Engineering nanoparticles-enabled tumor-associated macrophages repolarization and phagocytosis restoration for enhanced cancer immunotherapy.

Tumor-associated macrophages (TAMs) are pivotal within the immunosuppressive tumor microenvironment (TME), and recently, have attracted intensive attention for cancer treatment. However, concurrently to promote TAMs repolarization and phagocytosis of cancer cells remains challenging. Here, a TAMs-targeted albumin nanoparticles-based delivery system (M@SINPs) was constructed for the co-delivery of photosensitizer IR820 and SHP2 inhibitor SHP099 to potentiate macrophage-mediated cancer immunotherapy. M@SINPs under laser irradiation can generate the intracellular reactive oxygen species (ROS) and facilitate M2-TAMs to an M1 phenotype. Meanwhile, inhibition of SHP2 could block the CD47-SIRPa pathway to restore M1 macrophage phagocytic activity. M@SINPs-mediated TAMs remodeling resulted in the immunostimulatory TME by repolarizing TAMs to an M1 phenotype, restoring its phagocytic function and facilitating intratumoral CTLs infiltration, which significantly inhibited tumor growth. Furthermore, M@SINPs in combination with anti-PD-1 antibody could also improve the treatment outcomes of PD-1 blockade and exert the synergistic anticancer effects. Thus, the macrophage repolarization/phagocytosis restoration combination through M@SINPs holds promise as a strategy to concurrently remodel TAMs in TME for improving the antitumor efficiency of immune checkpoint block and conventional therapy.

Electromagnetic Interference Effects of Continuous Waves on Memristors: A Simulation Study.

As two-terminal passive fundamental circuit elements with memory characteristics, memristors are promising devices for applications such as neuromorphic systems, in-memory computing, and tunable RF/microwave circuits. The increasingly complex electromagnetic interference (EMI) environment threatens the reliability of memristor systems. However, various EMI signals' effects on memristors are still unclear. This paper selects continuous waves (CWs) as EMI signals. It provides a deeper insight into the interference effect of CWs on the memristor driven by a sinusoidal excitation voltage, as well as a method for investigating the EMI effect of memristors. The optimal memristor model is obtained by the exhaustive traversing of the possible model parameters, and the interference effect of CWs on memristors is quantified based on this model and the proposed evaluation metrics. Simulation results indicate that CW interference may affect the switching time, dynamic range, nonlinearity, symmetry, time to the boundary, and variation of memristance. The specific interference effect depends on the operating mode of the memristor, the amplitude, and the frequency of the CW. This research provides a foundation for evaluating EMI effects and designing electromagnetic protection for memristive neuromorphic systems.

Indoor Localization Method of Personnel Movement Based on Non-Contact Electrostatic Potential Measurements.

The indoor localization of people is the key to realizing "smart city" applications, such as smart homes, elderly care, and an energy-saving grid. The localization method based on electrostatic information is a passive label-free localization technique with a better balance of localization accuracy, system power consumption, privacy protection, and environmental friendliness. However, the physical information of each actual application scenario is different, resulting in the transfer function from the human electrostatic potential to the sensor signal not being unique, thus limiting the generality of this method. Therefore, this study proposed an indoor localization method based on on-site measured electrostatic signals and symbolic regression machine learning algorithms. A remote, non-contact human electrostatic potential sensor was designed and implemented, and a prototype test system was built. Indoor localization of moving people was achieved in a 5 m × 5 m space with an 80% positioning accuracy and a median error absolute value range of 0.4-0.6 m. This method achieved on-site calibration without requiring physical information about the actual scene. It has the advantages of low computational complexity and only a small amount of training data is required.

Quantification of degeneracy in Hodgkin-Huxley neurons on Newman-Watts small world network.

Degeneracy is a fundamental source of biological robustness, complexity and evolvability in many biological systems. However, degeneracy is often confused with redundancy. Furthermore, the quantification of degeneracy has not been addressed for realistic neuronal networks. The objective of this paper is to characterize degeneracy in neuronal network models via quantitative mathematic measures. Firstly, we establish Hodgkin-Huxley neuronal networks with Newman-Watts small world network architectures. Secondly, in order to calculate the degeneracy, redundancy and complexity in the ensuing networks, we use information entropy to quantify the information a neuronal response carries about the stimulus - and mutual information to measure the contribution of each subset of the neuronal network. Finally, we analyze the interdependency of degeneracy, redundancy and complexity - and how these three measures depend upon network architectures. Our results suggest that degeneracy can be applied to any neuronal network as a formal measure, and degeneracy is distinct from redundancy. Qualitatively degeneracy and complexity are more highly correlated over different network architectures, in comparison to redundancy. Quantitatively, the relationship between both degeneracy and redundancy depends on network coupling strength: both degeneracy and redundancy increase with complexity for small coupling strengths; however, as coupling strength increases, redundancy decreases with complexity (in contrast to degeneracy, which is relatively invariant). These results suggest that the degeneracy is a general topologic characteristic of neuronal networks, which could be applied quantitatively in neuroscience and connectomics.

Doxorubicin-loaded micelles based on multiarm star-shaped PLGA-PEG block copolymers: influence of arm numbers on drug delivery.

Star-shaped block copolymers based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) (st-PLGA-PEG) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of st-PLGA-PEG copolymers and their micelle properties. st-PLGA-PEG copolymers with arm numbers 3, 4 and 6 were synthesized by using different cores such as trimethylolpropane, pentaerythritol and dipentaerythritol, and were characterized by nuclear magnetic resonance and gel permeation chromatography. The critical micelle concentration decreased with increasing arm numbers in st-PLGA-PEG copolymers. The doxorubicin-loaded st-PLGA-PEG micelles were prepared by a modified nanoprecipitation method. Micellar properties such as particle size, drug loading content and in vitro drug release behavior were investigated as a function of the number of arms and compared with each other. The doxorubicin-loaded 4-arm PLGA-PEG micelles were found to have the highest cellular uptake efficiency and cytotoxicity compared with 3-arm PLGA-PEG micelles and 6-arm PLGA-PEG micelles. The results suggest that structural tailoring of arm numbers from st-PLGA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency. Structural tailoring of arm numbers from star shaped-PLGA-PEG copolymers (3-arm/4-arm/6-arm-PLGA-PEG) could provide a new strategy for designing drug carriers of high efficiency.

Paclitaxel-loaded polymeric micelles based on poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) triblock copolymers: in vitro and in vivo evaluation.

The purpose of this study was to develop polymeric nanoscale drug-delivery system (nano-DDS) for paclitaxel (PTX) from poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) (PCL-PEG-PCL, PCEC) copolymers, intended to be intravenously administered, able to improve the therapeutic efficacy of the drug and devoid of the adverse effects of Cremophor EL. Both of the PTX-loaded polymeric micelles and polymersomes were successfully prepared from PCEC copolymers. The obtained PTX-loaded micelles exhibited core-shell morphology with satisfactory size (93 nm), and were favorable for intravenous injection. In vitro cytotoxicity demonstrated that the cytotoxic effect of PTX-loaded micelles was lower than that of Taxol (Bristol-Myers Squibb, Princeton, New Jersey). Pharmacokinetic results indicated that the PTX-loaded micelles had longer systemic circulation time and slower plasma elimination rate than those of Taxol. Furthermore, PTX-loaded micelles showed greater tumor growth-inhibition effect in vivo on EMT6 breast tumor, in comparison with Taxol. Therefore, the prepared polymeric micelles might be potential nano-DDS for PTX delivery in cancer chemotherapy.

Dynamic Gesture Recognition Model Based on Millimeter-Wave Radar With ResNet-18 and LSTM.

In this article, a multi-layer convolutional neural network (ResNet-18) and Long Short-Term Memory Networks (LSTM) model is proposed for dynamic gesture recognition. The Soli dataset is based on the dynamic gesture signals collected by millimeter-wave radar. As a gesture sensor radar, Soli radar has high positional accuracy and can recognize small movements, to achieve the ultimate goal of Human-Computer Interaction (HCI). A set of velocity-range Doppler images transformed from the original signal is used as the input of the model. Especially, ResNet-18 is used to extract deeper spatial features and solve the problem of gradient extinction or gradient explosion. LSTM is used to extract temporal features and solve the problem of long-time dependence. The model was implemented on the Soli dataset for the dynamic gesture recognition experiment, where the accuracy of gesture recognition obtained 92.55%. Finally, compare the model with the traditional methods. The result shows that the model proposed in this paper achieves higher accuracy in dynamic gesture recognition. The validity of the model is verified by experiments.

Design of Light-Activated Nanoplatform through Boosting "Eat Me" Signals for Improved CD47-Blocking Immunotherapy.

Here, the authors propose a light-activated reactive oxygen species (ROS)-responsive nanoplatform that can boost immunogenic cell death (ICD) to release "eat me" signals, and improve CD47-blocking immunotherapy by tumor-targeted codelivery of photosensitizer IR820 and anti-CD47 antibody (αCD47). Human serum albumin and αCD47 are first constructed into a single nanoparticle using ROS-responsive linkers, which are further conjugated with photosensitizer IR820 via a matrix metalloproteinase-sensitive peptide as linker and then modified with poly(ethylene glycol) on the surface of the obtained nanoparticles. When exposed to the first wave of near-infrared (NIR) laser irradiation, the obtained nanoplatform (M-IR820/αCD47@NP) can generate ROS, which triggers nanoparticles dissociation and thus, facilitates the release of αCD47 and IR820. The second wave of NIR laser irradiation is subsequently used to perform phototherapy and induce ICD of tumor cells. An in vitro cellular study shows that M-IR820/αCD47@NP can stimulate dendritic cells activation while simultaneously enhancing the phagocytic activity of macrophage against tumor cells. In 4T1 tumor-bearing mice, M-IR820/αCD47@NP-mediated combination of phototherapy and CD47 blockade can effectively induce the synergistic antitumor immune responses to inhibit the growth of tumors and prevent local tumor recurrence. This work offers a promising strategy to improve the CD47-blocking immunotherapy efficacy using αCD47 nanomedicine.

Tumor microenvironment-activated therapeutic peptide-conjugated prodrug nanoparticles for enhanced tumor penetration and local T cell activation in the tumor microenvironment.

Nanomedicine-based chemoimmunotherapy has shown a great potential for cancer therapies application in recent years. However, most nanoparticles still face a problem of low accumulation and limited penetration of chemotherapeutic drugs and immunotherapeutic drugs into solid tumors. Here, we developed a tumor microenvironment (TME)-activable therapeutic peptide-conjugated prodrug nanoparticle for enhanced tumor penetration and synergistic antitumor effects of chemotherapy and immune checkpoint blockade therapy. The prodrug nanoparticle is composed of a short D-peptide antagonist of PD-L1 (DPPA) conjugated doxorubicin (DOX) prodrug and a PEGylated DOX prodrug, which can dissociate into small DOX nanoparticles (<30 nm) and release DPPA antagonist in TME. The prodrug nanoparticles could co-deliver DOX and DPPA antagonist by one nanocarrier and improve tumor accumulation and penetration of the prodrug nanoparticels via a transcytosis process. It is demonstrated that co-delivery of DOX and DPPA antagonist directly killed tumor cells, promoted the tumor-infiltrating cytotoxic T lymphocytes, reduced the tumor-infiltrating regulatory T cells, and elicited a long-term immune memory effect to prevent tumor recurrence and metastasis. This TME-activable prodrug nanoparticle holds promise as a co-delivery nanoplatform for the improved chemoimmunotherapy of solid tumors.

Effective antitumor activity of paclitaxel-loaded poly (epsilon-caprolactone)/pluronic F68 nanoparticles after intratumoral delivery into the murine breast cancer model.

A paclitaxel-loaded poly (epsilon]-caprolactone)(PCL)/pluronic F68 (F68) nanoparticle formulation was prepared as an intratumoral delivery system to assess its potential for future neoadjuvant chemotherapy application in the treatment of breast cancer. Paclitaxel-loaded nanoparticles were prepared by a solvent evaporation method using the self-synthesized PCL/F68 compound. Prepared nanoparticles were spherical with a rough, porous surface. As described in our earlier study, F68 was incorporated into the PCL matrix as both a pore-forming agent and to enhance drug release from the particles. A murine breast cancer model has shown that when using equivalent paclitaxel doses, paclitaxel-loaded PCL/F68 nanoparticles administered by a single intratumoral injection were more efficient in impeding tumor development than conventional paclitaxel injections administered by multiple intraperitoneal injections. In conclusion, paclitaxel-loaded PCL/F68 nanoparticles can be delivered intratumorally and they effectively prevent tumor cell growth and establishment in a localized area. This treatment shows promise as a future neoadjuvant chemotherapy application in the treatment of breast cancer.

Research on action behavior of neuron system in case of single pulse stimulus.

Facing on the complex electromagnetic environment of electrical equipment, based on the bio-anti-interference characteristics of neuron system, the bio-inspired electromagnetic protection is proposed in order to improve and assist the traditional electromagnetic protection method. In order to analyze the dynamical characteristics of electrical signal transfer process of neuron system, Hodgkin-Huxley (HH) model is adopted to calculate the action potential of single neuron. The initial value problem used in the parameters of Hodgkin-Huxley model is studied in order to satisfy the physiological phenomenon. The stability of HH model is analyzed to assess the dynamic stable performance of neuron. Based on the investigation of single neuron, a simple neuron system consisted of two neurons and one synapse is studied. The compassion between the action potential of posterior neuron and different synapse is performed, which explores how the mathematic models of different synapses influence the action potential. The relationship between action potential of posterior neuron and coupling strength of simplified synapse is calculated to explain the diversity of electrical signal output of neuron system. These numerical results enable to provide some datum for deeply developing the bio-inspired electromagnetic protection and well designing the bio-inspired circuit.

Tumor microenvironment-responsive prodrug nanoplatform via co-self-assembly of photothermal agent and IDO inhibitor for enhanced tumor penetration and cancer immunotherapy.

Nanomedicine-based phototherapy in combination with immune checkpoint blockade therapy has been reported as a promising strategy for improved cancer immunotherapy. However, tumor penetration of nanomedicine into solid tumor is still an unresolved obstacle to an effective drug delivery, leading to limitations in their applications. Here, we developed a tumor microenvironment-responsive prodrug nanoplatform for efficient penetration and photo-immunotherapy of cancer. The prodrug nanoplatform is performed by integrating PEGylated indoleamine-2,3-dioxygenase (IDO) inhibitor (Epacadostat) and photosensitizer (Indocyanine green, ICG) into a core-shell nanostructure via intermolecular interactions, which can transform into small dual-drug complexes (<40 nm) at tumor microenvironment. The resulting small dual-drug complexes could undergo caveolae-mediated endocytosis, enhance cellular uptake, directly kill tumor cells, in situ trigger antitumor immune response and modulate IDO-mediated immunosuppression. More significantly, the prodrug nanoplatform in combination with PD-L1 checkpoint blockade synergistically promoted the antitumor immunity and efficiently inhibited the growth of both primary and abscopal tumors. The present study provides a novel delivery strategy for nanoenabled phototherapy and IDO inhibition to combine PD-L1 checkpoint blockade for achieving more effective therapy of solid tumors.

Antigen-Inorganic Hybrid Flowers-Based Vaccines with Enhanced Room Temperature Stability and Effective Anticancer Immunity.

Particle-based antigen carriers as adjuvants play an important role in vaccine development. Herein, an antigen-inorganic hybrid flower-like particle is developed as a novel vaccine carrier. Model antigen ovalbumin (OVA)-copper (II) sulfate hybrid vaccines (OVA-Cu-HVs) are mildly and facilely constructed through a biomimetic mineralization process. OVA-Cu-HVs facilitate cellular uptake in antigen-presenting cells and the internalization of OVA-Cu-HVs involves macropinocytosis-mediated endocytosis. OVA-Cu-HVs can release OVA in a pH-responsive behavior and promote cytosolic release of antigen to enhance antigen cross-presentation. Immunization with OVA-Cu-HVs promotes the maturation of dendritic cells in draining lymph nodes, induces robust antigen-specific T lymphocyte response, and inhibits tumor growth in vivo. In addition, OVA-Cu-HVs are efficacious after being stored for 4 weeks at room temperature and are expected to simplify vaccine storage and lower the cost of cold storage for transportation. Looking forward, OVA-Cu-HVs may hold strong potential to be as an effective vaccine delivery platform, which will facilitate the application of organic-inorganic hybrid flowers in biomedical areas.

Chitosan/calcium phosphates nanosheet as a vaccine carrier for effective cross-presentation of exogenous antigens.

Chitosan/calcium phosphate nanosheet as a promising antigen carrier was prepared via the direct mixture of modified chitosan, PBS and CaCl2. Specifically, chitosan was modified with catechol groups, and its water solubility under neutral conditions was improved. Then, nanosheet was formed by mixing modified chitosan and PBS followed by addition of CaCl2. Antigen was entrapped into the nanosheet via coprecipitation during its preparation. The nanosheet composed of CaHPO4·2H2O crystals, was internalized by dendritic cells (DCs) via macropinocytosis with enhanced efficiency. The antigen endosomal escape induce by nanosheet was successful observed with intracellular Lysotracker and Lamp-1 staining. Moreover, DCs activation was triggered by the nanosheet along with the up-regulated expression of co-stimulation marker and production of Th1-type cytokines. More importantly, cross-presentation of antigens achieved by the nanosheet was markedly increased when compared to free antigen. Therefore, chitosan/calcium phosphate nanosheet could be used as a vaccine carrier for effective cross-presentation of exogenous antigens.

Coordination microparticle vaccines engineered from tumor cell templates.

A method for encapsulation of individual tumor cells with an epigallocatechin-3-gallate (EGCG)-Al(iii) coordination layer, which can be used as potential tumor vaccines, was developed. The interaction between microparticle vaccines and dendritic cells was investigated in vitro. The microparticles (∼10 µm) were efficiently internalized by DCs with enhanced uptake efficiency via actin polymerization and clathrin-mediated endocytosis.

Alum-functionalized graphene oxide nanocomplexes for effective anticancer vaccination.

Aluminum-based adjuvant (e.g., aluminum oxyhydroxide (AlO(OH), known as the commercial Alhydrogel® (Alum)) is the first adjuvant to be used in human vaccines. Although Alum shows a robust induction of antibody-mediated immunity, its weak stimulation of cell-mediated immunity makes it a questionable adjuvant for cancer immunotherapy. Herein, we described a novel formulation of Alum-based adjuvant by preparing AlO(OH)-modified graphene oxide (GO) nanosheets (GO-AlO(OH)), which, in addition to maintaining the induction of humoral immune response by AlO(OH), could further elicit the cellular immune response by GO. Similar to Alum, GO-AlO(OH) vaccine formulation could be constructed by the incorporation of antigen using a facile mixing/adsorption approach. Antigen-loaded GO-AlO(OH) nanocomplexes facilitated cellular uptake and cytosolic release of antigens and promoted DC maturation, thereby eliciting higher antigen-specific IgG titers, inducing robust CD4+ and CD8+ T lymphocyte response, and inhibiting tumor growth in vivo. Furthermore, by employing tumor cell lysate-based cancer vaccines, GO-AlO(OH) nanocomplexes led to significant inhibition of tumor growth and can be implemented as a personalized treatment strategy for cancer vaccine development. Overall, GO-AlO(OH) nanocomplexes described herein may serve as a facile and efficient approach for effective anticancer vaccination. STATEMENT OF SIGNIFICANCE: Herein, we described a novel formulation of aluminum-based adjuvant by preparing aluminum oxyhydroxide (AlO(OH)) (known as "Alum")-modified graphene oxide (GO) nanocomplexes (GO-AlO(OH)), which, in addition to maintaining the induction of humoral immune response by AlO(OH), could further elicit the cellular immune response by GO. GO-AlO(OH) nanocomplexes can be prepared easily and in large scale by a chemical precipitation method. Similar to "Alum," antigen-loaded GO-AlO(OH) vaccine formulation could be constructed by the incorporation of antigen using a facile mixing/adsorption approach. The very simple and reproductive preparation process of vaccines and the powerful ability to raise both humoral and cellular immune responses provide a novel approach for improving cancer immunotherapy efficacy.

A Generic Coordination Assembly-Enabled Nanocoating of Individual Tumor Cells for Personalized Immunotherapy.

A generic and effective tumor cells encapsulation strategy enabled by metal-organic coordination is developed to prepare a vaccine for personalized immunotherapy. Specifically, an epigallocatechin-3-gallate (EGCG)-Al(III) coordination layer is in situ formed onto individual living cells in aqueous phase and the process can be completed within an hour. 98% of proteins in the cells are entrapped within the microparticles, which are endowed with high antigens loading capacity. The microparticles enhance the uptake efficiency of antigens, protect antigens from degradation in vivo, and delay the retention time of antigens in the lymph nodes. Moreover, dendritic cells (DCs) activation is triggered by the microparticles, and simultaneously, the expression of costimulation marker on DCs and the production of Th1-related cytokines are significantly upregulated. Moreover, six kinds of tumor cells are utilized and successfully coated with the EGCG/Al(III) layer, suggesting the generalization of this strategy. More importantly, the microparticles exhibit a comparative antitumor effect with polyinosinic-polycytidylic acid (PolyI:C) in B16 pulmonary metastasis model. Overall, the encapsulation strategy enabled by metal-organic coordination can be potentially useful for personalized immunotherapy customized to individual patient's tumor cells.

Nanoscale Reduced Graphene Oxide-Mediated Photothermal Therapy Together with IDO Inhibition and PD-L1 Blockade Synergistically Promote Antitumor Immunity.

Despite the potential efficacy of immune checkpoint blockade for effective treatment of cancer, this therapeutic modality is not generally curative, and only a fraction of patients respond. Combination approaches provide strategies to target multiple antitumor immune pathways to induce synergistic antitumor immunity. Here, a multi-combination immunotherapy, including photothermal therapy (PTT), indoleamine-2,3-dioxygenase (IDO) inhibition, and programmed cell death-ligand 1 (PD-L1) blockade, is introduced for inducing synergistic antitumor immunity. We designed a multifunctional IDO inhibitor (IDOi)-loaded reduced graphene oxide (rGO)-based nanosheets (IDOi/rGO nanosheets) with the properties to directly kill tumor cells under laser irradiation and in situ trigger antitumor immune response. In vivo experiments further revealed that the triggered immune response can be synergistically promoted by IDO inhibition and PD-L1 blockade; the responses included the enhancement of tumor-infiltrating lymphocytes, including CD45+ leukocytes, CD4+ T cells, CD8+ T cells, and NK cells; the inhibition of the immune suppression activity of regulator T cells (Tregs); and the production of INF-γ. We also demonstrate that the three combinations of PTT, IDO inhibition, and PD-L1 blockade can effectively inhibit the growth of both irradiated tumors and tumors in distant sites without PTT treatment. This work can be thought of as an important proof of concept to target multiple antitumor immune pathways to induce synergistic antitumor immunity.

Photothermally Controlled MHC Class I Restricted CD8+ T-Cell Responses Elicited by Hyaluronic Acid Decorated Gold Nanoparticles as a Vaccine for Cancer Immunotherapy.

Cancer vaccines aim to induce a strong major histocompatibility complex class I (MHC-I)-restricted CD8+ cytotoxic T-cell response, which is an important prerequisite for successful cancer immunotherapy. Herein, a hyaluronic acid (HA) and antigen (ovalbumin, OVA)-decorated gold nanoparticle (AuNPs)-based (HA-OVA-AuNPs) vaccine is developed for photothermally controlled cytosolic antigen delivery using near-infrared (NIR) irradiation and is found to induce antigen-specific CD8+ T-cell responses. Chemical binding of thiolated HA and OVA to AuNPs facilitates antigen uptake of dendritic cells via receptor-mediated endocytosis. HA-OVA-AuNPs exhibit enhanced NIR absorption and thermal energy translation. Cytosolic antigen delivery is then permitted through the photothermally controlled process of local heat-mediated endo/lysosome disruption by laser irradiation along with reactive oxygen species generation, which helps to augment proteasome activity and downstream MHC I antigen presentation. Consequently, the HA-OVA-AuNPs nanovaccine can effectively evoke a potent anticancer immune response in mice under laser irradiation. This NIR-responsive nanovaccine is promising as a potent vaccination method for improving cancer vaccine efficacy.

Nanovaccine Incorporated with Hydroxychloroquine Enhances Antigen Cross-Presentation and Promotes Antitumor Immune Responses.

Induction of effective antigen-specific CD8+ T-cell responses is critical for cancer immunotherapy success. Hydroxychloroquine (HCQ) is a widely used classical antimalarial and antirheumatic drug. HCQ is also an endosomal membrane disrupting agent that can lead to vesicular swelling and membrane permeabilization, which likely facilitates the release of therapeutic agents from lysosomes into the cytoplasm. Here, we develop a minimalistic nanovaccine, which is composed of poly(lactide- co-glycolide)acid (PLGA) nanoparticles (NPs) encapsulating a physical mixture of ovalbumin (OVA, a model antigen) and HCQ (HCQ-OVA-PLGA NPs). We tested whether HCQ could spatiotemporally control the cytosolic delivery of antigens, enhance antigen processing and presentation via the major histocompatibility complex (MHC)-I pathway, and thus generate a sufficient antitumor cytotoxic T-cell response. The results of in vitro experiments showed that HCQ-OVA-PLGA NPs significantly enhanced OVA escape from lysosomes into the cytoplasm within bone-marrow-derived dendritic cells. We also observed that HCQ-OVA-PLGA NPs enhanced the expression level of MHC-I on dendritic cells and improved cross-presentation of antigen, compared to free OVA or OVA-PLGA NPs. Results of in vivo experiments confirmed that HCQ initiated Th1-type responses and strong CD8+ T-cell responses that induced tumor cell apoptosis. Moreover, vaccination of mice with HCQ-OVA-PLGA NPs effectively generated memory immune responses in vivo and prevented tumor progression. We conclude that co-encapsulation of HCQ with antigens in nanovaccines can boost antigen-specific antitumor immune responses, particularly through CD8+ T-cells, serving as a simple and effective platform for the treatment of tumors and infectious diseases.