Nanocages Research Articles

Self-assembly of DNA-hyperbranched aggregates catalyzed by a dual-targets recognition probe for miRNAs SERS detection in single cells

MicroRNAs (miRNAs) are very important for the early diagnosis and prognosis of tumors. In this work, we achieved the simultaneous detection of microRNA-155 (miR-155) and microRNA-21 (miR-21) with a dual target recognition probe (DRP) based on the nonlinear hybridization chain reaction (HCR). The multi-branched DNA products, three-dimensional multi-hotspot DNA dendrimers (3DmhD) were used in the amplification of the target miRNAs signal. The DRP is constructed with a core of gold nanocages (AuNCs), modified by nucleic acid probes and labeled with Raman signaling molecules ROX and Cy3. Experiments demonstrated that DRP could activate the multi-branched DNA reaction and generate 3DmhD in the presence of miR-155 and miR-21, which can achieve effective amplification of miR-21 and miR-155. When Surface Enhanced Raman Scattering (SERS) analysis was performed on 3DmhD, the multi-hot spot effect of 3DmhD significantly enhanced the signals of ROX and Cy3, allowing ultra-sensitive detection of miR-21 and miR-155 in vitro. To our delight, DRP also exhibited sensitive specificity and significant signal amplification for intracellular miRNAs. These results revealed that DRP has the potential to screen tumor cells by analyzing the expression levels of intracellular miRNAs.

Thin Nano Cages with Limited Hollow Space for Ultrahigh Sulfur Loading Lithium-Sulfur Batteries.

Owning to its various advantages, the lithium-sulfur battery is one of the research hot spots for new energy storage systems. Diverse hollow structures with specific morphologies have been used as the sulfur host materials to adsorb or/and catalyze the polysulfides, and can in particular concurrently inhibit the volume expansion during electrochemical processes in lithium-sulfur batteries. However, hollow space with a large volume will restrict the performance of the cell under high sulfur area loading, which is a very important indicator for the practical applications of the lithium-sulfur battery. Here, we report a nano thin cage cobalt acid zinc (ZnCo2O4) with limited hollow space as the cathode catalyst for lithium-sulfur batteries, which greatly reduces the electrode volume occupied by the hollow structure. The hollow volume of these thin cages is much smaller than those of the normally reported hollow materials in the literatue. The electrochemical performance of lithium-sulfur batteries with ZnCo2O4 thin cages could greatly improve due to the unique structure and the synergistic adsorption/catalytic effect of Zn/Co sites, especially at an ultrahigh S area load. Under a high S loading of 8 mg cm-2, the cell could keep a reversible capacity of 600 mAh g-1 after 500 cycles. Even at a sulfur loading of 10 mg cm-2, the cell still releases a discharge capacity of 1000 mAh g-1 which is equivalent of an area capacity of 10 mAh cm-2. This work provides a feasible way to develop lithium sulfur batteries with a high area sulfur load. This idea provides a possible solution to develop a Li-S battery at high area S loading and move one step closer to the practical applications.

Synthesis and plasmonic tuning of gold and gold–silver nanoparticles

Plasmonic particles represent a rapidly developing material for nanotechnology. They are used in biomedicine as sensoric, diagnostic and therapeutic agents. Most theranostic applications exploit the unique optical properties of gold or hybrid nanoparticles in which visible or near-infrared light excites localized plasmon resonances. The review discusses the latest advances in the synthesis of the most popular and sought-after nanoparticles such as gold nanospheres, nanorods, nanoshells, nanocages and nanostars and also gold–silver nanorods and nanocuboids. The consideration is focused on the design principles of particle size, shape and structure, which provides for desired tuning of optical properties such as plasmon resonance wavelength and absorption and scattering cross-sections. The optimal parameters of the particles for the use in the photothermal and photodynamic therapy, surface-enhanced Raman scattering and catalysis are discussed. <br> The bibliography includes 294 references.

Investigation of the interaction of 5-fluorouracil anticancer drug connected to the pristine, titanium doped boron phosphide nanocage (B12P12) with adenine nucleobases: by density functional theory

The aims of this work, is to investigate the adsorption of 5-Fluorouracil drug connected to the pristine, Titanium doped boron phosphide nanocage (B12P12) with adenine nucleobases by using density functional theory (DFT). For this means at the first step, we considered different configurations for adsorbing (5-FU) on the surface of nanocluster and adenine, and then all considered models are optimized at the WB97XD/Lanl2DZ level of theory by Gaussian (09) software. From optimized structures, geometrical parameters involve bond length and bond angle, thermodynamic, atom in molecule (AIM), reduced density gradient (RDG), Uv-visible spectrum, HOMO-LUMO orbitals, density of states (DOS), and quantum parameters are calculated and all results are analyzed. The calculated results reveal that in the Ti doped B12P12 nano cage, the gap energy and global hardness of system decrease significantly, and so the conductivity and reactivity of system increase from original state. This property is favorable for making sensitive sensor for this drug. The adsorption energy and enthalpy values for all studied models are negative, which indicate that the absorption process and their thermodynamic stability are favorable. The RDG and AIM results confirm that the adsorption of 5-FU drug connected to the nanocage with adenine is non-covalent type. The computational results demonstrate that the pristine and Ti–doped B12P12 can be used as a suitable candidate for fabricating detector and absorber for 5-FU drug.

Gold Nanocage-Based Photothermal Ablation Facilitates In Situ Vaccination for Melanoma Therapy.

Cancer immunotherapy represents a medical breakthrough, but there are still many patients unable to benefit from it because of the low response rate. The immunosuppressive tumor microenvironment (TME) is the main barrier to immunotherapy. Alleviating intratumoral immunosuppression is critical for improving the immune therapeutic efficacy. This work developed an in situ vaccination strategy by using gold nanocage (AuNC)-based photothermal effect in combination with an adjuvant and PD-L1 suppressor. In specific, this therapeutic strategy included three components: AuNCs as an inducer for tumor antigen production via photothermal ablation, CpG oligodeoxynucleotides as an adjuvant to amplify immune responses, and JQ1 as a PD-L1 suppressor to inhibit an immune checkpoint. The results showed that the in situ vaccination efficiently activated dendritic cells and primed T cells and exhibited a high therapeutic efficacy in the melanoma-bearing mice. This therapeutic strategy can increase the infiltration of cytotoxic T lymphocytes, suppress the PD-L1 expression in the tumor, and repolarize tumor-associated macrophages from pro-tumor M2 to the anti-tumor M1 phenotype, thereby remodeling the TME via regulating the innate immune and adaptive immune responses.

Amplified Drug Delivery System with a Pair of Master Keys Triggering Precise Drug Release for Chemo-Photothermal Therapy.

A versatile drug delivery system (DDS) enabling highly effective and targeting oncotherapy has always been of great significance in medical research. In the development of a stimuli-responsive DDS, compared with a single-factor stimulation DDS, a multifactor activation DDS has higher therapeutic specificity between diseased and normal tissue, but there are challenges in drug-release efficiency and united targeting cancer therapy. Herein, a novel dual-microRNA (dual-miRNA)-mediated 1:N-amplified DDS is fabricated. The gold nanocage (AuNC) was synthesized and used as a carrier. A DNA bridge motif as a nanolock (DNA bridge nanolock) was designed and modified on the surface of AuNCs, which could seal the holes of AuNCs. Using the dual-miRNAs as a pair of master keys, through DNA strand migration and DNAzyme self-assembly, a cell endogenous substance Mg2+-dependent DNAzyme cyclic shear reaction could perform the function of the master keys to open multiple locks for the enhanced release of doxorubicin from the AuNCs. In addition, under near-infrared irradiation, via absorption of light and heat release, the AuNC is activated to perform the function of photothermal therapy. Thereby, the system achieves precise chemo-photothermal therapy. Using the in vitro and in vivo anti-tumor analysis, the DDS could be proved to present a novel design of enhanced and targeted drug-release system for highly effective cancer therapy.

Pt-embodiment ZIF-67-derived nanocage as enhanced immunoassay for infectious virus detection

A facile and general strategy has been employed to develop highly-active nanozyme for immunoassay purposes. The hollow nanostructure of the Co3O4 nanocages (NCs) was anchoring the platinum nanoparticles (PtNPs) enclosed by the exposed oxides framework nd formed PtNPs@Co3O4 NCs. The embodiment of PtNPs was considered an ideal hybrid nanozyme that efficiently catalyzed the oxidation of the substrate molecules with enhanced activity. The PtNPs@Co3O4 NCs were revisited and repurposed on showing its nanozyme's activity with optimization done for the immunoassay platform. The embodiment of 32.44% Pt in the hollow nanostructures demonstrated the highest signal-to-noise responses in the immunoassay. In addition, the stepwise analysis highlighted the enhancement factor of the nanocages' catalytic mechanism. Based on their catalytic activity, these nanocages have been demonstrated to enable sub-femtogram level biosensing of norovirus-like particles (NoV-LPs) with highly selective signals in the capture-detect immunoassay format. The detection limit of the prepared immunoassay achieved 33.52 viral NoV copies/mL of the detection limit, which is 321-folds lower magnitude of the commercial ELISA. This nanocage's enhanced synergic catalytic properties could have great potential applications, including catalysis, biological labeling, and bioassays.

Construction of binary assembled MOF-derived nanocages with dual-band microwave absorbing properties

It is challenging to prepare a binary assembled metal-organic framework (MOF) by anisotropic epitaxial growth method. Besides, nanocages (NCs) with hollow structures are often constructed to improve microwave absorbing abilities. Herein, we combine the selective epitaxial growth and hollow engineering technologies to fabricate hybrid MOF-derived NCs. Benefiting from the unique nanocage/porous structure, complementary magnetic/dielectric components and suitable impedance matching characteristics, the optimized absorber (CoNi/TiO2@PC-NCs) exhibits unique microwave absorbing properties. It is worth noting that the minimum reflection loss (RLmin) of the absorber reaches -65.3 dB, and the overall effective absorption bandwidth (EAB, RL < -10 dB) covers 15.1 GHz (2.9–18 GHz). The maximum EAB under a single thickness covers 4.4 GHz, displaying skipping dual-band coverages at both high and low frequencies. This work might provide a novel perspective for the synthesis of assembled MOF-derived absorbers.

MSOT-Guided Nanotheranostics for Synergistic Mild Photothermal Therapy and Chemotherapy to Boost Necroptosis/Apoptosis.

The development of nanotheranostics for precision imaging-guided regulated cell death-mediated synergistic tumor therapy is still challenging. Herein, a novel multifunctional nanotheranostic agent, iRGD-coated maleimide-poly(ethylene glycol)-poly(lactic acid/glycolic acid)-encapsulated hydrophobic gold nanocages (AuNCs) and hydrophilic epigallocatechin gallate (EGCG) (PAuE) is developed for multispectral optoacoustic tomography (MSOT)-guided photothermal therapy (PTT) and chemotherapy. The portions of necroptotic and apoptotic tumor cells were 52.9 and 5.4%, respectively, at 6 h post-incubation after the AuNC-induced mild PTT treatment, whereas they became 14.0 and 46.1% after 24 h, suggesting that the switch of the cell death pathway is a time-dependent process. Mild PTT facilitated the release of EGCG which induces the downregulation of hypoxia-inducible factor-1 (HIF-1α) expression to enhance apoptosis at a later stage, realizing a remarkable tumor growth inhibition in vivo. Moreover, RNA sequence analyses provided insights into the significant changes in genes related to the cross-talk between necroptosis and apoptosis pathways via PAuE upon laser irradiation. In addition, the biodistribution and metabolic pathways of PAuE have been successfully revealed by 3D MSOT. Taken together, this strategy of first combination of EGCG and AuNC-based photothermal agent via triggering necroptosis/apoptosis to downregulate HIF-1α expression in a tumor environment provides a new insight into anti-cancer therapy.

Spermine‐Responsive Intracellular Self‐Aggregation of Gold Nanocages for Enhanced Chemotherapy and Photothermal Therapy of Breast Cancer (Small 30/2022)

Spermine‐Responsive Intracellular Self‐Aggregation of Gold Nanocages for Enhanced Chemotherapy and Photothermal Therapy of Breast Cancer (Small 30/2022)

Stimuli-Responsive Gold Nanocages for Cancer Diagnosis and Treatment.

With advances in nanotechnology, various new drug delivery systems (DDSs) have emerged and played a key role in the diagnosis and treatment of cancers. Over the last two decades, gold nanocages (AuNCs) have been attracting considerable attention because of their outstanding properties. This review summarizes current advancements in endogenous, exogenous, and dual/multi-stimuli responsive AuNCs in drug delivery. This review focuses on the properties, clinical translation potential, and limitations of stimuli-responsive AuNCs for cancer diagnosis and treatment.

Spermine-Responsive Intracellular Self-Aggregation of Gold Nanocages for Enhanced Chemotherapy and Photothermal Therapy of Breast Cancer.

Improving the precise accumulation and retention of nanomedicines in tumor cells is one of the keys to effective therapy of tumors. Herein, supramolecular peptides capped Au nanocages (AuNCs) that may self-aggregate into micron-sized clusters intracellularly in response to spermine (SPM), leading to specific accumulation and retention of AuNCs in SPM-overexpressed tumor cells, are developed. In this design, polydopamine (PDA) is in situ coated on the surface of AuNCs with doxorubicin (DOX) encapsulated. A small peptide, Phe-Phe-Val-Leu-Lys (FFVLK), is conjugated with PDA via esterification, and cucurbit[7]uril (CB[7]) is threaded onto the N-terminal Phe via host-guest interactions. Once the supramolecular peptide (CB[7]-FFVLK) capped AuNCs are internalized in SPM-overexpressed breast cancer cells, CB[7] can be competitively removed from FFVLK by SPM, due to the much higher binding affinity between CB[7] and SPM than that between CB[7] and Phe, leading to exposure of free FFVLK, which can subsequently self-assemble and induce the aggregation of AuNCs to micron-sized clusters, resulting in the significantly enhanced accumulation and retention of DOX-loaded AuNCs in tumor cells. Under NIR laser irradiation, the enhanced photothermal conversion of AuNCs aggregates, together with photothermia-induced release of DOX leads to synergistic photothermal therapy and chemotherapy against breast cancer.

Preparation of NIR-Responsive Gold Nanocages as Efficient Carrier for Controlling Release of EGCG in Anticancer Application.

Hepatocellular carcinoma (HCC) is a type of cancer that has a restricted therapy option. Epigallocatechin gallate (EGCG) is one of the main biologically active ingredients in tea. A large number of studies have shown that EGCG has preventive and therapeutic effects on various tumors. In addition, the development of near-infrared (NIR)-responsive nano-platforms has been attracting cancer treatment. In this work, we designed and synthesized a strategy of gold nanocages (AuNCs) as an efficient carrier for controlling release of EGCG for anti-tumor to achieve the synergistic functions of NIR-response and inhibited tumor cell proliferation. The diameter of AuNCs is about 50 nm and has a hollow porous (8 nm) structure. Thermal imaging-graphic studies proved that the AuNCs-EGCG obtained have photothermal response to laser irradiation under near-infrared light and still maintain light stability after multiple cycles of laser irradiation. The resulted AuNCs-EGCG reduced the proliferation rate of HepG2 cells to 50% at 48 h. Western blot analysis showed that NIR-responsive AuNCs-EGCG can promote the expression of HepG2 cell apoptosis-related proteins HSP70, Cytochrome C, Caspase-9, Caspase-3, and Bax, while the expression of Bcl-2 is inhibited. Cell confocal microscopy analysis proved that AuNCs-EGCG irradiated by NIR significantly upregulates Caspase-3 by nearly 2-fold and downregulates Bcl-2 by nearly 0.33-fold, which is beneficial to promote HepG2 cell apoptosis. This study provides useful information for the NIR-responsive AuNCs-EGCG as a new type of nanomedicine for HCC.

Theoretical assessment of the solvent effect on the functionalization of Au32 and C60 nanocages with fluorouracil drug

We studied the interaction of 5-Fluorouracil (5-FU) with Au32 and C60 fullerene nanocage by Density Functional Theory (DFT). From its different active sites, 5-FU was approached to the gold surface. All geometrical and energetic parameters of the complexes were calculated with the B3LYP–D3 considering the implicit solvent effect. From the results, the interaction energy is determined −18.91 and − 6.23 (kcal/mol) for the Au32 and C60 respectively, which reveals that 5-FU tends to absorb stronger to the gold-fullerene rather than C60. The DFT-based results for interaction energy determination are validated against high-level quantum chemistry method. Our findings reveal also that the dispersion forces play important role in the interaction properties prediction. Electronics structures and molecular descriptors of energetically stable complexes are further evaluated. Finally, DFTB-MD simulation for considered complexes in aqueous solution and ambient conditions showed that 5-FU was attracted to the implicit water molecules and bound weakly to the gold nanocage surface while it holds its attached position in the 5-FU/C60 complex. The present finding demonstrates that both Au32 and C60 nanocages could not be functionalized with the 5-FU drug in a water environment at ambient conditions.

Immuno-modulating theranostic gold nanocages for the treatment of rheumatoid arthritis in vivo

The chronic autoimmune of rheumatoid arthritis (RA) usually results in inflammation of synovial joint, leading to pain, and destruction of cartilage and bone. Activated macrophages (M1 macrophages) actively take part in the RA pathogenesis, intensifying the inflammation and destruction of bone and cartilage. In this study, a nanoplatform was developed by grafting PEGylated folate acid (FA) and conjugating IL-4 onto gold nanocages (AuNCs), into the nanopores of which anti-inflammatory drug methylprednisolone (MP) was loaded. The IL-4@AuNCs conjugates (consisting of PEGylated FA, IL-4 and MP) effectively targeted the folate receptors overexpressed on M1 macrophage surface, down-regulating the expression of M1 marker and up-regulating the M2 markers. The expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β was significantly suppressed by the MP-AuNCs and IL-4@AuNCs both in vitro and in vivo. The AuNCs conjugates could act as a contrast agent for photoacoustic (PA) phantom and CT imaging. The therapeutic efficacy of different AuNCs conjugates on RA in a model of rat adjuvant-induced arthritis (AIA) was verified by ELISA, histological, and Western blot analyses, revealing the therapeutic potential through immune-modulatory function on macrophages with IL-4@AuNCs being the best and followed by MP-AuNCs.

Understanding the Impact of Wall Thickness on Thermal Stability of Silver–Gold Nanocages

Understanding the Impact of Wall Thickness on Thermal Stability of Silver–Gold Nanocages

Lactoferrin- and Dendrimer-Bearing Gold Nanocages for Stimulus-Free DNA Delivery to Prostate Cancer Cells.

BackgroundThe use of gene therapy to treat prostate cancer is hampered by the lack of effective nanocarriers that can selectively deliver therapeutic genes to cancer cells. To overcome this, we hypothesize that conjugating lactoferrin, a tumor-targeting ligand, and the diaminobutyric polypropylenimine dendrimer into gold nanocages, followed by complexation with a plasmid DNA, would enhance gene expression and anti-proliferation activity in prostate cancer cells without the use of external stimuli.MethodsNovel gold nanocages bearing lactoferrin and conjugated to diaminobutyric polypropylenimine dendrimer (AuNCs-DAB-Lf) were synthesized and characterized. Following complexation with a plasmid DNA, their gene expression, cellular uptake and anti-proliferative efficacies were evaluated on PC-3 prostate cancer cells.ResultsAuNCs-DAB-Lf was able to complex DNA at conjugate: DNA weight ratios 5:1 onwards. Gene expression was at its highest after treatment with AuNCs-DAB-Lf at a weight ratio of 10:1, as a result of a significant increase in DNA uptake mediated by the conjugate at that ratio in PC-3 cells. Consequently, the anti-proliferative activity of AuNCs-DAB-Lf-DNA encoding TNFα was significantly improved by up to 9-fold compared with DAB dendriplex encoding TNFα.ConclusionLactoferrin-bearing dendrimer-conjugated gold nanocages are highly promising gene delivery systems for the treatment of prostate cancer.

Mesoporous Ag–TiO2 based nanocage like structure as sensitive and recyclable low-cost SERS substrate for biosensing applications

We fabricated a porous Ag–TiO2 film with a nanocage (NC) like structure as a sensitive, recyclable, and low-cost SERS substrate using facile methods. The developed nanocage structure of TiO2 film was first coated on a glass plate by doctor-blade method, and then thin film of silver with an optimum thickness of 10 nm was deposited onto it using thermal evaporation method. The unique mesoporous cage-like structure of TiO2 film leads to the exceptional and non-uniform growth of Ag film. The developed Ag nanostructure is also porous, caps spherical in shape, and the average separation between two consecutive nanostructures is 10 nm. These closely decorated nanostructures of Ag produce hotspots by localising the incident electric field within the minimal volume. The unique nanocage structure of TiO2 film provides a larger effective surface area of adsorption to the analytes. Thus, the synergistic effects of Ag–TiO2 NC structure exhibit significant enhancement of 108 considering rhodamine-6g (R6G) molecule as a probe using a portable handheld Raman spectrometer. The amount of electromagnetic enhancement was further investigated by 3D FDTD simulation that matches well with the experiments. The recyclability of the developed SERS substrate was explored by placing the SERS substrate under UV illumination for 130 min. The enhanced photocatalytic activity of Ag–TiO2 NC SERS film degrades the dye molecules under UV radiation multiple times successively. Further, the Ag–TiO2 SERS substrate is highly sensitive to detect various concentrations of urea up to 1 mM covering the vital range of blood urea level. Thus, the optimised, low-cost, reusable SERS substrate can be used as level free biosensors for routine analysis of biomolecules in clinical applications.

Heterostructured CoP·CoMoP nanocages as advanced electrocatalysts for efficient hydrogen evolution over a wide pH range

A sustainable and environmental-friendly method to produce hydrogen with high purity is the electrochemical water splitting, but its commercialization is challenged due to lack of cost-effective electrocatalysts for hydrogen evolution reaction (HER) over a wide pH range. Herein, a series of CoP·xCoMoP heterostructured nanocages (NCs) were prepared via a dissolution-regrowth and subsequent phosphorization process using metal-organic frameworks (MOFs) as template. The three-dimensional (3D) architecture of CoP·xCoMoP is constituted by the heterostructured nanosheets composed with CoP and CoMoP phase. These noble-metal-free earth-abundant transition metal phosphide (TMP) catalysts show a pH-universal HER activity with high efficiency. Under the optimal atom ratio of Co and Mo (6:5), CoP·5CoMoP NC catalysts can deliver a current density of 10 mA cm−2 at the overpotential of 72 mV with a Tafel slope of 60.3 mV dec−1 in 1.0 M KOH solution. The same current output requires overpotential of 44 mV in 0.5 M H2SO4 solution and 151 mV in1.0 M phosphate buffered solution (PBS), respectively. The superior HER activity of CoP·5CoMoP NC catalysts can be comparable to or even better than most of noble metal-free HER electrocatalysts reported recently. In addition, CoP·5CoMoP NC catalysts also show a fairly high HER stability over a wide pH range, and their HER activity can be well kept without significant loss for long-term electrolysis. The 3D CoP·5CoMoP heterostructured catalysts hold promise as efficient and low-cost catalysts for water splitting devices over a wide pH range.

Photosensitizer-loaded gold nanocages for immunogenic phototherapy of aggressive melanoma

Malignant melanoma remains the life-threatening form of skin cancer with high mortality and poor prognosis. Thus, an ideal melanoma therapeutic strategy is of immediate importance which can remove the primary tumor, as well as inhibit the metastasis and recurrence. Here, we report the fabrication of adjuvant monophosphoryl lipid A (MPLA) lipid bilayer-enveloped and photosensitizer indocyanine green (ICG)-loaded gold nanocages (MLI-AuNCs) for immunogenic phototherapy of aggressive melanoma. Hollow porous AuNCs are used as carriers to deliver MPLA and ICG, and protect ICG from photodegradation. Both AuNCs and ICG absorb near infrared (NIR) light and can be applied in controllable NIR-triggered photothermal and photodynamic combination therapy (PTT/PDT) of melanoma. MLI-AuNCs coated by thermosensitive lipid bilayer exhibit uniform size, good biocompatibility and bioavailability with prominent tumor accumulation, which further improve the PTT/PDT efficacy. MLI-AuNCs under NIR irradiation not only destroy the primary tumor by PTT/PDT, but also elicit robust antitumor immune response with melanoma associated antigens and MPLA released in situ. The released antigens and MPLA subsequently enhance the recruitment and maturation of dendritic cells, which further activate the effector T cells to inhibit metastases and recurrence of melanoma. This immunomodulatory-boosted PTT/PDT nanoplatform provides a new opportunity for highly aggressive melanoma treatment. Statement of significanceAn ideal tumor therapeutic strategy not only can remove the primary tumor, but also inhibit metastasis and recurrence. Here, we introduced a versatile nanoplatform MLI-AuNCs for immunogenic phototherapy of aggressive melanoma. Adjuvant MPLA and photosensitizer ICG can be protected and co-delivered to the tumors by thermosensitive lipid-enveloped AuNCs. MLI-AuNCs exhibited prominent tumor accumulation ability and produced the potent PTT/PDT effect to destroy the primary tumors with a single dose of NIR irradiation, as well as elicited the strong antitumor immunity to inhibit the metastasis and relapse. This study may provide a potential therapeutic vaccination strategy against advanced melanoma and other difficult-to-treat cancers.