer therapy is successfully demonstrated against human cervical cancer cell line. Through a series of quantitative analyses, the excellent gene–chemo combinational therapeutic efficiency is successfully demonstrated. It is expected that the present nanoparticle will be applicable to various biomedical fields that require co‐delivery of small molecule and nucleic acid.     

A High‐Sensitivity and Low‐Power Theranostic Nanosystem for Cell SERS Imaging and Selectively Photothermal Therapy Using Anti‐EGFR‐Conjugated Reduced Graphene Oxide/Mesoporous Silica/AuNPs Nanosheets

A high‐sensitivity and low‐power theranostic nanosystem that combines with synergistic photothermal therapy and surface‐enhanced Raman scattering (SERS) mapping is constructed by mesoporous silica self‐assembly on the reduced graphene oxide (rGO) nanosheets with nanogap‐aligned gold nanoparticles (AuNPs) encapsulated and arranged inside the nanochannels of the mesoporous silica layer. Rhodamine 6G (R6G) as a Raman reporter is then encapsulated into the nanochannels and anti‐epidermal growth factor receptor (EGFR) is conjugated on the nanocomposite surface, defined as anti‐EGFR‐PEG‐rGO@CPSS‐Au‐R6G, where PEG is polyethylene glycol and CPSS is carbon porous silica nanosheets. SERS spectra results show that rGO@CPSS‐Au‐R6G enhances 5 × 10⁶ magnification of the Raman signals and thus can be applied in the noninvasive cell tracking. Furthermore, it displays high sensitivity (detection limits: 10^?8m R6G solution) due to the “hot spots” effects by the arrangements of AuNPs in the nanochannels of mesoporous silica. The highly selective targeting of overexpressing EGFR lung cancer cells (A549) is observed in the anti‐EGFR‐PEG‐rGO@CPSS‐Au‐R6G, in contrast to normal cells (MRC‐5). High photothermal therapy efficiency with a low power density (0.5 W cm^?2) of near‐infrared laser can be achieved because of the synergistic effect by conjugated AuNPs and rGO nanosheets. These results demonstrate that the anti‐EGFR‐PEG‐rGO@CPSS‐Au‐R6G is an excellent new theranostic nanosystem with cell targeting, cell tracking, and photothermal therapy capabilities.     

Probing Cell‐Type‐Specific Intracellular Nanoscale Barriers Using Size‐Tuned Quantum Dots

The compartmentalization of size‐tuned luminescent semiconductor nanocrystal quantum dots (QDs) in four distinctive cell lines, which would be representative of the most likely environmental exposure routes to nanoparticles in humans, is studied. The cells are fixed and permeabilized prior to the addition of the QDs, thus eliminating any cell‐membrane‐associated effects due to active QD uptake mechanisms or to specificity of signaling routes in different cell types, but leaving intact the putative physical subcellular barriers. All quantitative assays are performed using a high content analysis (HCA) platform, thereby obtaining robust data on large cell populations. While smaller QDs 2.1 nm in diameter enter the nuclei and localize to the nucleoli in all cell types, the rate and dynamics of their passage vary depending on the cell origin. As the QD size is increased to 4.4 nm, penetration into the cell is reduced but each cell line displays its own cutoff size thresholds reflecting cell‐type‐determined cytoplasmic and nuclear pore penetration specificity. These results give rise to important considerations regarding the differential compartmentalization and susceptibility of organs, tissues, and cells to nanoparticles, and may be of prime importance for biomedical imaging and drug‐delivery research employing nanoparticle‐based probes and systems.     

Immune Cell‐Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery

Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell‐mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer‐specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP‐PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti‐BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP‐PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP‐PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell–cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The “self‐powered” immune cell‐mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.     

A Novel Self‐Assembled Mitochondria‐Targeting Protein Nanoparticle Acting as Theranostic Platform for Cancer

Self‐assembled protein nanoparticles have attracted much attention in biomedicine because of their biocompatibility and biodegradability. Protein nanoparticles have become widely utilized as diagnostic or therapeutic agents for various cancers. However, there are no reports that protein nanoparticles can specifically target mitochondria. This targeting is desirable, since mitochondria are critical in the development of cancer cells. In this study, the discovery of a novel self‐assembled metal protein nanoparticle, designated GST‐MT‐3, is reported, which targets the mitochondria of cancer cells within 30 min in vitro and rapidly accumulates in tumors within 1 h in vivo. The nanoparticles chelate cobalt ions [GST‐MT‐3(Co²⁺)], which induces reactive oxygen species (ROS) production and reduces the mitochondrial membrane potential. These effects lead to antitumor activity in vivo. GST‐MT‐3(Co²⁺) with covalently conjugated paclitaxel synergistically suppress tumors and prolong survival. Importantly, the effective dosage of paclitaxel is 50‐fold lower than that utilized in standard chemotherapy (0.2 vs 10 mg kg^?1). To the best of the authors' knowledge, GST‐MT‐3 is the first reported protein nanoparticle that targets mitochondria. It has the potential to be an excellent platform for combination therapies.     

Responsive Assembly of Upconversion Nanoparticles for pH‐Activated and Near‐Infrared‐Triggered Photodynamic Therapy of Deep Tumors

Upconversion nanoparticle (UCNP)‐mediated photodynamic therapy has shown great effectiveness in increasing the tissue‐penetration depth of light to combat deep‐seated tumors. However, the inevitable phototoxicity to normal tissues resulting from the lack of tumor selectivity remains as a major challenge. Here, the development of tumor‐pH‐sensitive photodynamic nanoagents (PPNs) comprised of self‐assembled photosensitizers grafted pH‐responsive polymeric ligands and UCNPs is reported. Under neutral pH conditions, photosensitizers aggregated in the PPNs are self‐quenched; however, upon entry into a tumor microenvironment with lower pH, the PPNs not only exhibit enhanced tumor‐cell internalization due to charge reversal but also are further disassembled into well‐dispersed nanoparticles in the endo/lysosomes of tumor cells, enabling the efficient activation of photosensitizers. The results demonstrate the attractive properties of both UCNP‐mediated deep‐tissue penetration of light and high therapeutic selectivity in vitro and in vivo.     

Light‐Triggered Biomimetic Nanoerythrocyte for Tumor‐Targeted Lung Metastatic Combination Therapy of Malignant Melanoma

Red blood cell (RBC) membrane‐cloaked nanoparticles, reserving the intact cell membrane structure and membrane protein, can gain excellent cell‐specific functions such as long blood circulation and immune escape, providing a promising therapy nanoplatform for drug delivery. Herein, a novel RBC membrane biomimetic combination therapeutic system with tumor targeting ability is constructed by embedding bovine serum albumin (BSA) encapsulated with 1,2‐diaminocyclohexane‐platinum (II) (DACHPt) and indocyanine green (ICG) in the targeting peptide‐modified erythrocyte membrane (R‐RBC@BPtI) for enhancing tumor internalization and synergetic chemophototherapy. R‐RBC@BPtI displays excellent stability and high encapsulation efficiency with multiple cores enveloped in the membrane. Benefited from the stealth functionality and targeting modification of erythrocyte membranes, R‐RBC@BPtI can significantly promote tumor targeting and cellular uptake. Under the near‐infrared laser stimuli, R‐RBC@BPtI presents remarkable instability by singlet oxygen and heat‐mediated cleavage so as to trigger effective drug release, thereby achieving deep penetration and accumulation of DACHPt and ROS in the tumor site. Consequently, R‐RBC@BPtI with tumor‐specific targeting ability accomplishes remarkable ablation of tumors and suppressed lung metastasis in vivo by photothermal and chemotherapy combined ablation under phototriggering. This research provides a novel strategy of targeted biomimetic nanoplatforms for combined cancer chemotherapy–phototherapy.     

Layer‐by‐Layer Coated Gold Nanoparticles: Size‐Dependent Delivery of DNA into Cells

Because nanoparticles are finding uses in myriad biomedical applications, including the delivery of nucleic acids, a detailed knowledge of their interaction with the biological system is of utmost importance. Here the size‐dependent uptake of gold nanoparticles (AuNPs) (20, 30, 50 and 80 nm), coated with a layer‐by‐layer approach with nucleic acid and poly(ethylene imine) (PEI), into a variety of mammalian cell lines is studied. In contrast to other studies, the optimal particle diameter for cellular uptake is determined but also the number of therapeutic cargo molecules per cell. It is found that 20 nm AuNPs, with diameters of about 32 nm after the coating process and about 88 nm including the protein corona after incubation in cell culture medium, yield the highest number of nanoparticles and therapeutic DNA molecules per cell. Interestingly, PEI, which is known for its toxicity, can be applied at significantly higher concentrations than its IC₅₀ value, most likely because it is tightly bound to the AuNP surface and/or covered by a protein corona. These results are important for the future design of nanomaterials for the delivery of nucleic acids in two ways. They demonstrate that changes in the nanoparticle size can lead to significant differences in the number of therapeutic molecules delivered per cell, and they reveal that the toxicity of polyelectrolytes can be modulated by an appropriate binding to the nanoparticle surface.     

The Architecture and Function of Monoclonal Antibody‐Functionalized Mesoporous Silica Nanoparticles Loaded with Mifepristone: Repurposing Abortifacient for Cancer Metastatic Chemoprevention

The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion‐invasion to vascular intima. It is demonstrated that MIF‐loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE‐MSN‐M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay. The specific binding results in downregulation of the captured cells and drives them into G0/G1 phase primarily attributed to the effect of aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion between cancer cells and endothelial cells, suggesting the combined inhibition effects of aEpCAM and MIF on E‐selectin and ICAM‐1 expression. The functionalized nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit lung metastasis. The present proof‐of‐concept study shows that the aE‐MSN‐M can prevent cancer metastasis by restraining CTC activity and their adhesion‐invasion to vascular intima.     

Nanoparticle Cookies Derived from Metal‐Organic Frameworks: Controlled Synthesis and Application in Anode Materials for Lithium‐Ion Batteries

The capacity of anode materials plays a critical role in the performance of lithium‐ion batteries. Using the nanocrystals of oxygen‐free metal‐organic framework ZIF‐67 as precursor, a one‐step calcination approach toward the controlled synthesis of CoO nanoparticle cookies with excellent anodic performances is developed in this work. The CoO nanoparticle cookies feature highly porous structure composed of small CoO nanoparticles (≈12 nm in diameter) and nitrogen‐rich graphitic carbon matrix (≈18 at% in nitrogen content). Benefiting from such unique structure, the CoO nanoparticle cookies are capable of delivering superior specific capacity and cycling stability (1383 mA h g^?1 after 200 runs at 100 mA g^?1) over those of CoO and graphite.     

The Human In Vivo Biomolecule Corona onto PEGylated Liposomes: A Proof‐of‐Concept Clinical Study

The self‐assembled layered adsorption of proteins onto nanoparticle (NP) surfaces, once in contact with biological fluids, is termed the “protein corona” and it is gradually seen as a determinant factor for the overall biological behavior of NPs. Here, the previously unreported in vivo protein corona formed in human systemic circulation is described. The human‐derived protein corona formed onto PEGylated doxorubicin‐encapsulated liposomes (Caelyx) is thoroughly characterized following the recovery of liposomes from the blood circulation of ovarian carcinoma patients. In agreement with previous investigations in mice, the in vivo corona is found to be molecularly richer in comparison to its counterpart ex vivo corona. The intravenously infused liposomes are able to scavenge the blood pool and surface‐capture low‐molecular‐weight, low‐abundance plasma proteins that cannot be detected by conventional plasma proteomic analysis. This study describes the previously elusive or postulated formation of protein corona around nanoparticles in vivo in humans and illustrates that it can potentially be used as a novel tool to analyze the blood circulation proteome.