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.     

Leveraging β-Adrenergic Receptor Signaling Blockade for Improved Cancer Immunotherapy Through Biomimetic Nanovaccine

The establishment of effective antitumor immune responses of vaccines is mainly limited by insufficient priming tumor infiltration of T cells and immunosuppressive tumor microenvironment (TME). Targeting β-adrenergic receptor (β-AR) signaling exerts promising benefits on reversing the suppressive effects directly on T cells, but it appears to have considerably limited antitumor performance when combined with vaccine-based immunotherapies. Herein, a tumor membrane-coated nanoplatform for codelivery of adjuvant CpG and propranolol (Pro), a β-AR inhibitor is designed. The biomimetic nanovaccine displayed an improved accumulation in lymph nodes and sufficient drug release, thereby inducing dendritic cell maturation and antigen presentation. Meanwhile, the integration of vaccination and blockade of β-AR signaling not only promoted the priming of the naive CD8+ T cells and effector T cell egress from lymph nodes, but also alleviated the immunosuppressive TME by decreasing the frequency of immunosuppressive cells and increasing the tumor infiltration of B cells and NK cells. Consequently, the biomimetic nanovaccines outperformed greater prophylactic and therapeutic efficacy than nanovaccines without Pro encapsulation in B16-F10 melanoma mice. Taken together, the work explored a biomimetic nanovaccine for priming tumor infiltration of T cells and immunosuppressive TME regulation, offering tremendous potential for a combined β-AR signaling-targeting strategy in cancer immunotherapy.     

Dynamically PEGylated and Borate‐Coordination‐Polymer‐Coated Polydopamine Nanoparticles for Synergetic Tumor‐Targeted,Chemo‐Photothermal Combination Therapy

Multifunctional nanomaterials with efficient tumor‐targeting and high antitumor activity are highly anticipated in the field of cancer therapy. In this work, a synergetic tumor‐targeted, chemo‐photothermal combined therapeutic nanoplatform based on a dynamically PEGylated, borate‐coordination‐polymer‐coated polydopamine nanoparticle (PDA@CP‐PEG) is developed. PEGylation on the multifunctional nanoparticles is dynamically achieved via the reversible covalent interaction between the surface phenylboronic acid (PBA) group and a catechol‐containing poly(ethylene glycol) (PEG) molecule. Due to the acid‐labile PBA/catechol complex and the weak‐acid‐stable PBA/sialic acid (SA) complex, the nanoparticles can exhibit a synergetic targeting property for the SA‐overexpressed tumor cells, i.e., the PEG‐caused “passive targeting” and PBA‐triggered “active targeting” under the weakly acidic tumor microenvironment. In addition, the photothermal effect of the polydopamine core and the doxorubicin‐loading capacity of the porous coordination polymer layer endow the nanoparticles with the potential for chemo‐photothermal combination therapy. As expected, the in vitro and in vivo studies both verify that the multifunctional nanoparticles possess relatively lower systematic toxicity, efficient tumor targeting ability, and excellent chemo‐photothermal activity for tumor inhibition. It is believed that these multifunctional nanoparticles with synergetic tumor targeting property and combined therapeutic strategies would provide an insight into the design of a high‐efficiency antitumor nanoplatform for potential clinical applications.     

Leukocyte‐Repelling Biomimetic Immunomagnetic Nanoplatform for High‐Performance Circulating Tumor Cells Isolation

Downstream studies of circulating tumor cells (CTCs), which may provide indicative evaluation information for therapeutic efficacy, cancer metastases, and cancer prognosis, are seriously hindered by the poor purity of enriched CTCs as large amounts of interfering leukocytes still nonspecifically bind to the isolation platform. In this work, biomimetic immunomagnetic nanoparticles (BIMNs) with the following features are designed: i) the leukocyte membrane camouflage, which could greatly reduce homologous leukocyte interaction and actualize high‐purity CTCs isolation, is easily extracted by graphene nanosheets; ii) facile antibody conjugation can be achieved through the “insertion” of biotinylated lipid molecules into leukocyte‐membrane‐coated nanoparticles and streptavidin conjunction; iii) layer‐by‐layer assembly techniques could integrate high‐magnetization Fe₃O₄ nanoparticles and graphene nanosheets efficiently. Consequently, the resulting BIMNs achieve a capture efficiency above 85.0% and CTCs purity higher than 94.4% from 1 mL blood with 20–200 CTCs after 2 min incubation. Besides, 98.0% of the isolated CTCs remain viable and can be directly cultured in vitro. Moreover, application of the BIMNs to cancer patients' peripheral blood shows good reproducibility (mean relative standard deviation 8.7 ± 5.6%). All results above suggest that the novel biomimetic nanoplatform may serve as a promising tool for CTCs enrichment and detection from clinical samples.     

A Multifunctional Biomimetic Nanoplatform for Relieving Hypoxia to Enhance Chemotherapy and Inhibit the PD‐1/PD‐L1 Axis

Hypoxia is reported to participate in tumor progression, promote drug resistance, and immune escape within tumor microenvironment, and thus impair therapeutic effects including the chemotherapy and advanced immunotherapy. Here, a multifunctional biomimetic core–shell nanoplatform is reported for improving synergetic chemotherapy and immunotherapy. Based on the properties including good biodegradability and functionalities, the pH‐sensitive zeolitic imidazolate framework 8 embedded with catalase and doxorubicin constructs the core and serves as an oxygen generator and drug reservoir. Murine melanoma cell membrane coating on the core provides tumor targeting ability and elicits an immune response due to abundance of antigens. It is demonstrated that this biomimetic core–shell nanoplatform with oxygen generation can be partial to accumulate in tumor and downregulate the expression of hypoxia‐inducible factor 1α, which can further enhance the therapeutic effects of chemotherapy and reduce the expression of programmed death ligand 1 (PD‐L1). Combined with immune checkpoints blockade therapy by programmed death 1 (PD‐1) antibody, the dual inhibition of the PD‐1/PD‐L1 axis elicits significant immune response and presents a robust effect in lengthening tumor recurrent time and inhibiting tumor metastasis. Consequently, the multifunctional nanoplatform provides a potential strategy of synergetic chemotherapy and immunotherapy.     

Intra/Extracellular Lactic Acid Exhaustion for Synergistic Metabolic Therapy and Immunotherapy of Tumors

Regulating the tumor microenvironment (TME) has been a promising strategy to improve antitumor therapy. Here, a red blood cell membrane (mRBC)‐camouflaged hollow MnO₂ (HMnO₂) catalytic nanosystem embedded with lactate oxidase (LOX) and a glycolysis inhibitor (denoted as PMLR) is constructed for intra/extracellular lactic acid exhaustion as well as synergistic metabolic therapy and immunotherapy of tumor. Benefiting from the long‐circulation property of the mRBC, the nanosystem can gradually accumulate in a tumor site through the enhanced permeability and retention (EPR) effect. The extracellular nanosystem consumes lactic acid in the TME by catalyzing its oxidation reaction via LOX. Meanwhile, the intracellular nanosystem releases the glycolysis inhibitor to cut off the source of lactic acid, as well as achieve antitumor metabolic therapy through the blockade of the adenosine triphosphate (ATP) supply. Both the extracellular and intracellular processes can be sensitized by O₂, which can be produced during the decomposition of endogenous H₂O₂ catalyzed by the PMLR nanosystem. The results show that the PMLR nanosystem can ceaselessly remove lactic acid, and then lead to an immunocompetent TME. Moreover, this TME regulation strategy can effectively improve the antitumor effect of anti‐PDL1 therapy without the employment of any immune agonists to avoid the autoimmunity.     

A Trojan-Horse-Like Biomimetic Nano-NK to Elicit an Immunostimulatory Tumor Microenvironment for Enhanced GBM Chemo-Immunotherapy

Although the chemo- and immuno-therapies have obtained good responses for several solid tumors, including those with brain metastasis, their clinical efficacy in glioblastoma (GBM) is disappointing. The lack of safe and effective delivery systems across the blood-brain barrier (BBB) and the immunosuppressive tumor microenvironment (TME) are two main hurdles for GBM therapy. Herein, a Trojan-horse-like nanoparticle system is designed, which encapsulates biocompatible PLGA-coated temozolomide (TMZ) and IL-15 nanoparticles (NPs) with cRGD-decorated NK cell membrane (R-NKm@NP), to elicit the immunostimulatory TME for GBM chemo-immunotherapy. Taking advantage of the outer NK cell membrane cooperating with cRGD, the R-NKm@NPs effectively traversed across the BBB and targeted GBM. In addition, the R-NKm@NPs exhibited good antitumor ability and prolonged the median survival of GBM-bearing mice. Notably, after R-NKm@NPs treatment, the locally released TMZ and IL-15 synergistically stimulated the proliferation and activation of NK cells, leading to the maturation of dendritic cells and infiltration of CD8⁺ cytotoxic T cells, eliciting an immunostimulatory TME. Lastly, the R-NKm@NPs not only effectively prolonged the metabolic cycling time of the drugs in vivo, but also has no noticeable side effects. This study may offer valuable insights for developing biomimetic nanoparticles to potentiate GBM chemo- and immuno-therapies in the future.     

Artificial Natural Killer Cells for Specific Tumor Inhibition and Renegade Macrophage Re‐Education

Natural killer (NK) cells can not only recognize and eliminate abnormal cells but also recruit and re‐educate immune cells to protect the host. However, the functions of NK cells are often limited in the immunosuppressive tumor microenvironment (TME). Here, artificial NK cells (designated as aNK) with minor limitations of TME for specific tumor killing and renegade macrophage re‐education are created. The red blood cell membrane (RBCM) cloaks perfluorohexane (PFC) and glucose oxidase (GOX) to construct the aNK. The aNK can directly kill tumor cells by exhausting glucose and generating hydrogen peroxide (H₂O₂). The generated H₂O₂ is also similar to cytokines and chemokines for recruiting immune cells and re‐educating survived macrophages to attack tumor cells. In addition, the oxygen‐carried PFC can strengthen the catalytic reaction of GOX and normalize the hypoxic TME. In vitro and in vivo experiments display that aNK with slight TME limitations exhibit efficient tumor inhibition and immune activation. The aNK will provide a new sight to treat tumor as the supplement of aggressive NK cells.     

Erythrocyte–Platelet Hybrid Membrane Coating for Enhanced Nanoparticle Functionalization

Cell‐membrane‐coated nanoparticles have recently been studied extensively for their biological compatibility, retention of cellular properties, and adaptability to a variety of therapeutic and imaging applications. This class of nanoparticles, which has been fabricated with a variety of cell membrane coatings, including those derived from red blood cells (RBCs), platelets, white blood cells, cancer cells, and bacteria, exhibit properties that are characteristic of the source cell. In this study, a new type of biological coating is created by fusing membrane material from two different cells, providing a facile method for further enhancing nanoparticle functionality. As a proof of concept, the development of dual‐membrane‐coated nanoparticles from the fused RBC membrane and platelet membrane is demonstrated. The resulting particles, termed RBC–platelet hybrid membrane‐coated nanoparticles ([RBC‐P]NPs), are thoroughly characterized, and it is shown that they carry properties of both source cells. Further, the [RBC‐P]NP platform exhibits long circulation and suitability for further in vivo exploration. The reported strategy opens the door for the creation of biocompatible, custom‐tailored biomimetic nanoparticles with varying hybrid functionalities, which may be used to overcome the limitations of current nanoparticle‐based therapeutic and imaging platforms.     

A Dual‐Bioresponsive Drug‐Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade

Patients with advanced melanoma that is of low tumor‐associated antigen (TAA) expression often respond poorly to PD‐1/PD‐L1 blockade therapy. Epigenetic modulators, such as hypomethylation agents (HMAs), can enhance the antitumor immune response by inducing TAA expression. Here, a dual bioresponsive gel depot that can respond to the acidic pH and reactive oxygen species (ROS) within the tumor microenvironment (TME) for codelivery of anti‐PD1 antibody (aPD1) and Zebularine (Zeb), an HMA, is engineered. aPD1 is first loaded into pH‐sensitive calcium carbonate nanoparticles (CaCO₃ NPs), which are then encapsulated in the ROS‐responsive hydrogel together with Zeb (Zeb‐aPD1‐NPs‐Gel). It is demonstrated that this combination therapy increases the immunogenicity of cancer cells, and also plays roles in reversing immunosuppressive TME, which contributes to inhibiting the tumor growth and prolonging the survival time of B16F10‐melanoma‐bearing mice.     

Dual‐Stage Light Amplified Photodynamic Therapy against Hypoxic Tumor Based on an O2 Self‐Sufficient Nanoplatform

Tumor hypoxia severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a liposome‐based nanoparticle (designated as LipoMB/CaO₂) with O₂ self‐sufficient property for dual‐stage light‐driven PDT is demonstrated to address this problem. Through a short time irradiation, ¹O₂ activated by the photosensitizer methylene blue (MB) can induce lipid peroxidation to break the liposome, and enlarge the contact area of CaO₂ with H₂O, resulting in accelerated O₂ production. Accelerated O₂ level further regulates hypoxic tumor microenvironment and in turn improves ¹O₂ generation by MB under another long time irradiation. In vitro and in vivo experiments also demonstrate the superior competence of LipoMB/CaO₂ to alleviate tumor hypoxia, suppress tumor growth and antitumor metastasis with low side‐effect. The O₂ self‐sufficient LipoMB/CaO₂ nanoplatform with dual‐stage light manipulation is a successful attempt for PDT against hypoxic tumor.     

Albumin‐Templated Manganese Dioxide Nanoparticles for Enhanced Radioisotope Therapy

Although nanoparticle‐based drug delivery systems have been widely explored for tumor‐targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia‐associated resistance to radiation‐induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide ¹³¹I labeled human serum albumin (HSA)‐bound manganese dioxide nanoparticles (¹³¹I‐HSA‐MnO₂) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME). Such ¹³¹I‐HSA‐MnO₂ nanoparticles with suitable sizes during blood circulation show rather efficient tumor passive uptake owing to the enhanced permeability and retention effect, as well as little retention in other normal organs to minimize radiotoxicity. The acidic TME can trigger gradual degradation of MnO₂ and thus decomposition of ¹³¹I‐HSA‐MnO₂ nanoparticles into individual ¹³¹I‐HSA with sub‐10 nm sizes and greatly improves intratumoral diffusion. Furthermore, oxygen produced by MnO₂‐triggered decomposition of tumor endogenous H₂O₂ would be helpful to relieve hypoxia‐associated RIT resistant for those tumors. As the results, the ¹³¹I‐HSA‐MnO₂ nanoparticles appear to be a highly effective RIT agent showing great efficacy in tumor treatment upon systemic administration.     

Activating Antitumor Immunity and Antimetastatic Effect Through Polydopamine‐Encapsulated Core–Shell Upconversion Nanoparticles

Synergistic phototherapy has the potential to conquer the extreme heterogeneity and complexity of difficult tumors and result in better cancer treatment outcomes than monomodal photodynamic therapy (PDT) or photothermal therapy (PTT). However, the previous approaches to combining PDT and PTT are mainly focused on primary tumor obliteration while neglecting tumor metastasis, which is responsible for about 90% of cancer deaths. It is shown that a combined PDT/PTT approach, based on upconversion‐polymer hybrid nanoparticles with surface‐loaded chlorin e6 photosensitizer, can enhance primary tumor elimination and elicit antitumor immunity against disseminated tumors. The specifical arrangement of an external upconversion coating over the polymer core ensures adequate photoabsorption by the upconversion nanoparticles for the generation of reactive oxygen species upon single near‐infrared light irradiation. Furthermore, it is found that synergistic phototherapy can elicit robust systemic and humoral antitumor immune responses. When combined with immune checkpoint blockades, it can inhibit tumor relapse and metastasis as well as prolong the survival of tumor‐bearing mice in two types of tumor metastasis models. This study may establish a new modality for enhancing immunogenic cell death through a synergistic phototherapeutic nanoplatform and extend this strategy to overcome tumor metastasis with an augmented antitumor immune response.     

Sequential Targeting TGF‐β Signaling and KRAS Mutation Increases Therapeutic Efficacy in Pancreatic Cancer

Pancreatic cancer is a highly aggressive malignancy that strongly resists extant treatments. The failure of existing therapies is majorly attributed to the tough tumor microenvironment (TME) limiting drug access and the undruggable targets of tumor cells. The formation of suppressive TME is regulated by transforming growth factor beta (TGF‐β) signaling, while the poor response and short survival of almost 90% of pancreatic cancer patients results from the oncogenic KRAS mutation. Hence, simultaneously targeting both the TGF‐β and KRAS pathways might dismantle the obstacles of pancreatic cancer therapy. Here, a novel sequential‐targeting strategy is developed, in which antifibrotic fraxinellone‐loaded CGKRK‐modified nanoparticles (Frax‐NP‐CGKRK) are constructed to regulate TGF‐β signaling and siRNA‐loaded lipid‐coated calcium phosphate (LCP) biomimetic nanoparticles (siKras‐LCP‐ApoE3) are applied to interfere with the oncogenic KRAS. Frax‐NP‐CGKRK successfully targets the tumor sites through the recognition of overexpressed heparan sulfate proteoglycan, reverses the activated cancer‐associated fibroblasts (CAFs), attenuates the dense stroma barrier, and enhances tumor blood perfusion. Afterward, siKras‐LCP‐ApoE3 is efficiently internalized by the tumor cells through macropinocytosis and specifically silencing KRAS mutation. Compared with gemcitabine, this sequential‐targeting strategy significantly elongates the lifespans of pancreatic tumor‐bearing animals, hence providing a promising approach for pancreatic cancer therapy.     

Intelligent Nanocomposites with Intrinsic Blood–Brain‐Barrier Crossing Ability Designed for Highly Specific MR Imaging and Sonodynamic Therapy of Glioblastoma

The blood–brain barrier (BBB) is the most important obstacle to improving the clinical outcomes of diagnosis and therapy of glioblastoma. Thus, the development of a novel nanoplatform that can efficiently traverse the BBB and achieve both precise diagnosis and therapy is of great importance. Herein, an intelligent nanoplatform based on holo‐transferrin (holo‐Tf) with in situ growth of MnO₂ nanocrystals is constructed via a reformative mild biomineralization process. Furthermore, protoporphyrin (ppIX), acting as a sonosensitizer, is then conjugated into holo‐Tf to obtain MnO₂@Tf‐ppIX nanoparticles (TMP). Because of the functional inheritance of holo‐Tf during fabrication, TMP can effectively traverse the BBB for highly specific magnetic resonance (MR) imaging of orthotopic glioblastoma. Clear suppression of tumor growth in a C6 tumor xenograft model is achieved via sonodynamic therapy. Importantly, the experiments also indicate that the TMP nanoplatform has satisfactory biocompatibility and biosafety, which favors potential clinical translation.     

Construction of pH-Sensitive Nanovaccines Encapsulating Tumor Cell Lysates and Immune Adjuvants for Breast Cancer Therapy

The current immunotherapy strategies for triple negative breast cancer (TNBC) are greatly limited due to the immunosuppressive tumor microenvironment (TME). Immunization with cancer vaccines composed of tumor cell lysates (TCL) can induce an effective antitumor immune response. However, this approach also has the disadvantages of inefficient antigen delivery to the tumor tissues and the limited immune response elicited by single-antigen vaccines. To overcome these limitations, a pH-sensitive nanocalcium carbonate (CaCO₃) carrier loaded with TCL and immune adjuvant CpG (CpG oligodeoxynucleotide 1826) is herein constructed for TNBC immunotherapy. This tailor-made nanovaccine, termed CaCO₃@TCL/CpG, not only neutralizes the acidic TME through the consumption of lactate by CaCO₃, which increases the proportion of the M1/M2 macrophages and promotes infiltration of effector immune cells but also activates the dendritic cells in the tumor tissues and recruits cytotoxic T cells to further kill the tumor cells. In vivo fluorescence imaging study shows that the pegylated nanovaccine could stay longer in the blood circulation and extravasate preferentially into tumor site. Besides, the nanovaccine exhibits high cytotoxicity in 4T1 cells and significantly inhibits tumor growth of tumor-bearing mice. Overall, this pH-sensitive nanovaccine is a promising nanoplatform for enhanced immunotherapy of TNBC.     

Antiferromagnetic Pyrite as the Tumor Microenvironment‐Mediated Nanoplatform for Self‐Enhanced Tumor Imaging and Therapy

Several decades of research have identified the specific tumor microenvironment (TME) to develop promising nanotheranostics, such as pH‐sensitive imaging, acidity‐sensitive starving therapy, and hydrogen peroxide‐activated chemotherapy, etc. Herein, a novel TME‐mediated nanoplatform employing antiferromagnetic pyrite nanocubes is presented, exploiting the intratumoral, overproduced peroxide for self‐enhanced magnetic resonance imaging (MRI) and photothermal therapy (PTT)/chemodynamic therapy (CDT). Through the activation of excessive peroxide in the tumor microenvironment, pyrite can lead to in situ surface oxidation and generate hydroxyl radicals to kill tumor cells (i.e., CDT). The increase of the valence state of surface Fe significantly promotes the performance of MRI accompanied by CDT. Furthermore, the localized heat by photothermal treatment can accelerate the intratumoral Fenton process, enabling a synergetic PTT/CDT. To our best knowledge, this is the first study to use the TME‐response valence‐variable strategy based on pyrite for developing a synergetic nanotheranostic, which will open up a new dimension for the design of other TME‐based anticancer strategies.     

A Novel Theranostic Nanoprobe for In Vivo Singlet Oxygen Detection and Real‐Time Dose–Effect Relationship Monitoring in Photodynamic Therapy

Singlet oxygen, as the main member of reactive oxygen species, plays a significant role in cancer photodynamic therapy. However, the in vivo real‐time detection of singlet oxygen remains challenging. In this work, a Förster resonance energy transfer (FRET)‐based upconversion nanoplatform for monitoring the singlet oxygen in living systems is developed, with the ability to evaluate the in vivo dose–effect relationship between singlet oxygen and photodynamic therapy (PDT) efficacy. In details, this nanoplatform is composed of core–shell upconversion nanoparticles (UCNPs), photosensitizer MC540, NIR dye IR‐820, and poly(acryl amine) PAA‐octylamine, where the UCNPs serve as an energy donor while IR‐820 serves as an energy acceptor. The nanoparticles are found to sensitively reflect the singlet oxygen levels generated in the tumor tissues during PDT, by luminescence intensity changes of UNCPs at 800 nm emission. Furthermore, it could also enable tumor treatment with satisfactory biocompatibility. To the best knowledge, this is the first report of a theranostic nanoplatform with the ability to formulate the in vivo dose–effect relationship between singlet oxygen and PDT efficacy and to achieve tumor treatment at the same time. This work might also provide an executable strategy to evaluate photodynamic therapeutic efficacy based on singlet oxygen pathway.     

Engineering Biomimetic Platesomes for pH‐Responsive Drug Delivery and Enhanced Antitumor Activity

Biomimetic camouflage, i.e., using natural cell membranes for drug delivery, has demonstrated advantages over synthetic materials in both pharmacokinetics and biocompatibility, and so represents a promising solution for the development of safe nanomedicine. However, only limited efforts have been dedicated to engineering such camouflage to endow it with optimized or additional properties, in particular properties critical to a “smart” drug delivery system, such as stimuli‐responsive drug release. A pH‐responsive biomimetic “platesome” for specific drug delivery to tumors and tumor‐triggered drug release is described. This platesome nanovehicle is constructed by merging platelet membranes with functionalized synthetic liposomes and exhibits enhanced tumor affinity, due to its platelet membrane–based camouflage, and selectively releases its cargo in response to the acidic microenvironment of lysosomal compartments. In mouse cancer models, it shows significantly better antitumor efficacy than nanoformulations based on a platesome without pH responsiveness or those based on traditional pH‐sensitive liposomes. A convenient way to incorporate stimuli‐responsive features into biomimetic nanoparticles is described, demonstrating the potential of engineered cell membranes as biomimetic camouflages for a new generation of biocompatible and efficient nanocarriers.     

Peptide Nanotube‐Templated Biomineralization of Cu2−xS Nanoparticles for Combination Treatment of Metastatic Tumor

1D peptide nanostructures (i.e., peptide nanotubes, PNTs) exhibit tunable chemo‐physical properties and functions such as improved tissue adhesion, increased cellular uptake, and elongated blood circulation. In this study, the application of PNTs as a desirable 1D template for biomineralization of Cu_2?xS nanoparticles (Cu_2?xS NPs, x = 1–2) is reported. Monodisperse Cu_2?xS NPs are uniformly coated on the peptide nanotubes owing to the specific high binding affinity of Cu ions to the imidazole groups exposed on the surface of nanotubes. The Cu_2?xS NP–coated PNTs are further covalently grafted with an oxaliplatin prodrug (Pt–CuS–PNTs) to construct a versatile nanoplatform for combination cancer therapy. Upon 808 nm laser illumination, the nanoplatform induces significant hyperthermia effect and elicits reactive oxygen species generation through electron transfer and Fenton‐like reaction. It is demonstrated that the versatile nanoplatform dramatically inhibits tumor growth and lung metastasis of melanoma in a B16‐F10 melanoma tumor‐bearing mouse model by combined photo‐ and chemotherapy. This study highlights the ability of PNTs for biomineralization of metal ions and the promising potential of such nanoplatforms for cancer treatment.