Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer.

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.

Engineering Nanoscale Artificial Antigen-Presenting Cells by Metabolic Dendritic Cell Labeling to Potentiate Cancer Immunotherapy.

Nanoscale artificial antigen-presenting cells (aAPCs) are promising to activate T cells directly for cancer immunotherapy, while feasible and flexible strategy to develop nanoscale aAPCs remains highly desirable. Metabolic glycoengineering is used to decorate chemical tags on cells which enables bioorthogonal chemical conjugation of functional molecules. Herein, we develop a nanoscale aAPC by metabolic dendritic cell (DC) labeling to mobilize T-cell based antitumor immunity. We coat azido-labeled DC membrane on imiquimod-loaded polymeric nanoparticles and sequentially modify anti-CD3ε antibody via click chemistry. The nanoscale aAPCs perform improved distribution in lymph nodes and stimulate T cells and resident APCs. Significant inhibition of tumor inoculation and growth is observed after the vaccination, which can be further improved by combining antiprogrammed cell death receptor 1 (PD1) therapy. Our results demonstrate the promising application of metabolically labeled DCs for designing nanoscale aAPCs, which provide a simple and general strategy to potentiate cancer immunotherapy.

Smart Nanosized Drug Delivery Systems Inducing Immunogenic Cell Death for Combination with Cancer Immunotherapy.

Cancer immunotherapy, which suppresses tumor relapse and metastasis by boosting host immunity and inducing long-term immune memory effects, is emerging as a vital approach to improve the prognosis of patients. Although remarkable efficacy has been observed in some patients, challenges including low response rate, drug resistance, and immune-related adverse effects still limit the clinical application of cancer immunotherapy in broad types of tumors. Immunotherapeutic agents are used to enhance tumor immunogenicity and reverse the effects of the immunosuppressive tumor microenvironment (ITM), but the benefits of monotherapy are mild and transient due to off-target distribution of drugs. To overcome these issues, smart nanosized drug delivery systems (sNDDS) have been developed to enhance tissue specificity, co-deliver multiple drugs, prime immune cells, and amplify immune responses in tumors. Moreover, accumulating knowledge in cancer biology, immunology, and material science has also greatly promoted the development of sNDDS for enhancing cancer immunotherapy.In this Account, we will discuss the approaches of our group in designing sNDDS to induce immunogenic cell death (ICD) for combination with cancer immunotherapy. We propose a brief overview on the design of nanocarriers, intelligent moieties and immunotherapeutic agents in sNDDS. Then, we discuss the strategies to remodel ITM by leveraging ICD as well as cooperating with programmed cell death protein 1 ligand blockade and indoleamine 2,3-dioxygenase 1 inhibition. We have synthesized a series of stimuli-responsive polymers and prodrugs to fabricate sNDDS and have integrated multiple immunotherapeutic drugs into one platform for combinational immunotherapy. Last, we present an outlook on future design of sNDDS and possible directions for enhancing cancer immunotherapy. Building on the concept of enhancing tumor immunogenicity and reversing ITM, we hope this Account will contribute to the rational design of sNDDS for co-delivery of multiple drugs with amplified immunotherapeutic efficacy.

Engineering Polymeric Prodrug Nanoplatform for Vaccination Immunotherapy of Cancer.

Neoantigen-based cancer vaccines are promising for boosting cytotoxic T lymphocyte (CTL) responses. However, the therapeutic effect of cancer vaccines is severely blunted by functional suppression of the dendritic cells (DCs). Herein, we demonstrated an acid-responsive polymeric nanovaccine for activating the stimulator of interferon genes (STING) pathway and improving cancer immunotherapy. The nanovaccines were fabricated by integrating an acid-activatable polymeric conjugate of the STING agonist and neoantigen into one single nanoplatform. The nanovaccines efficiently accumulated at the lymph nodes for promoting DC uptake and facilitating cytosol release of the neoantigens. Meanwhile, the STING agonist activated the STING pathway in the DCs to elicit interferon-ß secretion and to boost T-cell priming with the neoantigen. The nanovaccine dramatically inhibited tumor growth and occurrence of B16-OVA melanoma and 4T1 breast tumors in immunocompetent mouse models. Combination immunotherapy with the nanovaccines and anti-PD-L1 antibody demonstrated further improved antitumor efficacy in a 4T1 breast tumor model.

Non-viral gene delivery for cancer immunotherapy.

Recent decades have witnessed the revolutionary development of cancer immunotherapies, which boost cancer-specific immune responses for long-term tumor regression. However, immunotherapy still has limitations, including off-target side effects, long processing times and limited patient responses. These disadvantages of current immunotherapy are being addressed by improving our understanding of the immune system, as well as by establishing combinational approaches. Advanced biomaterials and gene delivery systems overcome some of these delivery issues, harnessing adverse effects and amplifying immunomodulatory effects, and are superior to standard formulations with respect to eliciting antitumor immunity. Nucleic acid-based nanostructures have diverse functions, ranging from gene expression and gene regulation to pro-inflammatory effects, as well as the ability to specifically bind different molecules. A brief overview is provided of the recent advances in the non-viral gene delivery methods that are being used to activate cancer-specific immune responses. Furthermore, the tumor microenvironment-responsive synergistic strategies that modulate the immune response by targeting various signaling pathways are discussed. Nanoparticle-based non-viral gene delivery strategies have great potential to be implemented in the clinic for cancer immunotherapy.

Acidity-Triggered Ligand-Presenting Nanoparticles To Overcome Sequential Drug Delivery Barriers to Tumors.

The success of cancer chemotherapy is impeded by poor drug delivery efficiency due to the existence of a series of pathophysiological barriers in the tumor. In this study, we reported a tumor acidity-triggered ligand-presenting (ATLP) nanoparticle for cancer therapy. The ATLP nanoparticles were composed of an acid-responsive diblock copolymer as a sheddable matrix and an iRGD-modified polymeric prodrug of doxorubicin (iPDOX) as an amphiphilic core. A PEG corona of the polymer matrix protected the iRGD ligand from serum degradation and nonspecific interactions with the normal tissues while circulating in the blood. The ATLP nanoparticles specifically accumulated at the tumor site through the enhanced permeability and retention (EPR) effect, followed by acid-triggered dissociation of the polymer matrix within the tumoral acidic microenvironment (pH ∼ 6.8) and subsequently exposing the iRGD ligand for facilitating tumor penetration and cellular uptake of the PDOX prodrug. Additionally, the acid-triggered dissociation of the polymer matrix induced a 4.5-fold increase of the fluorescent signal for monitoring nanoparticle activation in vivo. Upon near-infrared (NIR) laser irradiation, activation of Ce6-induced significant reactive oxygen species (ROS) generation, promoted drug diffusion inside the tumor mass and circumvented the acquired drug resistance by altering the gene expression profile of the tumor cells. The ATLP strategy might provide a novel insight for cancer nanomedicine.

Smart nanoparticles improve therapy for drug-resistant tumors by overcoming pathophysiological barriers.

The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have several advantages over the free drug forms, including reduced cytotoxicity, prolonged circulation in the blood and increased accumulation in tumors. Currently, however, nanoparticulate drugs have only marginally improved the overall survival rate in clinical trials because of the various pathophysiological barriers that exist in the tumor microenvironment, such as intratumoral distribution, penetration and intracellular trafficking, etc. Smart NPs with stimulus-adaptable physico-chemical properties have been extensively developed to improve the therapeutic efficacy of nanomedicine. In this review, we summarize the recent advances of employing smart NPs to treat the drug-resistant tumors by overcoming the pathophysiological barriers in the tumor microenvironment.

Acid-Activatable Versatile Micelleplexes for PD-L1 Blockade-Enhanced Cancer Photodynamic Immunotherapy.

Photodynamic therapy (PDT) has emerged as a promising clinical modality for cancer therapy due to its ability to initiate an antitumor immune response. However, PDT-mediated cancer immunotherapy is severely impaired by tumor-cell immunosuppression of host T cell antitumor activity through the programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) (PD-L1-PD-1) immune checkpoint pathway. Here, we demonstrate that PDT-mediated cancer immunotherapy can be augmented by PD-L1 knockdown (KD) in tumor cells. We rationally designed a versatile micelleplex by integrating an acid-activatable cationic micelle, photosensitizer (PS), and small interfering RNA (siRNA). The micelleplex was inert at physiological pH conditions and activated only upon internalization in the acidic endocytic vesicles of tumor cells for fluorescence imaging and PDT. Compared to PDT alone, the combination of PDT and PD-L1 KD showed significantly enhanced efficacy for inhibiting tumor growth and distant metastasis in a B16-F10 melanoma xenograft tumor model. These results suggest that acid-activatable micelleplexes utilizing PDT-induced cancer immunotherapy are more effective when combined with siRNA-mediated PD-L1 blockade. This study could provide a general strategy for enhancing the therapy efficacy of photodynamic cancer therapy.

Cooperative Treatment of Metastatic Breast Cancer Using Host-Guest Nanoplatform Coloaded with Docetaxel and siRNA.

Conventional chemotherapy shows moderate efficiency against metastatic cancer since it targets only part of the mechanisms regulating tumor growth and metastasis. Here, gold nanorod (GNR)-based host-guest nanoplatforms loaded with docetaxel (DTX) and small interfering RNA (siRNA)-p65 (referred to as DTX-loaded GNR (GDTX)/p65) for chemo-, RNA interference (RNAi), and photothermal ablation (PTA) cooperative treatment of metastatic breast cancer are reported. To prepare the nanoplatform, GNRs are first coated with cyclodextrin (CD)-grafted polyethylenimine (PEI) and then loaded with DTX and siRNA through host-guest interaction with CD and electrostatic interaction with PEI, respectively. Upon near-infrared laser irradiation, GNRs generate a significant hyperthermia effect to trigger siRNA and DTX release. DTX reduces tumor growth by inhibiting mitosis of cancer cells. Meanwhile, siRNA-p65 suppresses lung metastasis and proliferation of cancer cells by blocking the nuclear factor kappa B (NF-κB) pathway and downregulating the downstream genes matrix metalloproteinase-9 (MMP-9) and B cell lymphoma-2 (Bcl-2). It is demonstrated that GDTX/p65 in combination with laser irradiation significantly inhibits the growth and lung metastasis of 4T1 breast tumors. The antitumor results suggest promising potential of the host-guest nanoplatform for combinational treatment of metastatic cancer by using RNAi, chemotherapy, and PTA.

Versatile biomimetic nanomedicine for treating cancer and inflammation disease.

Nanosized drug delivery systems (NDDSs) have emerged as a powerful tool to optimize drug delivery in complex diseases, including cancer and inflammation. However, the therapeutic effect of NDDSs is still far from satisfactory due to their poor circulation time, low delivery efficiency, and innate toxicity. Fortunately, biomimetic approaches offer new opportunities to develop nanomedicine, which is derived from a variety of native biomolecules including cells, exosomes, bacteria, and so on. Since inheriting the superior biocompatibility and versatile functions of natural materials, biomimetic nanomedicine can mimic biological processes, prolong blood circulation, and lower immunogenicity, serving as a desired platform for precise drug delivery for treating cancer and inflammatory disease. In this review, we outline recent advances in biomimetic NDDSs, which consist of two concepts: biomimetic exterior camouflage and bioidentical molecule construction. We summarize engineering strategies that further functionalized current biomimetic NDDSs. A series of functional biomimetic NDDSs created by our group are introduced. We conclude with an outlook on remaining challenges and possible directions for biomimetic NDDSs. We hope that better technologies can be inspired and invented to advance drug delivery systems for cancer and inflammation therapy.

Smart drug delivery systems to overcome drug resistance in cancer immunotherapy.

Cancer immunotherapy, a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity, is currently an important clinical strategy for cancer treatment; however, tumors can develop drug resistance to immune surveillance, resulting in poor response rates and low therapeutic efficacy. In addition, changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents. Furthermore, tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction. To address these challenges, smart drug delivery systems (SDDSs) have been developed to overcome tumor cell resistance to immunomodulators, restore or boost immune cell activity, and magnify immune responses. To combat resistance to small molecules and monoclonal antibodies, SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells, thus increasing the drug concentration at the target site and improving efficacy. Herein, we discuss how SDDSs overcome drug resistance during cancer immunotherapy, with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment. SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented. Finally, we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy. We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.

Blocking Cholesterol Metabolism with Tumor-Penetrable Nanovesicles to Improve Photodynamic Cancer Immunotherapy.

Photodynamic therapy (PDT)-mediated cancer immunotherapy is attenuated due to the dysfunction of T cells in immunosuppressive tumor microenvironment (TME). Cholesterol metabolism plays a vital role in T cell signaling and effector. While the metabolic fitness of tumor infiltrating CD8+ T cells is impaired by nutrition restriction in TME and accumulated metabolites by tumor cells. Here a matrix metalloproteinase-2-sensitive tumor-penetrable nanovesicle is designed to regulate cholesterol metabolism pathway for enhancing photodynamic cancer immunotherapy. The nanovesicles accumulate in tumor and release internalizing RGD to promote deep penetration. Released avasimibe from the nanovesicles simultaneously blocks cholesterol metabolism in CD8+ T and tumor cells, thus reinvigorating the functions of T cells and suppressing the migration of tumor cells. Immune responses induced by PDT-triggered immunogenic cell death are further improved with cholesterol metabolism blockage. Compared with PDT alone, the designed nanovesicles display enhanced tumor growth inhibition in B16-F10 mouse tumor model. The approach provides an alternative strategy to improve photodynamic cancer immunotherapy by cholesterol metabolism intervention.

STING agonist-boosted mRNA immunization via intelligent design of nanovaccines for enhancing cancer immunotherapy.

Messenger RNA (mRNA) vaccine is revolutionizing the methodology of immunization in cancer. However, mRNA immunization is drastically limited by multistage biological barriers including poor lymphatic transport, rapid clearance, catalytic hydrolysis, insufficient cellular entry and endosome entrapment. Herein, we design a mRNA nanovaccine based on intelligent design to overcome these obstacles. Highly efficient nanovaccines are carried out with machine learning techniques from datasets of various nanocarriers, ensuring successful delivery of mRNA antigen and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) to targets. It activates stimulator of interferon genes (STING), promotes mRNA-encoded antigen presentation and boosts antitumour immunity in vivo, thus inhibiting tumour growth and ensuring long-term survival of tumour-bearing mice. This work provides a feasible and safe strategy to facilitate STING agonist-synergized mRNA immunization, with great translational potential for enhancing cancer immunotherapy.

Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells.

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

Light-controllable charge-reversal nanoparticles with polyinosinic-polycytidylic acid for enhancing immunotherapy of triple negative breast cancer.

Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.

Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry.

Bioorthogonal chemistry reactions occur in physiological conditions without interfering with normal physiological processes. Through metabolic engineering, bioorthogonal groups can be tagged onto cell membranes, which selectively attach to cargos with paired groups via bioorthogonal reactions. Due to its simplicity, high efficiency, and specificity, bioorthogonal chemistry has demonstrated great application potential in drug delivery. On the one hand, bioorthogonal reactions improve therapeutic agent delivery to target sites, overcoming off-target distribution. On the other hand, nanoparticles and biomolecules can be linked to cell membranes by bioorthogonal reactions, providing approaches to developing multi-functional drug delivery systems (DDSs). In this review, we first describe the principle of labeling cells or pathogenic microorganisms with bioorthogonal groups. We then highlight recent breakthroughs in developing active targeting DDSs to tumors, immune systems, or bacteria by bioorthogonal chemistry, as well as applications of bioorthogonal chemistry in developing functional bio-inspired DDSs (biomimetic DDSs, cell-based DDSs, bacteria-based and phage-based DDSs) and hydrogels. Finally, we discuss the difficulties and prospective direction of bioorthogonal chemistry in drug delivery. We expect this review will help us understand the latest advances in the development of active targeting and multi-functional DDSs using bioorthogonal chemistry and inspire innovative applications of bioorthogonal chemistry in developing smart DDSs for disease treatment.

Walking Dead Tumor Cells for Targeted Drug Delivery Against Lung Metastasis of Triple-Negative Breast Cancer.

Lung metastasis is challenging in patients with triple-negative breast cancer (TNBC). Surgery is always not available due to the dissemination of metastatic foci and most drugs are powerless because of poor retention at metastatic sites. TNBC cells generate an inflamed microenvironment and overexpress adhesive molecules to promote invasion and colonization. Herein, "walking dead" TNBC cells are developed through conjugating anti-PD-1 (programmed death protein 1 inhibitor) and doxorubicin (DOX)-loaded liposomes onto cell corpses for temporal chemo-immunotherapy against lung metastasis. The walking dead TNBC cells maintain plenary tumor antigens to conduct vaccination effects. Anti-PD-1 antibodies are conjugated to cell corpses via reduction-activated linker, and DOX-loaded liposomes are attached by maleimide-thiol coupling. This anchor strategy enables rapid release of anti-PD-1 upon reduction conditions while long-lasting release of DOX at inflamed metastatic sites. The walking dead TNBC cells improve pulmonary accumulation and local retention of drugs, reprogram the lung microenvironment through damage-associated molecular patterns (DAMPs) and PD-1 blockade, and prolong overall survival of lung metastatic 4T1 and EMT6-bearing mice. Taking advantage of the walking dead TNBC cells for pulmonary preferred delivery of chemotherapeutics and checkpoint inhibitors, this study suggests an alternative treatment option of chemo-immunotherapy to augment the efficacy against lung metastasis.

Engineering autologous tumor cell vaccine to locally mobilize antitumor immunity in tumor surgical bed.

Autologous tumor cell-based vaccines (ATVs) are emerging as a transformable approach for personalized immunotherapy, but their therapeutic efficacy remains unsatisfying in patients with cancer. Here, we design a photodynamic therapy (PDT)-motivated ATV (P-ATV) in Fmoc-KCRGDK-phenylboronic acid (FK-PBA) hydrogel, which mobilizes local immune activation to inhibit relapse of postoperative tumors. The FK-PBA targeting overexpressed sialic acid on tumor cells can enable on-demand gelation in residue tumor areas and maintain continuous vaccination in surgical bed. Unlike neoantigen-based vaccine or adoptive cell therapy that takes several months to prepare, P-ATV can be easily manufactured within a few days and efficiently boost neoepitope-specific CD8+ T cells to activate personalized immunotherapy. This simple and powerful approach of engineered ATVs provides an alternative strategy for personalized immunotherapy and is readily transformable to various kinds of cell-based antigens to inhibit the relapse of postoperative tumors.

Engineering Stimuli-Activatable Boolean Logic Prodrug Nanoparticles for Combination Cancer Immunotherapy.

Prodrug nanoparticles that codeliver the immune modulators to the tumor site are highly recommendable for cancer immunotherapy yet remain challenging. However, effective stimuli-responsive strategies that exploit the endogenous hallmarks of the tumor have paved the way for cancer immunotherapy. For the first time, the development of the Boolean logic prodrug nanoparticles (BLPNs) for tumor-targeted codelivery of immune modulators (e.g., immune activator and immune inhibitor) and combination immunotherapy is reported herein. A library of stimuli-activatable BLPNs is fabricated yielding YES/AND logic outputs by adjusting the input combinations, including extracellular matrix metalloproteins 2/9 (MMP-2/9), intracellular acidity (pH = 5.0-6.0), and reduction (glutathione) in the tumor microenvironment. Tunable and selective control over BLPNs dissociation and prodrug activation is achieved by specifying the connectivity of orthogonal stimuli-labile spacers while exploiting the endogenous signals at the tumor sites. The tumor-specific distribution of the BLPNs and stimuli-activation of the immune modulators for highly efficient cancer immunotherapy are further demonstrated. The results reported in this study may open a new avenue for tumor-specific delivery of immune therapeutics and precise cancer immunotherapy.

Improving Cancer Vaccine Efficiency by Nanomedicine.

Cancer vaccines, which have been widely investigated in the past few decades, are one of the most attractive strategies for cancer immunotherapy. Through the precise delivery of antigens and adjuvants to lymphoid organs or lymphocytes via nanotechnology, innate and adaptive immunity can be boosted to prevent the growth and relapse of malignant tumors. Indeed, nanomedicine offers great opportunities to improve the efficiency of vaccines. Various functional platforms are used to deliver small molecules, peptides, nucleic acids, and even whole cell antigens to the target area of interest, achieving enhanced antitumor immunity and durable therapeutic benefits. Herein, the recent progress in cancer vaccines based on nanotechnology is summarized. Novel platforms used for delivering tumor antigens, promoting adjuvant functions, and combining other therapeutic strategies are discussed. Moreover, possible striving directions and major challenges of nanomedicine for vaccination are also reviewed.