Endolysosomal‐Escape Nanovaccines through Adjuvant‐Induced Tumor Antigen Assembly for Enhanced Effector CD8+ T Cell Activation

The activation of tumor‐specific effector immune cells is key for successful immunotherapy and vaccination is a powerful strategy to induce such adaptive immune responses. However, the generation of effective anticancer vaccines is challenging. To overcome these challenges, a novel straight‐forward strategy of adjuvant‐induced tumor antigen assembly to generate nanovaccines with superior antigen/adjuvant loading efficiency is developed. To protect nanovaccines in circulation and to introduce additional functionalities, a biocompatible polyphenol coating is installed. The resulting functionalizable nanovaccines are equipped with a pH (low) insertion peptide (pHLIP) to facilitate endolysosomal escape and to promote cytoplasmic localization, with the aim to enhance cross‐presentation of the antigen by dendritic cells to effectively activate CD8⁺ T cell. The results demonstrate that pHLIP‐functionalized model nanovaccine can induce endolysosomal escape and enhance CD8⁺ T cell activation both in vitro and in vivo. Furthermore, based on the adjuvant‐induced antigen assembly, nanovaccines of the clinically relevant tumor‐associated antigen NY‐ESO‐1 are generated and show excellent capacity to elicit NY‐ESO‐1‐specific CD8⁺ T cell activation, demonstrating a high potential of this functionalizable nanovaccine formulation strategy for clinical applications.     

Nanocage‐Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens Immunity against Cancer

A growing appreciation of the relationship between the immune system and the tumorigenesis has led to the development of strategies aimed at “re‐editing” the immune system to kill tumors. Here, a novel tactic is reported for overcoming the activation‐energy threshold of the immunosuppressive tumor microenvironment and mediating the delivery and presentation of tumor neoantigens to the host's immune system. This nature‐derived nanocage not only efficiently presents ligands that enhance cancer cell phagocytosis, but also delivers drugs that induce immunogenic cancer cell death. The designed nanocage‐therapeutics induce the release of neoantigens and danger signals in dying tumor cells, and leads to enhancement of tumor cell phagocytosis and cross‐priming of tumor specific T cells by neoantigen peptide‐loaded antigen‐presenting cells. Potent inhibition of tumor growth and complete eradication of tumors is observed through systemic tumor‐specific T cell responses in tumor draining lymph nodes and the spleen and further, infiltration of CD8+ T cells into the tumor site. Remarkably, after removal of the primary tumor, all mice treated with this nanocage‐therapeutics are protected against subsequent challenge with the same tumor cells, suggesting development of lasting, tumor‐specific responses. This designed nanocage‐therapeutics “awakens” the host's immune system and provokes a durable systemic immune response against cancer.     

Implantable Synthetic Immune Niche for Spatiotemporal Modulation of Tumor‐Derived Immunosuppression and Systemic Antitumor Immunity: Postoperative Immunotherapy

The development of biomaterial‐based immune niches that can modulate immunosuppressive factors in tumor microenvironment (TME) will be a key technology for improving current cancer immunotherapy. Here, implantable, engineered 3D porous scaffolds are designed to generate synergistic action between myeloid‐derived suppressor cell (MDSC)‐depleting agents, which can accommodate the establishment of a permissive immunogenic microenvironment to counteract tumor‐induced immunosuppression, and cancer vaccines consisting of whole tumor lysates and nanogel‐based adjuvants, which can generate tumor antigen‐specific T cell responses. The local peritumoral implantation of the synthetic immune niche (termed immuneCare‐DISC, iCD) as a postsurgical treatment in an advanced‐stage primary 4T1 breast tumor model generates systemic antitumor immunity and prevents tumor recurrence at the surgical site as well as the migration of residual tumor cells into the lungs, resulting in 100% survival. These therapeutic outcomes are achieved through the inhibition of immunosuppressive MDSCs in tumors and spleens by releasing gemcitabine and recruitment/activation of dendritic cells, enhanced population of CD4⁺ and CD8⁺ T cells, and increased IFN‐γ production by cancer vaccines from the iCD. This combined spatiotemporal modulation of tumor‐derived immunosuppression and vaccine‐induced immune stimulation through the iCD is expected to provide an immune niche for prevention of postoperative tumor recurrence and metastasis.     

PD‐1 Blockade Cellular Vesicles for Cancer Immunotherapy

Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD‐L1 that exhausts antigen‐specific CD8⁺ T cells through PD‐1 receptors. Checkpoint blockade antibodies against PD‐1 or PD‐L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD‐1 receptors on their membranes, which enhance antitumor responses by disrupting the PD‐1/PD‐L1 immune inhibitory axis, are reported. PD‐1 NVs exhibit a long circulation and can bind to the PD‐L1 on melanoma cancer cells. Furthermore, 1‐methyl‐tryptophan, an inhibitor of indoleamine 2,3‐dioxygenase can be loaded into the PD‐1 NVs to synergistically disrupt another immune tolerance pathway in the tumor microenvironment. Additionally, PD‐1 NVs remarkably increase the density of CD8⁺ tumor infiltrating lymphocytes in the tumor margin, which directly drive tumor regression.     

Surface‐Engineering of Red Blood Cells as Artificial Antigen Presenting Cells Promising for Cancer Immunotherapy

The development of artificial antigen presenting cells (aAPCs) to mimic the functions of APCs such as dendritic cells (DCs) to stimulate T cells and induce antitumor immune responses has attracted substantial interests in cancer immunotherapy. In this work, a unique red blood cell (RBC)‐based aAPC system is designed by engineering antigen peptide‐loaded major histocompatibility complex‐I and CD28 activation antibody on RBC surface, which are further tethered with interleukin‐2 (IL2) as a proliferation and differentiation signal. Such RBC‐based aAPC‐IL2 (R‐aAPC‐IL2) can not only provide a flexible cell surface with appropriate biophysical parameters, but also mimic the cytokine paracrine delivery. Similar to the functions of matured DCs, the R‐aAPC‐IL2 cells can facilitate the proliferation of antigen‐specific CD8+ T cells and increase the secretion of inflammatory cytokines. As a proof‐of‐concept, we treated splenocytes from C57 mice with R‐aAPC‐IL2 and discovered those splenocytes induced significant cancer‐cell‐specific lysis, implying that the R‐aAPC‐IL2 were able to re‐educate T cells and induce adoptive immune response. This work thus presents a novel RBC‐based aAPC system which can mimic the functions of antigen presenting DCs to activate T cells, promising for applications in adoptive T cell transfer or even in direct activation of circulating T cells for cancer immunotherapy.     

Bio‐Orthogonal T Cell Targeting Strategy for Robustly Enhancing Cytotoxicity against Tumor Cells

T cells can kill tumor cells by cell surface immunological recognition, but low affinity for tumor‐associated antigens could lead to T cell off‐target effects. Herein, a universal T cell targeting strategy based on bio‐orthogonal chemistry and glycol‐metabolic engineering is introduced to enhance recognition and cytotoxicity of T cells in tumor immunotherapy. Three kinds of bicycle [6.1.0] nonyne (BCN)‐modified sugars are designed and synthesized, in which Ac₄ManN‐BCN shows efficient incorporation into wide tumor cells with a BCN motif on surface glycans. Meanwhile, activated T cells are treated with Ac₄GalNAz to introduce azide (N₃) on the cell surface, initiating specific tumor targeting through a bio‐orthogonal click reaction between N₃ and BCN. This artificial targeting strategy remarkably enhances recognition and migration of T cells to tumor cells, and increases the cytotoxicity 2 to 4 times for T cells against different kinds of tumor cells. Surprisingly, based on this strategy, the T cells even exhibit similar cytotoxicity with the chimeric antigen receptor T‐cell against Raji cells in vitro at the effector: target cell ratios (E:T) of 1:1. Such a universal bio‐orthogonal T cell‐targeting strategy might further broaden applications of T cell therapy against tumors and provide a new strategy for T cell modification.     

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.     

Development of an In Situ Cancer Vaccine via Combinational Radiation and Bacterial‐Membrane‐Coated Nanoparticles

Neoantigens induced by random mutations and specific to an individual's cancer are the most important tumor antigens recognized by T cells. Among immunologically “cold” tumors, limited recognition of tumor neoantigens results in the absence of a de novo antitumor immune response. These “cold” tumors present a clinical challenge as they are poorly responsive to most immunotherapies, including immune checkpoint inhibitors (ICIs). Radiation therapy (RT) can enhance immune recognition of “cold” tumors, resulting in a more diversified antitumor T‐cell response, yet RT alone rarely results in a systemic antitumor immune response. Therefore, a multifunctional bacterial membrane‐coated nanoparticle (BNP) composed of an immune activating PC7A/CpG polyplex core coated with bacterial membrane and imide groups to enhance antigen retrieval is developed. This BNP can capture cancer neoantigens following RT, enhance their uptake in dendritic cells (DCs), and facilitate their cross presentation to stimulate an antitumor T‐cell response. In mice bearing syngeneic melanoma or neuroblastoma, treatment with BNP+RT results in activation of DCs and effector T cells, marked tumor regression, and tumor‐specific antitumor immune memory. This BNP facilitates in situ immune recognition of a radiated tumor, enabling a novel personalized approach to cancer immunotherapy using off‐the‐shelf therapeutics.     

Red Blood Cell Membrane as a Biomimetic Nanocoating for Prolonged Circulation Time and Reduced Accelerated Blood Clearance

For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have reported a phenomenon known as “accelerated blood clearance (ABC)” where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane‐coated Fe₃O₄ nanoparticles (Fe₃O₄@RBC NPs) rely on CD47, which is a “don't eat me” marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein‐alpha (SIRP‐α) receptor. Fe₃O₄@RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe₃O₄@RBC NPs does not elicit immune responses on neither the cellular level (myeloid‐derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane‐camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long‐existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance.     

Distinct Immune Signatures in Peripheral Blood Predict Chemosensitivity in Intrahepatic Cholangiocarcinoma Patients

Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. Chemotherapy remains the main therapeutic strategy for advanced ICC patients, but chemosensitivity varies individually. Here, we applied cytometry by time-of-flight (CyTOF) to establish the immune profile of peripheral blood mononuclear cells (PBMCs) on the single-cell level at indicated time points before, during, and after chemotherapy. Multiplex immunofluorescence staining was applied to examine the spatial distribution of certain immune clusters. Tissue microarrays (TMAs) were used for prognostic evaluation. A total of 20 ICC patients treated with gemcitabine (GEM) were enrolled in our study, including eight cases with good response (R) and 12 cases with non-response (NR). Tremendous changes in PBMC composition, including an increased level of CD4/CD8 double-positive T cells (DPT), were observed after chemotherapy. Patients with higher level of CD4⁺CD45RO⁺CXCR3⁺ T cells before treatment had a favorable response to chemotherapy. Our study identified a positive correlation between the percentage of T cell subpopulations and clinical response after chemotherapy, which suggests that it is practical to predict the potential response before treatment by evaluating the proportions of the cell population in PBMCs.     

Hollow ZnO Nanospheres Enhance Anticancer Immunity by Promoting CD4+ and CD8+ T Cell Populations In Vivo

Appropriate adjuvant aiding in generating robust anticancer immunity is crucial for cancer immunotherapy. Herein, hollow ZnO (HZnO) nanospheres are synthesized by a facile method using carbon nanospheres as the template. The HZnO nanospheres significantly promote the cellular uptake of a model antigen, and cytokine secretion by antigen‐presenting cells in vitro. HZnO loaded with ovalbumin and polyinosinic‐polycytidylic acid (poly(I:C)) inhibits cancer growth and metastasis to inguinal lymph node in a cancer cell challenge model. Moreover, HZnO loaded with autologous cancer antigens inhibits cancer cell growth in a cancer cell re‐challenge model. HZnO nanospheres significantly improve the CD4⁺ and/or CD8⁺ T cell population in splenocytes of mice in both cancer cell challenge model and re‐challenge model. The HZnO nanospheres can be used for cancer immunotherapy as adjuvant.     

Platelet Membrane‐Camouflaged Magnetic Nanoparticles for Ferroptosis‐Enhanced Cancer Immunotherapy

Although cancer immunotherapy has emerged as a tremendously promising cancer therapy method, it remains effective only for several cancers. Photoimmunotherapy (e.g., photodynamic/photothermal therapy) could synergistically enhance the immune response of immunotherapy. However, excessively generated immunogenicity will cause serious inflammatory response syndrome. Herein, biomimetic magnetic nanoparticles, Fe₃O₄‐SAS @ PLT, are reported as a novel approach to sensitize effective ferroptosis and generate mild immunogenicity, enhancing the response rate of non‐inflamed tumors for cancer immunotherapy. Fe₃O₄‐SAS@PLT are built from sulfasalazine (SAS)‐loaded mesoporous magnetic nanoparticles (Fe₃O₄) and platelet (PLT) membrane camouflage and triggered a ferroptotic cell death via inhibiting the glutamate‐cystine antiporter system X_c^? pathway. Fe₃O₄‐SAS @ PLT‐mediated ferroptosis significantly improves the efficacy of programmed cell death 1 immune checkpoint blockade therapy and achieves a continuous tumor elimination in a mouse model of 4T1 metastatic tumors. Proteomics studies reveal that Fe₃O₄‐SAS @ PLT‐mediated ferroptosis could not only induce tumor‐specific immune response but also efficiently repolarize macrophages from immunosuppressive M2 phenotype to antitumor M1 phenotype. Therefore, the concomitant of Fe₃O₄‐SAS @ PLT‐mediated ferroptosis with immunotherapy are expected to provide great potential in the clinical treatment of tumor metastasis.     

Tumor Microenvironment‐Activatable Prodrug Vesicles for Nanoenabled Cancer Chemoimmunotherapy Combining Immunogenic Cell Death Induction and CD47 Blockade

Chemoimmunotherapy is reported to activate a robust T cell antitumor immune response by triggering immunogenic cell death (ICD), which has initiated a number of clinical trials. However, current chemoimmunotherapy is restricted to a small fraction of patients due to low drug delivery efficacy and immunosuppression within the tumor microenvironment. A tumor microenvironment‐activatable prodrug vesicle for cancer chemoimmunotherapy using ICD is herein reported. The prodrug vesicles are engineered by integrating an oxaliplatin (OXA) prodrug and PEGylated photosensitizer (PS) into a single nanoplatform, which show tumor‐specific accumulation, activation, and deep penetration in response to the tumoral acidic and enzymatic microenvironment. It is demonstrated that codelivery of OXA prodrug and PS can trigger ICD of the tumor cells by immunogenic cells killing. The combination of prodrug vesicle‐induced ICD with Î ± CD47‐mediated CD47 blockade further facilitates dendritic cell (DC) maturation, promotes antigen presentation by DCs, and eventually propagates the antitumor immunity of ICD. CD47 blockade and ICD induction efficiently inhibit the growth of both primary and abscopal tumors, suppress tumor metastasis, and prevent tumor recurrence. Collectively, these results imply that boosting antitumor immunity using ICD induction and suppressing tumor immune evasion via CD47 blockade might be promising for improved cancer chemoimmunotherapy.     

Cytokine Secreting Microparticles Engineer the Fate and the Effector Functions of T‐Cells

T‐cell immunotherapy is a promising approach for cancer, infection, and autoimmune diseases. However, significant challenges hamper its therapeutic potential, including insufficient activation, delivery, and clonal expansion of T‐cells into the tumor environment. To facilitate T‐cell activation and differentiation in vitro, core–shell microparticles are developed for sustained delivery of cytokines. These particles are enriched by heparin to enable a steady release of interleukin‐2 (IL‐2), the major T‐cell growth factor, over 10+ d. The controlled delivery of cytokines is used to steer lineage specification of cultured T‐cells. This approach enables differentiation of T‐cells into central memory and effector memory subsets. It is shown that the sustained release of stromal cell‐derived factor 1α could accelerate T‐cell migration. It is demonstrated that CD4+ T‐cells could be induced to high concentrations of regulatory T‐cells through controlled release of IL‐2 and transforming growth factor beta. It is found that CD8+ T‐cells that received IL‐2 from microparticles are more likely to gain effector functions as compared with traditional administration of IL‐2. Culture of T‐cells within 3D scaffolds that contain IL‐2‐secreting microparticles enhances proliferation as compared with traditional, 2D approaches. This yield a new method to control the fate of T‐cells and ultimately to new strategies for immune therapy.     

The Binding of rhBMP‐2 to the Receptors of viable MC3T3‐E1 Cells and the Question of Cooperativity

The binding of rhBMP‐2 to its receptors, the signal transduction cascade and the final responses of bone cells, osteoprogenitor cells and derived cell lines is of high fundamental and clinical interest. In this report concentration‐response curves of the osteoblast cell line MC3T3‐E1 under influence of rhBMP‐2 was investigated. The biological response of the cells (corresponding to a down‐stream effect of the receptor state‐function) was monitored in pilot experiments by the MC3T3‐cell alkaline phosphatase‐induction test (MC3T3‐cell ALP‐induction test). It is shown that the MC3T3‐cell ALP‐induction test is a good tool for measuring biologically active recombinant human BMP‐2 (rhBMP‐2) in crude extracts of E. coli as well as in highly purified form. In addition this test is very sensitive to chemically induced structural changes of rhBMP‐2 such as those resulting from a radiolabeling of rhBMP‐2 by the Bolton‐Hunter procedure. The latter procedure reduces the biological activity of rhBMP‐2 by a factor of 3–4. The measured concentration‐response curves could all be non‐linearly fitted to a rectangular hyperbola. The half‐maximal saturation, K_0.5, is found between 30–100 nM rhBMP‐2 (= 0.8–2.5 μg/ml). The effect of rhBMP‐2 shows a plateau i.e. maximal response at ca. 300–1000 nM rhBMP‐2 (= 8–25 μg/ml). The data thus indicate a non‐cooperative binding‐response behavior. This was unexpected since BMP‐2 binds simultaneously to two cooperating receptors of type 1 and type 2. However in the very low concentration range of employed rhBMP‐2 a variable response of the cells was measured so that a full exclusion of cooperativity cannot be concluded at the present time. This will be clarified by future experiments.     

Microneedle‐Assisted,DC‐Targeted Codelivery of pTRP‐2 and Adjuvant of Paclitaxel for Transcutaneous Immunotherapy

This work aims at developing an immunotherapeutic strategy to deliver a cancer DNA vaccine targeting dendritic cells (DCs), to trigger their maturation and antitumor function, and reduce immune escape using a polymeric nanocomplex of paclitaxel (PTX)‐encapsulated sulfobutylether‐β‐cyclodextrin (SBE)/mannosylated N,N,N‐trimethylchitosan (mTMC)/DNA. To enhance DC‐targeting and revoke immunosuppression is the major challenge for eliciting effective antitumor immunity. This codelivery system is characterized by using low‐dose PTX as an adjuvant that is included inside SBE, and the PTX/SBE further serves as an anionic crosslinker to self‐assemble with the cationic mTMC/DNA polyplexes. This system is used in combination with a microneedle for transcutaneous vaccination. Once penetrating into the epidermis, the mannosylated nanocomplexes would preferentially deliver the pTRP‐2 DNA vaccine inside the DCs. Phenotypic maturation is demonstrated by the increased expression of costimulatory molecules of CD80 and CD86, and the elevated secretion of IL‐12p70. The mixed leucocyte reactions reveal that the PTX/SBE‐mTMC/DNA nanocomplexes enhance the proliferation of CD4+ and CD8+ T cells, and inhibit the generation of immune‐suppressive FoxP3+ T cells. The system shows high antitumor efficacy in vivo. The PTX/SBE‐mTMC/DNA nanocomplexes for DC‐targeted codelivery of DNA vaccine and adjuvant PTX yield synergistic effects on the DC maturation and its presenting functions, thus increasing immune stimulation and reducing immune escape.     

A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes

Emerging evidence indicates that exosomes derived from gastric cancer cells enhance tumor migration and invasion through the modulation of the tumor microenvironment. However, it remains a major problem to detect cancer‐specific exosomes due to technical and biological challenges. Most of the methods reported could not achieve efficient detection of tumor‐derived exosomes in the background of normal exosomes. Herein, a label‐free electrochemical aptasensor is presented for specific detection of gastric cancer exosomes. This platform contains an anti‐CD63 antibody modified gold electrode and a gastric cancer exosome specific aptamer. The aptamer is linked to a primer sequence that is complementary to a G‐quadruplex circular template. The presence of target exosomes could trigger rolling circle amplification and produce multiple G‐quadruplex units. This horseradish peroxidase mimicking DNAzyme could catalyze the reduction of H₂O₂ and generate electrochemical signals. This aptasensor exhibits high selectivity and sensitivity toward gastric cancer exosomes with a detection limit of 9.54 × 10² mL^?1 and a linear response range from 4.8 × 10³ to 4.8 × 10⁶ exosomes per milliliter. Therefore, this electrochemical aptasensor is expected to become a useful tool for the early diagnosis of gastric cancer.     

Personalized Cancer Immunotherapy via Transporting Endogenous Tumor Antigens to Lymph Nodes Mediated by Nano Fe3O4

While immunotherapy has a tremendous clinical potential to combat cancer, immune responses generated by conventional cancer immunotherapy remain not enough to completely eliminate tumors, mainly due to the tumor's immunosuppressive microenvironment and heterogeneity of tumor immunogenicity. To improve antitumor immune responses and realize personalized immunotherapy, in this report, endogenous tumor antigens (ETAs) that dynamically present on tumor cells are transported to lymph nodes (LNs). Based on the hypothesis that nano Fe₃O₄ (≈10 nm) could serve as the nanocarrier for transporting ETAs from the tumor to LNs, we wondrously find that Fe₃O₄ has a tremendous potential to improve cancer immunotherapy, because of its excellent protein‐captured efficiency and LNs‐targeted ability. To ensure the optimal ETAs‐bound efficiency of Fe₃O₄, a core–shell formulation (denoted as Ce6/Fe₃O₄‐L) is developed and specific release of Fe₃O₄ in tumor is enabled. These findings provide a simple and general strategy for boosting cytotoxic T‐cell response and realizing personalized cancer immunotherapy simultaneously.     

Surface Passivation for Reliable Measurement of Bulk Electronic Properties of Heterojunction Devices

Quantum efficiency measurements of state of the art Cu(In,Ga)Se₂ (CIGS) thin film solar cells reveal current losses in the near infrared spectral region. These losses can be ascribed to inadequate optical absorption or poor collection of photogenerated charge carriers. Insight on the limiting mechanism is crucial for the development of more efficient devices. The electron beam induced current measurement technique applied on device cross‐sections promises an experimental access to depth resolved information about the charge carrier collection probability. Here, this technique is used to show that charge carrier collection in CIGS deposited by multistage co‐evaporation at low temperature is efficient over the optically active region and collection losses are minor as compared to the optical ones. Implications on the favorable absorber design are discussed. Furthermore, it is observed that the measurement is strongly affected by cross‐section surface recombination and an accurate determination of the collection efficiency is not possible. Therefore it is proposed and shown that the use of an Al₂O₃ layer deposited onto the cleaved cross‐section significantly improves the accuracy of the measurement by reducing the surface recombination. A model for the passivation mechanism is presented and the passivation concept is extended to other solar cell technologies such as CdTe and Cu₂(Zn,Sn)(S,Se)₄.     

Encapsulation of Hydrophilic and Hydrophobic Peptides into Hollow Mesoporous Silica Nanoparticles for Enhancement of Antitumor Immune Response

Codelivery of combinational antigenic peptides and adjuvant to antigen presenting cells is expected to amplify tumor specific T lymphocytes immune responses while minimizing the possibility of tumor escaping and reducing immune tolerance to single antigenic peptide. However, the varied hydrophobicities of these multivariant derived short antigenic peptides limit their codelivery efficiency in conventional delivery systems. Here, a facile yet effective route is presented to generate monodisperse and stable hollow mesoporous silica nanoparticles (HMSNs) for codelivering of HGP100_25–33 and TRP2_180–188, two melanoma‐derived peptides with varied hydrophobicities. The HMSNs with large pore size can improve the encapsulation efficiency of both HGP100 and TRP2 after ? NH₂ modification on the inner hollow core and ? COOH modification in the porous channels. HGP100 and TRP2 loaded HMSNs (HT@HMSNs) are further enveloped within monophosphoryl lipid A adjuvant entrapped lipid bilayer (HTM@HMLBs), for improved stability/biocompatibility and codelivery efficiency of multiple peptides, adjuvant, and enhanced antitumor immune responses. HTM@HMLBs increase uptake by dendritic cells (DCs) and stimulate DCs maturation efficiently, which further induce the activation of both tumor specific CD8⁺ and CD4⁺ T lymphocytes. Moreover, HTM@HMLBs can significantly inhibit tumor growth and lung metastasis in murine melanoma models with good safety profiles. HMSNs enveloped with lipid bilayers (HMLBs) are believed to be a promising platform for codelivery of multiple peptides, adjuvant, and enhancement of antitumor efficacy of conventional vaccinations.