The immunomodulatory effects and excellent tolerability of polysaccharides make them optimal candidates for pulmonary vaccine adjuvants. Yet, the structure-immunostimulatory activity relationship of polysaccharides remains unrevealed. Here, we developed nanovaccines decorated with four polysaccharides of distinct structures─hyaluronic acid (HA), pectin (PC), chondroitin sulfate (SC), and heparan sulfate (SH)─all sharing similar particle sizes and zeta potential. Polysaccharides containing sulfate groups (SC, SH) exhibited superior efficacy in overcoming natural inhalation barriers and recruiting dendritic cells (DC). DC stimulation assays revealed that HA and SH significantly upregulated the expression of costimulation signals, with IL-6 secretion rising over 8.7-fold compared to pure OVA. Fluorescence resonance energy transfer demonstrated their detachment within the lysosomal microenvironment, thereby enhancing antigen cross-presentation. However, in vivo findings only showed that SH upregulated CCR7 chemokine and swiftly migrated to lymph nodes. Molecular docking and Western blot analyses further elucidated the involvement of the TLR─MyD88─TRAF6─NF-κB/MAPK/IRF-7 signaling pathways. Notably, SH-modified nanovaccines induced a more robust cellular and humoral immune response with the potential for immune memory. This study confirms that sulfate groups in polysaccharides enhance immune activation and that combining sulfate with acetyl groups offers a promising adjuvant configuration for augmenting mucosal, cellular, and humoral immunity.

The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NPFeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H2S amplification. The bioactive NPFeS/GD exhibited controlled release of GSDMD plasmid, H2S, and Fe2+ in response to the tumor microenvironment. Fe2+, H2S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H2S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NPFeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H2S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment.

The cancer-associated fibroblasts (CAFs) in tumor stroma present substantial barriers to drug penetration, resulting in tumor resistance and progression. One promising strategy is to reprogram CAFs into a quiescent state, which necessitates novel approaches. Our study introduces a sequential treatment strategy using chitosan thermosensitive hydrogels loaded with α-Mangostin (α-M), a small molecule drug with antifibrotic properties, aimed at reprogramming CAFs within the breast cancer tumor microenvironment (TME). We developed glutathione (GSH)-responsive nanoparticles (NPc) that carry the chemotherapeutic drug doxorubicin (DOX). Treatment with α-M results in the downregulation of CAF-specific biomarkers and a remodeled TME, which improves the penetration of NPc/DOX deep into the tumor tissue. This strategy holds great promise in enhancing cancer therapeutic outcomes in tumors rich in CAFs, particularly in the case of breast cancer.

The tumor microenvironment, characterized by hypoxia, supports the efficacy of anaerobic bacteria like attenuated S. typhimurium in cancer therapies. These bacteria target and penetrate deep tumor regions, significantly reducing tumor size but often lead to tumor regrowth due to limited long-term efficacy. To enhance the therapeutic impact, a novel biohybrid system, S@UIL, has been developed by coating S. typhimurium with a zirconium-based nanoscale metal-organic framework (UiO-66-NH2) loaded with indocyanine green (ICG) and luteolin (LUT). This system maintains the bacteria's tumor-targeting ability while increasing the penetration and therapeutic effectiveness through excessive autophagy and mild hyperthermia. In a subcutaneous colon cancer model, the integration of LUT and ICG promotes autophagic cell death and photothermal sensitization, leading to the release of damage-associated molecular patterns (DAMPs). These DAMPs activate immune responses through dendritic cells and T-cells, enhancing immunogenic cell death (ICD) and potentially reducing immune evasion by tumors. This single-administration approach also integrates multimodal imaging capabilities, providing a promising strategy for improved tumor ICD induction and cancer progression inhibition.

T-cell receptor (TCR) sequencing provides a novel platform for insight into and characterization of intricate T-cell profiles, advancing the understanding of tumor immune heterogeneity. Recently, transarterial chemoembolization (TACE) combined with systemic therapy has become the recommended regimen for advanced hepatocellular carcinoma. The regulation of the immune microenvironment after TACE and its impact on tumor progression and recurrence has been a focus of research. By examining and tracking fluctuations in the TCR repertoire following combination treatment, novel perspectives on the modulation of the tumor microenvironment post-TACE and the underlying mechanisms governing tumor progression and recurrence can be gained. Clarifying the distinctive metrics and dynamic alterations of the TCR repertoire within the context of combination therapy is imperative for understanding the mechanisms of anti-tumor immunity, assessing efficacy, exploiting novel treatments, and further advancing precision oncology in the treatment of hepatocellular carcinoma. In this review, we initially summarized the fundamental characteristics of TCR repertoire and depicted immune microenvironment remodeling after TACE. Ultimately, we illustrated the prospective applications of TCR repertoires in TACE combined with systemic therapy.

To develop next-generation metal-based drugs and dual-drug combination therapy for cancer, we proposed to develop a copper (Cu) complex that exerts anticancer function by integrating chemotherapy, immunotherapy and catalyzes a click reaction for the in situ synthesis of a chemotherapeutic agent, thereby achieving targeted dual-agent combination therapy. We designed and synthesized a tetranuclear Cu(I) complex (Cu4) with remarkable cytotoxicity and notable catalytic ability for the in situ synthesis of a chemotherapeutic agent via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC). We also constructed an apoferritin (AFt)-Cu4 nanoparticles (NPs) delivery system. Aft-Cu4 NPs not only showed an enhanced performance of tumor growth inhibition, but also improved the targeting ability and reduced the systemic toxicity of Cu4 in vivo. Importantly, the anticancer effect was enhanced by combining the Aft-Cu4 NPs with the resveratrol analogue obtained from the CuAAC reaction in situ. Finally, we revealed the anticancer mechanism of the Cu4/Aft-Cu4 NPs, which involves both cuproptosis and cuproptosis-induced systemic immune response.

Breast cancer, a prevalent disease with significant mortality rates, often presents treatment challenges due to its complex genetic makeup. This review explores the potential of combining Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene knockout strategies with immunotherapeutic approaches to enhance breast cancer treatment. The CRISPR/Cas9 system, renowned for its precision in inducing genetic alterations, can target and eliminate specific cancer cells, thereby minimizing off-target effects. Concurrently, immunotherapy, which leverages the immune system's power to combat cancer, has shown promise in treating breast cancer. By integrating these two strategies, we can potentially augment the effectiveness of immunotherapies by knocking out genes that enable cancer cells to evade the immune system. However, safety considerations, such as off-target effects and immune responses, necessitate careful evaluation. Current research endeavors aim to optimize these strategies and ascertain the most effective methods to stimulate the immune response. This review provides novel insights into the integration of CRISPR/Cas9-mediated knockout strategies and immunotherapy, a promising avenue that could revolutionize breast cancer treatment as our understanding of the immune system's interplay with cancer deepens.

The interplay between the tumor cells and their microenvironments is as inseparable as the relationship between "seeds" and "soil." The tumor microenvironments (TMEs) exacerbate malignancy by enriching malignant cell subclones, generating extracellular matrices, and recruiting immunosuppressive cells, thereby diminishing the efficacy of clinical therapies. Modulating TMEs has emerged as a promising strategy to enhance cancer therapy. However, the existing drugs used in clinical settings do not target the TMEs specifically, underscoring the urgent need for advanced strategies. Bioactive materials present unique opportunities for modulating TMEs. Poly(amino acid)s with precisely controllable structures and properties offer exceptional characteristics, such as diverse structural units, excellent biosafety, ease of modification, sensitive biological responsiveness, and unique secondary structures. These attributes hold significant potential for the modulation of TMEs and clinical applications further. Consequently, developing bioactive poly(amino acid)s capable of modulating the TMEs by elucidating structure-activity relationships and mechanisms is a promising approach for innovative clinical oncology therapy. This review summarizes the recent progress of our research team in developing bioactive poly(amino acid)s for multi-modal tumor therapy. First, a brief overview of poly(amino acid) synthesis and their advantages as nanocarriers is provided. Subsequently, the pioneering research of our research group on synthesizing the biologically responsive, dynamically allosteric, and immunologically effective poly(amino acid)s are highlighted. These poly(amino acid)s are designed to enhance tumor therapy by modulating the intracellular, extracellular matrix, and stromal cell microenvironments. Finally, the future development of poly(amino acid)s is discussed. This review will guide and inspire the construction of bioactive poly(amino acid)s with promising clinical applications in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Peptide-Based Structures.

Lenvatinib (LVN) is a potentially effective multiple-targeted receptor tyrosine kinase inhibitor approved for treating hepatocellular carcinoma, metastatic renal cell carcinoma and thyroid cancer. Nonetheless, poor pharmacokinetic properties including poor water solubility and rapid metabolic, complex tumor microenvironment, and drug resistance have impeded its satisfactory therapeutic efficacy. This article comprehensively reviews the uses of nanotechnology in LVN to improve antitumor effects. With the characteristic of high modifiability and loading capacity of the nano-drug delivery system, an active targeting approach, controllable drug release, and biomimetic strategies have been devised to deliver LVN to target tumors in sequence, compensating for the lack of passive targeting. The existing applications and advances of LVN in improving therapeutic efficacy include improving longer-term efficiency, achieving higher efficiency, combination therapy, tracking and diagnosing application and reducing toxicity. Therefore, using multiple strategies combined with photothermal, photodynamic, and immunoregulatory therapies potentially overcomes multi-drug resistance, regulates unfavorable tumor microenvironment, and yields higher synergistic antitumor effects. In brief, the nano-LVN delivery system has brought light to the war against cancer while at the same time improving the antitumor effect. More intelligent and multifunctional nanoparticles should be investigated and further converted into clinical applications in the future.

Severe immunosuppression is a hallmark of colorectal cancer (CRC). Myeloid-derived suppressor cells (MDSCs), one of the most abundant components of the tumor stroma, play an important role in the invasion, metastasis, and immune escape of CRC. MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells, including T and natural killer cells, as well as by inducing the proliferation of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages, which, in turn, promote the growth of cancer cells. Thus, MDSCs are key contributors to the emergence of an immunosuppressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity. In this narrative review, we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment, the current therapeutic approaches and technologies targeting MDSCs, and the therapeutic potential of modulating MDSCs in CRC treatment. This study provides ideas and methods to enhance survival rates in patients with CRC.

Immune checkpoint blockade therapy provides a new strategy for tumor treatment; however, the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects. Herein, we reported a lipid/PLGA nanocomplex (RDCM) co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase (IDO) inhibitor 1MT to improve immunotherapy of colon cancer. Arginine-glycine-aspartic acid (RGD) as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol (PEG), and programmed cell death-ligand 1 (PD-L1) peptide inhibitor DPPA (sequence: CPLGVRGK-GGG-d(NYSKPTDRQYHF)) was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker. The Ce6 and 1MT were encapsulated in PLGA nanoparticles. The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes. When the nanocomplexes were delivered to tumor, DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding. RGD facilitated the cellular internalization of nanocomplexes via avβ3 integrin. Strong immunogenic cell death was induced by 1O2 generated from Ce6 irradiation under 660 nm laser. 1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment. The RDCM facilitated the maturation of dendritic cells, inhibited the activity of IDO, and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice, triggering a robust immunological memory effect, thus effectively preventing tumor metastasis. The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.

The accumulation of reactive oxygen species (ROS) within the bone marrow microenvironment leads to diminished osteogenic differentiation and heightened lipogenic differentiation of mesenchymal stem cells residing in the bone marrow, ultimately playing a role in the development of osteoporosis (OP). Mitigating ROS levels is a promising approach to counteracting OP. In this study, a nanozyme composed of magnesium-based zeolitic imidazolate frameworks (Mg-ZIF) was engineered to effectively scavenge ROS and alleviate OP. The results of this study indicate that Mg-ZIF exhibits significant potential in scavenging ROS and effectively promoting osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Additionally, Mg-ZIF was found to inhibit the differentiation of BMSCs into adipose cells. In vivo experiments further confirmed the ability of Mg-ZIF to mitigate OP by reducing ROS levels. Mechanistically, Mg-ZIF enhances the differentiation of BMSCs into osteoblasts by upregulating lipid metabolic pathways through ROS scavenging. The results indicate that Mg-ZIF has potential as an effective therapeutic approach for the treatment of osteoporosis.

To improve the quality of health in a personalized manner, better control over pharmacologically relevant cargo formulation, organ-specific targeted delivery, and on-demand release of therapeutic agents is crucial. Significant work has been put into designing and developing revolutionary nanotherapeutics approaches for the effective monitoring and personalized treatment of disease. Nanogel (NG) has attracted significant interest because of its tremendous potential in cancer therapy and its environmental stimuli responsiveness. NG is considered a next-generation delivery technology due to its benefits like as size tunability, high loading, stimuli responsiveness, prolonged drug release via in situ gelling mechanisms, stability, and its potential to provide personalized therapy from the investigation of human genes and the genes in various types of cancers and its association with a selective anticancer drug. Stimuli-responsive NGs can be used as smart nanomedicines to detect and treat cancer and can be tuned as personalized medicine as well. This comprehensive review article's major objectives include the challenges of NGs' clinical translation for cancer treatment as well as its early preclinical successes and prospects.

Nanogels open up access to a wide range of applications and offer among others hopeful approaches for use in the field of biomedicine. This review provides a brief overview of current developments of nanogels in general, particularly in the fields of drug delivery, therapeutic applications, tissue engineering, and sensor systems. Specifically, cyclodextrin (CD)-based nanogels are important because they have exceptional complexation properties and are highly biocompatible. Nanogels as a whole and CD-based nanogels in particular can be customized in a wide range of sizes and equipped with a desired surface charge as well as containing additional molecules inside and outside, such as dyes, solubility-mediating groups or even biological vector molecules for pharmaceutical targeting. Currently, biological investigations are mainly carried out in vitro, but more and more in vivo applications are gaining importance. Modern molecular imaging methods are increasingly being used for the latter. Due to an extremely high sensitivity and the possibility of obtaining quantitative data on pharmacokinetic and pharmacodynamic properties, nuclear methods such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) using radiolabeled compounds are particularly suitable here. The use of radiolabeled nanogels for imaging, but also for therapy, is being discussed.

Synthetic polypeptides are biocompatible and biodegradable macromolecules whose composition and architecture can vary over a wide range. Their unique ability to form secondary structures, as well as different pathways of modification and biofunctionalization due to the diversity of amino acids, provide variation in the physicochemical and biological properties of polypeptide-containing materials. In this review article, we summarize the advances in the synthesis of polypeptides and their copolymers and the application of these systems for drug delivery in the form of (nano)particles or hydrogels. The issues, such as the diversity of polypeptide-containing (nano)particle types, the methods for their preparation and drug loading, as well as the influence of physicochemical characteristics on stability, degradability, cellular uptake, cytotoxicity, hemolysis, and immunogenicity of polypeptide-containing nanoparticles and their drug formulations, are comprehensively discussed. Finally, recent advances in the development of certain drug nanoformulations for peptides, proteins, gene delivery, cancer therapy, and antimicrobial and anti-inflammatory systems are summarized.

Breast cancer is one of the most common malignant tumors with high mortality and poor prognosis in women. There is an urgent need to discover new therapeutic targets for breast cancer metastasis. Herein, we identified that Apolipoprotein C1 (APOC1) was up-regulated in primary tumor of breast cancer patient that recurrence and metastasis by immunohistochemistry (IHC). Kaplan-Meier Plotter database showed that high levels of APOC1 in breast cancer patients were strongly associated with worse overall survival (OS) and relapse-free survival (RFS). Mechanistically, APOC1 silencing significantly inhibits MAPK/ERK kinase pathway and restrains the NF-κB to decrease the transcription of target genes related to growth and metastasis in vitro. Based on this regulatory mechanism, we developed these findings into potential therapeutic drugs, glutathione (GSH) responsive nano-particles (NPs) were used for systemic APOC1 siRNA delivery, NPs (siAPOC1) silenced APOC1 expression, and subsequently resulted in positive anti-tumor effects in orthotopic and liver metastasis models in vivo. Taken together, GSH responsive NP-mediated siAPOC1 delivery was proved to be effective in regulating growth and metastasis in multiple tumor models. These findings show that APOC1 could be a potential biomarker to predict the prognosis of breast cancer patients and NP-mediated APOC1 silencing could be new strategies for exploration of new treatments for breast cancer metastasis.

Insufficient tumor accumulation and distribution of immunogenic cell death (ICD) inducer as well as low antitumor immunity severely restrict the therapeutic efficacy of tumor immunotherapy. Tumor associated fibroblasts (TAFs) are important in tumor extracellular matrix (ECM) remodeling and immune evasion. Reprogramming tumor immunosuppressive microenvironment via TAFs regulation might present a promising way for enhanced ICD effect and complete tumor elimination. In this study, TAFs derived tryptase imprinted nanoparticles (DMSN@MIPs) are developed to modulate TAFs and improve tumor immunotherapy effect of doxorubicin liposomes (DOX/LIP). Tryptase (TPS), secreted by mast cells, are found to support tumor growth via transcriptionally activating TAFs to an activated state with increased expression of fibroblast activation marker α-smooth muscle actin (α-SMA). DMSN@MIPs canbe used as artificial antibodies, which effectively neutralize TPS, reduce TAFs activation, promote intra-tumor penetration of DOX/LIP and enhance ICD effect induced by DOX/LIP. In addition, the combined administration system remodels immunosuppressive microenvironment, which not only significantly up-regulates immune cells (DC cells, CD8+T cells, NK cells), but also significantly down-regulates immunosuppressive cells (Treg cells, MDSCs cells). Our results support the DMSN@MIPs canbe a promising approach to improve ICD efficacy in cancer immunotherapy.

Neoplasm (Glioblastoma) and Alzheimer's disease (AD) comprise two of the most chronic psychological ailments. Glioblastoma is one of the aggressive and prevalent malignant diseases characterized by rapid growth and invasion resulting from cell migration and degradation of extracellular matrix. While the latter is characterized by extracellular plaques of amyloid and intracellular tangles of tau proteins. Both possess a high degree of resistance to treatment owing to the restricted transport of corresponding drugs to the brain protected by the blood-brain barrier (BBB). Development of optimized therapies using advanced technologies is a great need of today. One such approach is the designing of nanoparticles (NPs) to facilitate the drug delivery at the target site. The present article elaborates the advances in nanomedicines in treatment of both AD as well as Gliomas. The intention of this review is to provide an overview of different types of NPs with their physical properties emphasizing their importance in traversing the BBB and hitting the target site. Further, we discuss the therapeutic applications of these NPs along with their specific targets. Multiple overlapping factors with a common pathway in development of AD and Glioblastoma are discussed in details that will assist the readers in developing the conceptual approach to target the NP for an aging population in the given circumstances with limitations of currently designed NPs, and the challenges to meet and the future perspectives.

Tumor-associated macrophages (TAMs)-based immunotherapy is a promising strategy. Since TAMs are mainly composed of M2-type macrophages, they have a promoting effect on tumor growth, invasion, and metastasis. M2-type macrophages contain a specific receptor CD163 on their surface, providing a prerequisite for active targeting to TAMs. In this study, we prepared CD163 monoclonal antibody modified doxorubicin-polymer prodrug nanoparticles (abbreviated as mAb-CD163-PDNPs) with pH responsiveness and targeted delivery. First, DOX was bonded with the aldehyde group of a copolymer by Schiff base reaction to form an amphiphilic polymer prodrug, which could self-assemble into nanoparticles in the aqueous solution. Then, mAb-CD163-PDNPs were generated through a "Click" reaction between the azide group on the surface of the prodrug nanoparticles and dibenzocyclocytyl-coupled CD163 monoclonal antibody (mAb-CD163-DBCO). The structure and assembly morphology of the prodrug and nanoparticles were characterized by ¹H NMR, MALDI-TOF MS, FT-IR UV-vis spectroscopy, and dynamic light scattering (DLS). In vitro drug release behavior, cytotoxicity, and cell uptake were also investigated. The results show that the prodrug nanoparticles have regular morphology and stable structure, especially mAb-CD163-PDNPs, which can actively target TAMs at tumor sites, respond to the acidic environment in tumor cells, and release drugs. While depleting TAMs, mAb-CD163-PDNPs can actively enrich drugs at the tumor site and have a strong inhibitory effect on TAMs and tumor cells. The result of the in vivo test also shows a good therapeutic effect, with a tumor inhibition rate of 81%. This strategy of delivering anticancer drugs in TAMs provides a new way to develop targeted drugs for immunotherapy of malignant tumors.

Cancer immunotherapy has become one of the current research hotspots. However, the deficiencies including restricted immunogenicity, insufficient antigen presentation, and low responsive rate limited their therapeutic applications. Own to the small size and excellent biocompatibility, carbon dots (CDs) can serve as nanovectors to improve the efficacy of cancer immunotherapy. Herein, a tumor antigen-based nanovaccines (GMal+B16F10-Ag and GMal+CT26-Ag) by the conjugation of CDs with the tumor cell-derived antigens (B16F10-Ag and CT26-Ag) is constructed. These nanovaccines can be effectively taken up by dendritic cells (DC2.4), promote DC cell maturation, cross-present the antigen to T cells, specifically target B16F10 melanoma or CT26 colon cancers, and inhibit tumor growth distinctly. This work illustrates the promise of CDs acting as versatile carriers for antigen delivery to achieve the optimal immunotherapeutic outcomes.

The complexity of the tumor microenvironment (TME) severely hinders the therapeutic effects of various cancer treatment modalities. The TME differs from normal tissues owing to the presence of hypoxia, low pH, and immune-suppressive characteristics. Modulation of the TME to reverse tumor growth equilibrium is considered an effective way to treat tumors. Recently, polymeric nanomedicines have been widely used in cancer therapy, because their synthesis can be controlled and they are highly modifiable, and have demonstrated great potential to remodel the TME. In this review, we outline the application of various stimuli responsive polymeric nanomedicines to modulate the TME, aiming to provide insights for the design of the next generation of polymeric nanomedicines and promote the development of polymeric nanomedicines for cancer therapy.

Glioblastoma multiforme (GBM) is the most malignant brain tumor with high mortality. Knowledge of the stemness concept has developed recently, giving rising to a novel hallmark with therapeutic potential that can help in management of GBM recurrence and prognosis. However, limited blood-brain barrier (BBB) penetration, non-discriminatory distribution, and deficiency of diagnosis remain three major obstacles need to be overcome for further facilitating therapeutic effects. Herein, D4F and α-Melittin (a-Mel) are co-assembled to construct bio-fabricated nanoplatforms, which endowed with inherent BBB permeability, precise tumor accumulation, deep penetration, and immune activation. After carrying arsenic trioxide (ATO) and manganese dichloride (MnCl₂), these elaborated nanodrugs, Mel-LNPs/MnAs, gather in tumor foci by natural pathways and respond to microenvironment to synchronously release Mn²⁺ and As³⁺, achieving real-time navigating-diagnosis and tumor cell proliferation inhibition. Through down regulating CD44 and CD133 expression, the GBM stemness was suppressed to overcome its high recurrence, invasion, and chemoresistance. After being combined with temozolomide (TMZ), the survival rate of GBM-bearing mice is significantly enhanced, and the rate of recurrence is powerfully limited. Collectively, this tumor-specific actuating multi-modality nanotheranostics provide a promising candidate for clinical application with high security.

Dendrimers have numerous applications in imaging and drug delivery. Designing a dendrimer diagnostic platform with a well-defined structure and controlled drug delivery is a formidable challenge. Here, we design dendritic polymer-platinum conjugates (G5-PEG-Pt) as pH-responsive nanovesicles for imaging-guided platinum drug delivery. The G5-PEG-Pt have a well-defined structure, intrinsically bright fluorescence, and acid-responsive drug release. The pH-responsive G5-PEG-Pt could rapidly release the platinum drug at acidic pH (5.0) than neutral pH (7.4). The G5-PEG-Pt could enter SKOV-3 human ovarian cancer cells by the endocytosis pathway and exhibited comparative cytotoxicity to free cisplatin. By virtue of the prolonged blood circulation time and the enhanced permeability and retention (EPR) effect, a 4.4-fold higher tumor platinum uptake than that of free cisplatin was achieved, potentially enhancing the therapeutic indexes of the platinum drug. Therefore, these pH-responsive platinum and fluorescent dendrimer conjugates are expected to be potent in vivo cancer optical imaging and therapy platforms.

Nasopharyngeal carcinoma (NPC) is a serious and highly invasive epithelial malignancy that is closely associated with Epstein-Barr virus (EBV). Due to the lack of therapeutic vaccines for NPC, we selected EBV latent membrane protein 2 (LMP2) as a preferable targeting antigen to develop a lipid-based LMP2-mRNA (mLMP2) vaccine. Full-length mLMP2 expressing LMP2 was first synthesized using an in vitro transcription method and then encapsulated into (2,3-dioleacyl propyl) trimethylammonium chloride (DOTAP)-based cationic liposomes to obtain the mRNA vaccine (LPX-mLMP2). The cell assays showed that the antigen-presenting cells were capable of highly efficient uptake of LPX-mLMP2 and expression of LMP2. LMP2 could subsequently be presented to form the peptide-major histocompatibility complex (pMHC). Furthermore, LPX-mLMP2 could accumulate in the spleen, express antigens, promote the maturation of dendritic cells and stimulate antigen-specific T-cell responses in vivo. It dramatically inhibited the tumor growth of the LMP2-expressing tumor model after three doses of vaccination. Additionally, the proliferation of antigen-specific T cells in the tumor site made a good sign for the promise of mRNA vaccines in virus-induced cancer. Overall, we provided a newly developed antigen-encoding mRNA vaccine with advantages against NPC. We also demonstrated that mRNA vaccines are attractive candidates for cancer immunotherapy.

Supplementary material (methods of cytotoxicity assay, LMP2 expression, hemolysis test, the results of purity and maturity of BMDCs, LMP2 expression, and evaluation of T cells in lymph nodes and gating strategy for CTLs) is available in the online version of this article at 10.1007/s12274-022-5254-x.

Anti-PD(L)1 immunotherapy recently arises as an effective treatment against triple-negative breast cancer (TNBC) but is only applicable to a small portion of TNBC patients due to the low PD-L1 expression and the immunosuppressive tumor microenvironment (TME). To address these challenges, a multifunctional "drug-like" copolymer that possesses the auto-changeable upper critical solution temperature and the capacity of scavenging reduced nicotinamide adenine dinucleotide phosphate (NADPH) inside tumor cells is synthesized and employed to develop a hypoxia-targeted and BMS202 (small molecule antagonist of PD-1/PD-L1 interactions)-loaded nanomedicine (BMS202@HZP NPs), combining the anti-PD-L1 therapy and the low-dose radiotherapy (LDRT) against TNBC. In addition to the controlled release of BMS202 in the hypoxic TNBC, BMS202@HZP NPs benefit the LDRT by upregulating the pentose phosphate pathway (PPP, the primary cellular source for NADPH) of TME whereas scavenging the NADPH inside tumor cells. As a result, the BMS202@HZP NPs-mediated LDRT upregulate the PD-L1 expression of tumor to promote anti-PD-L1 therapy response while reprogramming the immunometabolism of TME to alleviate its immunosuppression. This innovative nanomedicine-mediated radio-immunometabolism regulation provides a promising strategy to reinforce the anti-PD-L1 therapy against TNBC.

As one of the most cutting-edge and promising polymer crosslinked network nanoparticle systems. Polymer nano-sized hydrogels (nanogels) have been a hot topic in the biomedical field over the last few decades. Due to their unique characteristics, which include their relatively high drug encapsulation efficiency, ease of preparation, high tunability, low toxicity, high stability in serum and responsive behavior to a range of stimuli to facilitate drug release. Nanogels are thought to be the next generation of drug delivery systems that can completely change the way that drug delivery systems have an impact on patients' lives. Nanogels have demonstrated significant potential in a variety of fields, including chemotherapy, diagnosis, organ targeting, and delivery of bioactive molecules of different dimensions. However, the lack of substantial clinical data from nanogels becomes one of the major barriers to translating the nanogel concept into a practical therapeutic application for many disease conditions. In addition, nanogel safety profiles have been the major concern that hinders it advancement to the clinical trial phase. This review aims to emphasize the unique properties of nanogels as delivery systems for a variety of bioactive molecules over other nano-delivery systems. Also, this review attempts to give insight into the recent progress in nanogels as a carrier in the field of nanomedicine to overcome complex biological barriers. Relevant scientific data and clinical rationale for the development and the potential use of nanogel as a carrier for targeted therapeutic interventions are discussed. Finally, the concluding points of this review highlight the importance of understanding the long-term toxicity profile of nanogel within the biological system to fully understand their biocompatibility.

For cancer immunotherapy, triggering toll-like receptors (TLRs) in dendritic cells (DCs) can potentiate antigen-based immune responses. Nevertheless, to generate robust and long-lived immune responses, a well-designed nanovaccine should consider different locations of TLRs on DCs and co-deliver both antigens and TLR agonist combinations to synergistically induce optimal antitumor immunity. Herein, we fabricated lipid-polymer hybrid nanoparticles (LPNPs) to spatio-temporally deliver model antigen ovalbumin (OVA) on the surface of the lipid layer, TLR4 agonist monophosphoryl lipid A (MPLA) within the lipid layer, and TLR7 agonist imiquimod (IMQ) in the polymer core to synergistically activate DCs by both extra- and intra-cellular TLRs for enhancing adaptive immune responses. LPNPs-based nanovaccines exhibited a narrow size distribution at the mean diameter of 133.23 nm and zeta potential of -2.36 mV, showed a high OVA loading (around 70.83 μg/mg) and IMQ encapsulation efficiency (88.04%). Our data revealed that LPNPs-based nanovaccines showed great biocompatibility to immune cells and an excellent ability to enhance antigen internalization, thereby promoting DCs maturation and cytokines production. Compared to Free OVA, OVA-LPNPs promoted antigen uptake, lysosome escape, depot effect and migration to secondary lymphatic organs. In vivo immunization showed that IMQ-MPLA-OVA-LPNPs with dual agonists induced more powerful cellular and humoral immune responses. Moreover, prophylactic vaccination by IMQ-MPLA-OVA-LPNPs effectively suppressed tumor growth and increased survival efficacy. Hence, the nanovaccines we fabricated can effectively co-deliver antigens and different TLR agonists and realize coordinated stimulation of DCs in a spatio-temporal manner for enhanced immune responses, which provides a promising strategy for cancer immunotherapy.

Polypeptide-based nanoparticles are one of the promising excipients of nanomedicines due to their excellent biosafety and flexible modification. Among all the types of polypeptide nanoparticles, polycystine (PCys2)-based ones draw increasing attention due to their unique properties. On the one hand, the uniformed nanogels can be easily obtained through the crosslinking of two active centers during polymerization without additional step of self-assembly. On the other hand, the Cys2-based nanoparticles always showed reduction-responsiveness owing to the inherent disulfide bond. With the development of advanced diagnostic and therapeutic technologies, the multi-functional PCys2-based nanoparticles were achieved via rational construction of the polymer structure. This review summarizes the overall development of Cys2-based polypeptide nanoparticles, especially the structural design for the generation of multi-functional nanoparticles, along with their corresponding biomedical applications.

Gastrointestinal cancer (GIC) is a common malignant tumour of the digestive system that seriously threatens human health. Due to the unique organ structure of the gastrointestinal tract, endoscopic and MRI diagnoses of GIC in the clinic share the problem of low sensitivity. The ineffectiveness of drugs and high recurrence rates in surgical and drug therapies are the main factors that impact the curative effect in GIC patients. Therefore, there is an urgent need to improve diagnostic accuracies and treatment efficiencies. Nanotechnology is widely used in the diagnosis and treatment of GIC by virtue of its unique size advantages and extensive modifiability. In the diagnosis and treatment of clinical GIC, surface-enhanced Raman scattering (SERS) nanoparticles, electrochemical nanobiosensors and magnetic nanoparticles, intraoperative imaging nanoparticles, drug delivery systems and other multifunctional nanoparticles have successfully improved the diagnosis and treatment of GIC. It is important to further improve the coordinated development of nanotechnology and GIC diagnosis and treatment. Herein, starting from the clinical diagnosis and treatment of GIC, this review summarizes which nanotechnologies have been applied in clinical diagnosis and treatment of GIC in recent years, and which cannot be applied in clinical practice. We also point out which challenges must be overcome by nanotechnology in the development of the clinical diagnosis and treatment of GIC and discuss how to quickly and safely combine the latest nanotechnology developed in the laboratory with clinical applications. Finally, we hope that this review can provide valuable reference information for researchers who are conducting cross-research on GIC and nanotechnology.

As a representative strategy for cancer immunotherapy, cancer nanovaccines have aroused enormous interest. Although various nanovaccines have been developed to promote immunogenicity and improve the therapeutic efficacy, chiral nanovaccines have been less explored as of yet. Chiral carbon dots (CDs) have similar size to proteins, abundant functional groups, and nanoscale chirality, which can not only carry and deliver antigens but also induce cellular and humoral immune responses and can play dual roles of nanovehicles and immune adjuvants. Herein, we demonstrate that the chiral nanovaccines (l/d-OVA) could be conveniently fabricated by utilizing chiral CDs as carriers and immune adjuvants and ovalbumin (OVA) as an antigen model. l/d-OVA nanovaccines could be effectively internalized by mouse bone-marrow-derived dendritic cells (BMDCs), boost BMDC maturation, efficiently cross-present to T cells, and suppress the growth of B16-OVA melanoma. This work illustrates the hopeful potential of chiral CDs as effective vectors for loading protein cargos and delivering them into cancer cells.

Indoleamine 2,3-dioxygenase (IDO), with an immunoregulatory effect related to tryptophan metabolism, has emerged as an attractive target for cancer immunotherapy. Here, a polymeric IDO inhibitor based on the poly(ethylene glycol)-b-poly(L-tyrosine-co-1-methyl-D-tryptophan) copolymer (PEG-b-P(Tyr-co-1-MT)) was developed for facile trident cancer immunotherapy. PEG-b-P(Tyr-co-1-MT) could self-assemble into nanoparticles (NPs), which were subject to enzyme degradation and capable of retarding the metabolism of L-tryptophan (TRP) to L-kynurenine (KYN) in B16F10 cancer cells. Notably, cRGD-functionalized NPs showed efficient encapsulation and an enzyme-responsive release of doxorubicin (DOX) and the BET bromodomain inhibitor JQ1. DOX in drug-loaded nanoparticles (cRGD-NPDJ) could activate immunization by inducing the discernible immunogenic cell death (ICD) of cancer cells and promoting the secretion of interferon-γ (IFN-γ), which besides activating the antitumor cellular immunity often upregulates the expression of PD-L1 and IDO to accelerate tumor progression. The encapsulated JQ1 and polymeric 1-MT in cRGD-NPDJ could reverse the expression by disrupting the binding of BET proteins with chromatin and elevating the TRP/KYN ratio. In B16F10 tumor-bearing C57BL/6 mice, cRGD-NPDJ displayed significantly increased CD8⁺ T cells, matured dendritic cells (mDCs), and cytokines (IFN-γ, TNF-α), as well as reduced regulatory T cells and downregulated PD-L1 expression at tumor sites, generating immune cascade reactions and a distinct improvement of the tumor microenvironment (TME), leading to significant tumor suppression and survival prolongation. The polymeric IDO inhibitor provides a facile strategy for the co-delivery of chemotherapeutics and inhibitors for efficient and safe combination cancer immunotherapy.

The combined delivery of chemotherapeutics with checkpoint inhibitors of the PD-1/PD-L1 pathway provides a new approach for cancer treatment. Small-molecule peptide inhibitors possess short production cycle, low immunogenicity, and fewer side effects; however, their potential in cancer therapy is hampered by the rapid biodegradation and a nanocarrier is needed for efficient drug delivery. Herein, anticancer drug doxorubicin (DOX) and PD-L1 inhibitor peptide P-12 are co-loaded by a lipid polymer nanocomplex based on poly(lactic-co-glycolic acid) (PLGA) and DSPE-PEG. Octaarginine (R8)-conjugated DSPE-PEG renders the LPN efficient internalization by cancer cells. The optimal nanomedicine LPN-30-R8^2K@DP shows a diameter of 125 nm and a DOX and P-12 loading content of 5.0 and 6.2%, respectively. LPN-30-R8^2K@DP exhibits good physiological stability and enhanced cellular uptake by cancer cells. It successfully induces immunogenic cell death and PD-L1 blockade in CT26 cancer cells. The in vivo antitumor study further suggests that co-loaded nanomedicine efficiently suppresses CT26 tumor growth and elicits antitumor immune response. This study manifests that lipid polymer nanocomplexes are promising drug carriers for the efficient chemo-immunotherapy of cancer.

Recently, the role of starch-based carrier systems in anticancer drug delivery has gained considerable attention. Although there are same anticancer drugs, difference in their formulations account for unique therapeutic effects. However, the exploration on the effect-enhancing of anticancer drugs and their loading system by modified starch from the perspective of carrier regulation is still limited. Moreover, research on the reduced toxicity of the anticancer drugs due to modified starch as the drug carrier mediated by the intestinal microenvironment is lacking, but worth exploring. In this review, we examined the effect of modified starch on the loading and release properties of anticancer drugs, and the effect of resistant starch and its metabolites on intestinal microecology during inflammation. Particularly, the interactions between modified starch and drugs, and the effect of resistant starch on gene expression, protein secretion, and inflammatory factors were discussed. The findings of this review could serve as reference for the development of anticancer drug carriers in the future.

The conventional cancer therapeutic modalities include surgery, chemotherapy and radiotherapy. Although immunotherapy and targeted therapy are also widely used in cancer treatment, chemotherapy remains the cornerstone of tumor treatment. With the rapid development of nanotechnology, nanomedicine is believed to be an emerging field to further improve the efficacy of chemotherapy. Until now, there are more than 17 kinds of nanomedicine for cancer therapy approved globally. Thereinto, conjugated nanomedicine, as an important type of nanomedicine, can not only possess the targeted delivery of chemotherapeutics with great precision but also achieve controlled drug release to avoid adverse effects. Meanwhile, conjugated nanomedicine provides the platform for combining several different therapeutic approaches (chemotherapy, photothermal therapy, photodynamic therapy, thermodynamic therapy, immunotherapy, etc.) with the purpose of achieving synergistic effects during cancer treatment. Therefore, this review focuses on conjugated nanomedicine and its various applications in synergistic chemotherapy. Additionally, the further perspectives and challenges of the conjugated nanomedicine are also addressed, which clarifies the design direction of a new generation of conjugated nanomedicine and facilitates the translation of them from the bench to the bedside.

Controllable nano-assembly with stimuli-responsive groups is emerging as a powerful strategy to generate theranostic nanosystems that meet unique requirements in modern medicine. However, this prospective field is still in a proof-of-concept stage due to the gaps in our understanding of complex-(nano-assemblies)-complex-(biosystems) interactions. Indeed, stimuli-responsive assembly-disassembly is, in and of itself, a process of nano-bio interactions, the key steps for biological fate and functional activity of nano-assemblies. To provide a comprehensive understanding of these interactions in this review, we first propose a 4W1H principle (Where, When, What, Which and How) to delineate the relevant dynamic biological processes, behaviour and fate of nano-assemblies. We further summarize several key parameters that govern effective nano-bio interactions. The effects of these kinetic parameters on ADMET processes (absorption, distribution, metabolism, excretion and transformation) are then discussed. Furthermore, we provide an overview of the challenges facing the evaluation of nano-bio interactions of assembled nanodrugs. We finally conclude with future perspectives on safe-by-design and application-driven-design of nano-assemblies. This review will highlight the dynamic biological and physicochemical parameters of nano-bio interactions and bridge discrete concepts to build a full spectrum understanding of the biological outcomes of nano-assemblies. These principles are expected to pave the way for future development and clinical translation of precise, safe and effective nanomedicines with intelligent theranostic features.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

Tumor microenvironment responsive nanomedicine has drawn considerable attention for combination therapy, but still remains a significant challenge for less side effects and enhanced anti-tumor efficiency. Herein, we develop a pH/ROS dual-responsive supramolecular polypeptide nanoprodrug (PFW-DOX/GOD) by using pillar[5]arene-based host-guest strategy for combined glucose degradation, chemodynamic therapy (CDT), and chemotherapy (CT). The PFW-DOX/GOD consists of a pH-responsive ferrocene/pillar[5]arene-containing polypeptide, a ROS-responsive polyprodrug, and encapsulated glucose oxidase (GOD). Upon into intracellular acidic environment, PFW-DOX/GOD exhibits rapid pH-triggered disassembly behavior. Simultaneously, the released GOD can catalyze intratumoral glucose into massive H₂O₂, which are further converted into highly toxic hydroxyl radicals (•OH) by the catalysis of ferrocene via the Fenton reaction. Thereafter, induced by the ROS-responsive cleavage of thioketal linkage, the conjugated DOX prodrug was released and activated. The combined glucose degradation, chemodynamic therapy (CDT), and chemotherapy (CT) of PFW-DOX/GOD present anti-tumor effect with 96% of tumor inhibitory rate (TIR). Therefore, such tumor microenvironment-responsive supramolecular polypeptide nanoprodrugs represent a potential candidate for combination therapy with minimal side effects. STATEMENT OF SIGNIFICANCE: In this work, a tumor microenvironment-responsive supramolecular polypeptide nanoprodrug (PFW-DOX/GOD) was prepared via pillar[5]arene-based host-guest interactions, and presented low side effects and high tumor accumulation owing to the diameters of about 200 nm and surface PEG segment. After pH-responsive release of GOD in the intracellular acidic environment, the cascade catalytic reactions including GOD-catalyzed degradation of intratumoral glucose and Fenton reaction, effectively happened to generate •OH for chemodynamic therapy (CDT), which subsequently induced the cleavage of thioketal linkage to activate free DOX for chemotherapy (CT). Collectively, this supramolecular polypeptide nanoprodrugs provide a promising strategy for combination therapy with synergetic anti-tumor effect.

Recent years have witnessed increasingly rapid advances in nanocarrier-based biomedicine aimed at improving treatment paradigms for cancer. Nanogels serve as multipurpose and constructed vectors formed via intramolecular cross-linking to generate drug delivery systems, which is attributed predominantly to their satisfactory biocompatibility, bio-responsiveness, high stability, and low toxicity. Recently, immunotherapy has experienced unprecedented growth and has become the preferred strategy for cancer treatment, and mainly involves the mobilisation of the immune system and an enhanced anti-tumour immunity of the tumour microenvironment. Despite the inspiring success, immunotherapeutic strategies are limited due to the low response rates and immune-related adverse events. Like other nanomedicines, nanogels are comparably limited by lower focal enrichment rates upon introduction into the organism via injection. Because nanogels are three-dimensional cross-linked aqueous materials that exhibit similar properties to natural tissues and are structurally stable, they can comfortably cope with shear forces and serum proteins in the bloodstream, and the longer circulation life increases the chance of nanogel accumulation in the tumour, conferring deep tumour penetration. The large specific surface area can reduce or eliminate off-target effects by introducing stimuli-responsive functional groups, allowing multiple physical and chemical modifications for specific purposes to improve targeting to specific immune cell subpopulations or immune organs, increasing the bioavailability of the drug, and conferring a low immune-related adverse events on nanogel therapies. The slow release upon reaching the tumour site facilitates long-term awakening of the host's immune system, ultimately achieving enhanced therapeutic effects. As an effective candidate for cancer immunotherapy, nanogel-based immunotherapy has been widely used. In this review, we mainly summarize the recent advances of nanogel-based immunotherapy to deliver immunomodulatory small molecule drugs, antibodies, genes and cytokines, to target antigen presenting cells, form cancer vaccines, and enable chimeric antigen receptor (CAR)-T cell therapy. Future challenges as well as expected and feasible prospects for clinical treatment are also highlighted.

Agents for tumor vascular infarction are recently developed therapeutic agents for the vascular destruction of tumors. They can suppress the progression of the tumor by preventing the flow of nutrition and oxygen to its tissues. Agents of tumor vascular infarction can be divided into three categories according to the differences in their pathways of action: those that use the thrombin-activating pathway, fibrin-activating pathway, and platelet-activating pathway. However, poor targeting ability, low permeation, and potential side-effects restrict the development of the corresponding drugs. Biomaterials can subtly avoid these drawbacks to suppress the tumor. In this article, the authors summarize currently used biomaterials for tumor infarction therapy with the goal of identifying its mechanism, and discuss outstanding deficiencies in methods of this kind.

Many nanocarriers have been developed to react physicochemically to exterior stimuli like ultrasonic, light, heat, and magnetic fields, along with various internal stimuli including pH, hypoxia, enzyme, and redox potential. Nanocarriers are capable to respond various stimuli within the cancer cells to enable on-demand drug delivery, activation of bioactive compounds, controlled drug release, and targeting ligands, as well as size, charge, and conformation conversion, enabling sensing and signaling, overcoming multidrug resistance, accurate diagnosis, and precision therapy.

Carbohydrates are ubiquitous biomolecules with a high proclivity for supramolecular network formation. Numerous carbohydrate-based nanomaterials have been used in biological solicitations and stimuli-based responses. Particular emphasis has been placed on the utilization of carbohydrate-based NPs and nanogels in various fields including imaging, drug administration, and tissue engineering. Because the assembly process is irreversible, carbohydrate-based systems are excellent ingredients for the development of stimulus-responsive nanocarriers for cancer-targeted chemotherapy. This review aims to summarise current research on carbohydrate-based nanomaterials, with an emphasis on stimuli-sensitive nanocarriers for cancer-targeted chemotherapy.

Carbohydrates-based stimulus-responsive nanomaterials have been proved highly efficient for targeted delivery of anticancer drugs, thus leading to effective chemotherapy with minimum off-target effects.