Synergy of Immunostimulatory Genetherapy with Immune Checkpoint Blockade Motivates Immune Response to Eliminate Cancer

Normalizing the tumor-induced immune deficiency in the immunosuppressive tumor microenvironment (TME) through increasing the efficient infiltration and activation of antitumoral immunity in TME is the core of promising immunotherapy. Herein, a Cyclo(Arg-Gly-Asp-d -Phe-Lys) (RGD) peptides-modified combinatorial immunotherapy system based on the self-assembly of the nanoparticles named RGD-DMA composed of RGD-PEG-PLA, methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) and 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP) is used to codeliver the immunostimulatory chemokine CCL19-encoding plasmid DNA (CCL19 pDNA) and immune checkpoint ligand PD-L1 inhibitor (BMS-1). The RGD-DMA/pCCL19-BMS-1 system not only exhibited significant inhibition of tumor progression but also induced locally high concentrations of immunostimulatory cytokines at tumor sites without causing an obviously systemic inflammatory response. The immunosuppressive TME is efficaciously reshaped by the coadministration of RGD-DMA/pCCL19 and BMS-1, as indicated by the activated T lymphocytes, increased intratumoral-infiltration of mature dendritic cells (DCs), and the repolarization of macrophages from pro-tumoral M2-phenotype toward tumoricidal M1-phenotype. The upregulated PD-L1 expression at tumor sites caused by the increased IFN-γ levels after immunostimulatory gene therapy further demonstrated the synergistic effects of BMS-1 in counteracting the inhibitory role of PD-L1 expression in antitumor immunity. Therefore, the combination of immunostimulating therapy and immune checkpoint inhibitor that synergistically target multiple immune regulatory pathways demonstrates significant potential as a novel immunotherapy approach.     

Artificial Immunogenic Cell Death Lipid Nanoparticle Functions as a Therapeutic Vaccine for Cancer

Anticancer drug-mediated induction of immunogenic cell death (ICD) blocks metastasis or recurrence in cancer cells by promoting specific immune activity against cancer antigens. However, this strategy has failed to afford adequate treatment efficiency. Overcoming the failure of ICD-mediated cancer therapy, lipid nanoparticles (LNPs) containing cancer cell surface proteins are synthesized using sonication and extrusion without microfluidics. In addition, these LNPs are decorated with high-mobility group box 1 protein and calreticulin, indicators of ICD, and named artificial ICD LNPs (AiLNPs). Administration of AiLNPs effectively targets dendritic cells (DCs) and induces DC activation in mice. Moreover, treating CT-26 tumor-bearing mice with AiLNPs inhibits tumor growth by inducing CT-26 antigen-specific T-cell immunity. Furthermore, AiLNPs containing Lewis lung carcinoma (LLC1) membrane proteins can prevent metastatic LLC1 tumor growth in the lung via LLC1 antigen-specific T-cell activation. Finally, AiLNPs synthesized with human breast cancer membrane proteins activate DC-mediated antigen-specific T-cell immunity, effectively killing tumor cells. Therefore, AiLNPs are expected to be developed as a patient-specific cancer treatment to prevent cancer recurrence and metastasis.     

Copper Sulfide Nanoparticle-Redirected Macrophages for Adoptive Transfer Therapy of Melanoma

Adoptive cell therapy (ACT) has achieved landmark advances in treating cancer in clinic. Recent advances in ACT of macrophages engineered to express chimeric antigen receptors (CARs) have shown effectiveness in treating solid tumors. However, the CAR-macrophage therapy is dependent on tumor antigen recognition and gene editing methods. Herein, an adoptive macrophage therapy is presented through copper sulfide nanoparticle-regulation that exhibits substantial antitumor effect in melanoma-bearing mice, without the need for tumor antigen repertoire. Bone marrow derived macrophages (BMDMs) incubated with the nanoparticles promote the cellular production of reactive oxygen species (ROS) through dynamin-related protein 1 (Drp1)-mediated mitochodrial fission. The high intracellular ROS level directs BMDMs polarization toward M1 phenotype by classical IKK-dependent NF-κB activation. Moreover, the copper sulfide nanoparticle-stimulated BMDMs (CuS-MΦ) reduce the expression of programmed death-1 (PD-1) and exhibit enhanced phagocytic and digestive ability. Intratumoral transfer of CuS-MΦ significantly prolongs the median survival time of the tumor-bearing mice, remodels the tumor microenvironment, and elicits systemic antitumor immunity. These results suggest a cancer therapeutic approach of adoptively transferred macrophages through the induction of intracellular ROS with nanomaterials.     

Bone Marrow Dendritic Cells Derived Microvesicles for Combinational Immunochemotherapy against Tumor

Various types of cell can change the cytoskeleton and shed microvesicles (MVs) with biomimic properties as parent cells in response to stimuli. To take use of the drug package capability of MVs and the potent antigen presentation property of dendritic cells (DCs), DC‐derived antigenic MVs are constructed by priming DCs with tumor‐derived MVs and then encapsulating a chemotherapeutic drug during MVs shedding. This kind of MVs exhibit significant inhibition on melanoma tumor growth and metastasis. The MV‐encapsulated chemotherapeutics can induce direct cytotoxicity and immunogenic cell death in tumor cells. Moreover, a robust antitumor immunity is induced in both, the tumor‐draining lymph node and the tumor microenvironment as the infiltration and activation of T lymphocytes increases. This kind of MVs is further explored in a hepatic ascites model with remarkable prolonged overall survival of mice. More importantly, the MVs can extend the survival of 60% mice more than 150 d without ascites even after rechallenging the tumor twice. This study demonstrates that antigenic MVs with chemotherapeutics possess great potential in cancer immunochemotherapy.     

Macrophage-Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention

Macrophages are one of the most abundant non-malignant cells in the tumor microenvironment, playing critical roles in mediating tumor immunity. As important innate immune cells, macrophages possess the potential to engulf tumor cells and present tumor-specific antigens for adaptive antitumor immunity induction, leading to growing interest in targeting macrophage phagocytosis for cancer immunotherapy. Nevertheless, live tumor cells have evolved to evade phagocytosis by macrophages via the extensive expression of anti-phagocytic molecules, such as CD47. In addition, macrophages also rapidly recognize and engulf apoptotic cells (efferocytosis) in the tumor microenvironment, which inhibits inflammatory responses and facilitates immune escape of tumor cells. Thus, intervention of macrophage phagocytosis by blocking anti-phagocytic signals on live tumor cells or inhibiting tumor efferocytosis presents a promising strategy for the development of cancer immunotherapies. Here, the regulation of macrophage-mediated tumor cell phagocytosis is first summarized, followed by an overview of strategies targeting macrophage phagocytosis for the development of antitumor therapies. Given the potential off-target effects associated with the administration of traditional therapeutics (for example, monoclonal antibodies and small molecule inhibitors), the opportunity for nanomedicine in macrophage phagocytosis intervention is highlighted.     

罗非昔布对胃癌细胞上清液中培养的树突状细胞分化成熟和功能的影响

目的：从免疫学角度分析罗非昔布（Rofecoxib）抗癌作用的机制。方法：将人外周血分离的单核细胞加入含重组人粒细胞巨噬细胞集落刺激因子和重组人白细胞介素的培养液中,随机分为空白组（PBS培养液）,干预组（胃癌细胞上清液＋罗非昔布,150mg/L）,对照组（胃癌细胞上清液）使其分化为树突状细胞（denstritic cell,DC）。混合培养48h后,动态观察DC成熟过程中的形态学变化,流式细胞术检测DC成熟表型（CD40、CD80）,混合T淋巴细胞增殖反应检测DC功能。结果：与对照组比较,空白组、干预组DC的CD40、CD80表达明显在增加（P〈0.05）,T细胞增殖作用明显增强（P〈0.05）。结论：罗非昔布可通过促进DC成熟,并增加DC的免疫活性而发挥抗癌作用。     

Cationic Lipids-Mediated Dual-Targeting of Both Dendritic Cells and Tumor Cells for Potent Cancer Immunotherapy

Impaired antigen presentation either in dendritic cells (DCs) or tumor cells impedes the triggering of antitumor immunity or tumor cell killing, resulting in failures of multiple types of cancer immunotherapy. Herein, the strategy of using dual-targeting nanomedicines to simultaneously improve the presentation of tumor antigens by both DCs and tumor cells is proposed. It is shown that tuning of surface charge of nanoparticles (NPs) by incorporating different amounts of cationic lipids alters the in vivo NP tissue accumulation and cellular targeting profiles. NPs with moderately positive surface charge (≈20 mV) achieve efficient accumulation in tumors and lymph nodes and dual-targeting to both DCs and tumor cells. As a proof-of-concept demonstration, siRNA against YTH N6−methyladenosine RNA binding protein 1 (YTHDF1) is delivered by the dual-targeting NPs to inhibit excessive antigen degradation in both DCs and tumor cells. For DCs, YTHDF1 downregulation promotes tumor antigen cross-presentation and cross-priming of antigen-specific T cells. For tumor cells, it enhances the presentation of endogenous tumor antigens and hence improves both the recognition and killing of tumor cells by primed antigen-specific T cells. The dual-targeting nanomedicines generate efficient antitumor immunity.     

Polysaccharide Nanodonuts for Photochemotherapy-Amplified Immunogenic Cell Death to Potentiate Systemic Antitumor Immunity Against Hepatocellular Carcinoma

Immunotherapy shows great promise in the treatment of hepatocellular carcinoma (HCC), however, the low response rate of HCC patients to immunotherapy caused by inadequately immunogenic and immunosuppressive tumor microenvironment (TME) is a huge challenge. Herein, a donut-like multifunctional polysaccharide nanoplatform (GH-PID) is constructed from doxorubicin/aldehyde hyaluronan nanoring, indocyanine green/hydroxyethyl chitosan nanocomplex, and HCC-bitargeted galactosamine-hyaluronan conjugate via a facile self-assembly process. The GH-PID nanodonuts exhibit excellent HCC-targeted ability and synergetic photochemotherapy effect with a coefficient index of about 0.44. Moreover, near infrared laser-irradiated GH-PID nanodonuts show robust therapeutic efficacy in HCC mouse models by virtue of photochemotherapy-augmented immunogenic cell death (ICD) effect. The remarkable ICD in combination with programmed death-1 antibody efficiently eradicates primary tumors and inhibits distant tumor growth and lung metastasis of HCC by maturing dendritic cells, increasing CD8⁺ T cell infiltration, suppressing the expansion and trafficking of immunosuppressive myeloid-derived suppressor cells, and ameliorating immunosuppressive TME. This study provides a facile and versatile strategy to construct polysaccharide nanodonuts integrating multifunctionality and highly efficient HCC-targeted ability, and the nanodonuts-based ICD inducer holds great promise for potentiating systemic antitumor immunity and programmed death-1/programmed death-ligand 1 blockade efficacy.     

FAP-Targeted Photodynamic Therapy Mediated by Ferritin Nanoparticles Elicits an Immune Response against Cancer Cells and Cancer Associated Fibroblasts

Cancer-associated fibroblasts (CAFs) are present in many types of tumors and play a pivotal role in tumor progression and immunosuppression. Fibroblast-activation protein (FAP), which is overexpressed on CAFs, has been indicated as a universal tumor target. However, FAP expression is not restricted to tumors, and systemic treatment against FAP often causes severe side effects. To solve this problem, a photodynamic therapy (PDT) approach is developed based on ZnF₁₆Pc-loaded and FAP-specific single chain variable fragment (scFv)-conjugated apoferritin nanoparticles, or αFAP-Z@FRT. αFAP-Z@FRT PDT efficiently eradicates CAFs in tumors without inducing systemic toxicity. When tested in murine 4T1 models, the treatment elicits anti-cancer immunity, causing suppression of both primary and distant tumors, that is, the abscopal effect. Treatment efficacy is enhanced when αFAP-Z@FRT PDT is used in combination with anti-PD1 antibodies. Interestingly, it is found that the PDT treatment not only elicits a cellular immunity against cancer cells, but also stimulates an anti-CAFs immunity. This is supported by an adoptive cell transfer study, where T cells taken from 4T1-tumor-bearing animals treated with αFAP PDT retard the growth of A549 tumors established on nude mice. Overall, this approach is unique for permitting site-specific eradication of CAFs and inducing a broad spectrum anti-cancer immunity.     

Multiantigenic Nanoformulations Activate Anticancer Immunity Depending on Size

Nanoparticle‐adjuvanted cancer vaccines are attracting increasing attention because they can induce an effective anticancer immune response. Single‐antigen vaccines are inefficient to inhibit cancer progression due to the heterogeneity of tumors and the antigenicity alteration of tumor‐associated antigens. Therefore, the efficient delivery of multiple antigens to antigen‐presenting cells is an excellent opportunity for strong anticancer immunity. In this study, three immunoadjuvant‐loaded multiantigenic nanoparticles MANPs/R837 with different diameters, i.e., 83, 103, and 122 nm, are prepared through coating of the cancer cell membrane as a source of multiple antigens onto the imiquimod R837‐loaded poly(lactic‐co‐glycolic acid) nanoparticles. The MANP/R837 with a diameter of 83 nm (MANP83/R837) shows the most efficient delivery of the payload to the draining lymph nodes and achieves the best antigen presentation to T lymphocytes. Compared with the other two nanovaccines, MANP83/R837 has a stronger inhibitory effect on tumor growth and metastasis. In the combination therapy with checkpoint blockade therapy using programmed cell death‐1 antibody, MANPs/R837 show effective inhibition against tumor progression, and MANP83/R837 achieves the most exciting effect. Therefore, MANPs/R837, as a promising therapeutic cancer vaccine, demonstrates great prospects in cancer immunotherapy.     

Negatively Charged Magnetite Nanoparticle Clusters as Efficient MRI Probes for Dendritic Cell Labeling and In Vivo Tracking

Cell labeling and tracking via magnetic resonance imaging (MRI) has drawn much attention for its noninvasive property and longitudinal monitoring functionality. Employing of imaging probes with high labeling efficiency and good biocompatibility is one of the essential factors that determine the outcome of tracking. In this study, negatively charged superparamagnetic iron oxide (PAsp‐PCL/SPIO) nanoclusters are developed for dendritic cell (DC) labeling and tracking in vivo. PAsp‐PCL/SPIO has a diameter of 124 ± 41 nm in DLS, negatively charged surface (zeta potential = ?27 mV), and presents high T ₂ relaxivity (335.6 Fe mm ^?1 s^?1) and good DC labeling efficiency. Labeled DCs are unaffected in their viability, proliferation, and differentiation capacity, and have an excellent MR imaging sensitivity in vitro. To monitor the migration of DCs into lymphoid tissues in vivo, which will be related to the final immunotherapy results, T ₂‐wighted and T ₂‐map imaging of popliteal nodes at different points in time are acquired under a clinical 3 T scanner after subcutaneous injection of a certain number of labeled DCs at hindleg footpads of mice. The signal intensities decreasing and T ₂ values shortening of ipsilateral popliteal nodes are significant and display a time‐ and dose‐dependence, showing DCs' migration to the draining lymph nodes.     

An Integrated Nanoaircraft Carrier Modulating Antitumor Immunity to Enhance Immune Checkpoint Blockade Therapy

Immune checkpoint blockade (ICB) therapy revolutionizes cancer therapeutics. However, the effectiveness of ICB therapy is restricted. Focusing on the tumor itself and the immune system, an integrated nanoaircraft carrier that coloaded three therapeutic agents (NNG/OTC) to eradicate tumor cells, enhance T-cells intratumoral infiltration, and relieve the inhibition of tumor immunosuppressive microenvironment (TIM) is designed. First, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is used to combine with oxaliplatin for reducing tumor burden. Second, oxaliplatin is used to elicit immunogenic cell death and combine with cytosine-phosphate-guanine (CpG) to promote dendritic cells maturation, ultimately increasing T-cells intratumoral infiltration. Third, CpG is further used to repolarize M2 type of tumor-associated macrophages, thus reversing immunosuppression of TIM. The nanoaircraft carrier can effectively arrive at the tumor site and detach small-sized nanoparticles under a high concentration of matrix metalloproteinase-2, which promotes deep tumor penetration. Under the mediation of targeting ligands, three therapeutic agents loaded in small-sized nanoparticles could be launched to their target cells. NNG/OTC modulates the antitumor immunity and exhibits excellent tumor inhibition when in combination with ICB therapy, indicating the increased response of ICB therapy. Collectively, NNG/OTC can co-deliver various drugs with different physicochemical properties and provide a promising strategy for enhancing ICB therapy.     

Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy

The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro‐inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T‐cell (Treg) activation. Here, the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)‐b‐poly(propylene sulfide) copolymers to enhance the targeted modulation of DCs by transporting the anti‐inflammatory agent 1,25‐dihydroxyvitamin D3‐(aVD) and ApoB‐100‐derived antigenic peptide P210 are engineered. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P‐D2 peptide, which binds CD11c on the DC surface, significantly enhance the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Weekly low‐dose intravenous administration of DC‐targeted, aVD‐loaded polymersomes significantly inhibit atherosclerotic lesion development in high‐fat‐diet‐fed ApoE^?/? mice. The results validate the key role of DC immunomodulation during aVD‐dependent inhibition of atherosclerosis and demonstrate the therapeutic enhancement and dosage lowering capability of cell‐targeted nanotherapy in the treatment of CVD.     

Amphiphilic Poly(Amino Acid) Nanoparticles Induce Size‐Dependent Dendritic Cell Maturation

Size‐regulated amphiphilic poly(amino acid) nanoparticles (NPs) composed of poly(γ‐glutamic acid) (γ‐PGA) and the hydrophobic amino acid derivative, L ‐phenylalanine ethyl ester (Phe) are prepared to evaluate the effects of particle size on dendritic cell (DC) uptake of NPs and their immune stimulatory activities as delivery carriers and adjuvants. The size of the Phe‐conjugated γ‐PGA NPs (γ‐PGA–Phe NPs) is easily controlled by regulating the aggregated γ‐PGA–Phe numbers. Each of the differently sized γ‐PGA–Phe NPs could efficiently encapsulate ovalbumin (OVA), and the amount of encapsulated OVA per milligram of NPs is almost the same despite the differences in size. The DC uptake of small NPs is lower than for the larger NPs, but the effect of DC activation by NPs is high in the small sizes. The DC activation is significantly affected by the size of the NPs, which suggests that not only the uptake process of the NPs, but also the surface interactions between the NPs and DCs, is important for the induction of DC maturation. The precisely size‐controllable γ‐PGA–Phe NPs have significant potential as an antigen carrier and vaccine adjuvant. These results should provide guidelines for adjuvant design in the development of an effective vaccine.     

MRAM Cell Technology for Over 500-MHz SoC

This paper describes newly developed magnetic random access memory (MRAM) cell technology suitable for high-speed memory macros embedded in next-generation system LSIs: a two-transistor one-magnetic tunneling junction (2T1MTJ) cell structure, a write-line-inserted MTJ, and a 5T2MTJ cell structure. The 2T1MTJ cell structure makes it possible to significantly improve the write margin and accelerate the operating speed to 200 MHz. Its high compatibility with SRAM specifications and its wide write margin were confirmed by measuring 2T1MTJ MRAM test chips. Although the cell structure requires a small-writing-current MTJ, the current can be reduced to 1mA using the newly developed write-line-inserted MTJ. Further development to reduce the current down to 0.5 mA is required to obtain a cell area of 1.9 mum², which is smaller than the SRAM cell area, in the 0.13-mum CMOS process. The 5T2MTJ cell structure also enables random-access operation over 500 MHz because the sensing signal is amplified in each cell. Random access time of less than 2 ns can be achieved with SPICE simulation when the magnetic resistance is 5 kOmega and the magnetoresistive (MR) ratio is more than 70%     

树突状细胞分化模型在人工免疫系统中的应用研究

 树突状细胞(Dendritic Cell,DC)是先天性免疫系统的重要组件,其分化机制是正确引发与调节适应性免疫响应的关键.首先,在描述DC分化的生物机理基础上,抽象出了DC的信息处理过程.其次,在阐释DAMP等四类外部信号的含义与功能、信号融合过程的基础上,定义了未成熟、完全成熟与半成熟DC Agent,刻画了它们的分化数学模型与演化过程.最后,论证了各类DC Agent数量与生存周期之间的关系.实验结果表明DC分化机制对降低入侵检测误报率、实现自我调节和进一步增强计算机系统安全具有重要的理论意义与应用价值.     

Cancer Cell Membrane‐Coated Nanoparticles for Personalized Therapy in Patient‐Derived Xenograft Models

Cell membrane coating nanotechnology, which endows nanoparticles with unique properties, displays excellent translational potential in cancer diagnosis and therapy. However, the preparation and evaluation of these cell membrane‐coated nanoparticles are based on cell lines and cell‐line‐based xenograft mouse models. The feasibility of cell membrane‐camouflaged nanomaterials is tested in a preclinical setting. Head and neck squamous cell carcinoma (HNSCC) patient‐derived tumor cell (PDTC) membranes are coated onto gelatin nanoparticles (GNPs) and the resulting PDTC@GNPs show efficient targeting to homotypic tumor cells and tissues in patient‐derived xenograft (PDX) models. When the donor‐derived cell membrane of PDTC@GNPs matched those of the host cells, significant targeting capability is observed. In contrast, mismatch between the donor and host results in weak targeting. Furthermore, it is demonstrated that autologous separation and administration of cellular membranes and anticancer cisplatin (Pt)‐loaded PDTC@GNPs, respectively, lead to almost complete tumor ablation in a subcutaneous model and effectively inhibit tumor recurrence in a postsurgery model. The work presented here reinforces the translation of these biomimetic nanoparticles for clinical applications and offers a simple, safe, and effective strategy for personalized cancer treatment.     

趋化因子配体18与鼻咽癌相关性研究及意义

目的：探讨趋化因子配体18（CCL18）在鼻咽癌患者血浆中的表达水平及检测在体外对人鼻咽癌细胞株增殖和迁移能力的影响。方法：收集到重庆医科大学附属第二医院就诊并病理诊断为鼻咽癌患者37例,在未接受任何治疗前留取血液标本,另取20例健康体检者外周血液标本作为正常人群对照。以酶联免疫吸附测定（ELIAS）方法检测血浆中CCL18的表达水平。体外实验以人鼻咽癌细胞株HNE-1为研究对象,用噻唑蓝（MTT）比色法检测重组CCL18对细胞增殖能力的影响,用Transwe11体外迁移系统检测CCL18对鼻咽癌细胞的趋化作用。结果：鼻咽癌患者血浆中CCL18的表达水平明显高于健康体检者（P〈0．0001）,伴有颈部淋巴结转移的鼻咽癌患者较未发生颈部淋巴结转移者血浆中CCL18的表达水平显著升高（P〈0．05）。CCL18因子在体外对鼻咽癌细胞无明显促进增殖作用（P〉0．05）。CCL18对鼻咽癌细胞具有明显促进迁移趋化作用,并呈现浓度依赖性。结论：CCL18是鼻咽癌的生物学标志物,其表达与鼻咽癌的侵袭转移相关,对鼻咽癌的诊断和预后判断有一定临床意义。     

Myeloid‐Derived Suppressor Cell Membrane‐Coated Magnetic Nanoparticles for Cancer Theranostics by Inducing Macrophage Polarization and Synergizing Immunogenic Cell Death

A major challenge for traditional cancer therapy, including surgical resection, chemoradiotherapy, and immunotherapy, is how to induce tumor cell death and leverage the host immune system at the same time. Here, a myeloid‐derived suppressor cell (MDSC) membrane‐coated iron oxide magnetic nanoparticle (MNP@MDSC) to overcome this conundrum for cancer therapy is developed. In this study, MNP@MDSC demonstrates its superior performance in immune evasion, active tumor‐targeting, magnetic resonance imaging, and photothermal therapy (PTT)‐induced tumor killing. Compared with red blood cell membrane‐coated nanoparticles (MNPs@RBC) or naked MNPs, MNP@MDSCs are much more effective in active tumor‐targeting, a beneficial property afforded by coating MNP with membranes from naturally occurring MDSC, thus converting the MNP into “smart” agents that like to accumulate in tumors as the source MDSCs. Once targeted to the tumor microenvironment, MNPs@MDSC can act as a PTT agents for enhanced antitumor response by inducing immunogenic cell death, reprogramming the tumor infiltrating macrophages, and reducing the tumor's metabolic activity. These benefits, in combination with the excellent biocompatibility and pharmacological kinetics characteristics, make MNP@MDSC a promising, multimodal agent for cancer theranostics.